phenylephrine-hydrochloride and Hair-Diseases

Trichorhinophalangeal syndrome (TRPS) is a rare multisystem disorder characterized by abnormalities in the hair (tricho), nose (rhino), and digits (phalangeal). A variety of nonspecific intraoral findings have been reported in the literature, including hypodontia, delayed tooth eruption, malocclusion, a high-arched palate, mandibular retrognathia, midface hypoplasia, and multiple impacted teeth. In addition, supernumerary teeth have been detected in several persons with TRPS, especially type 1. This report describes the clinical manifestations and dental management of a TRPS 1 patient with multiple impacted supernumerary and permanent teeth.. A 15-year-old female patient visited our clinic with a known medical history of TRPS 1 with laceration of the tongue caused by teeth eruption in the palate.. Radiographic images showed a total of 45 teeth: two deciduous, 32 permanent, and 11 supernumerary teeth. Six permanent teeth and 11 supernumerary teeth in the posterior quadrants were impacted. Four impacted third molars, supernumerary teeth, retained deciduous teeth, and impacted maxillary premolars were removed under general anaesthesia.. This case suggests that all patients with TRPS should undergo full clinical and radiographic oral examination and should be informed about the disease and the importance of dental counselling.

Topics: Adolescent; Female; Hair Diseases; Humans; Langer-Giedion Syndrome; Nose; Tooth, Impacted; Tooth, Supernumerary

Trichorhinophalangeal syndrome (TRPS) is a rare autosomal dominant disorder caused by defects involving the TRPS1 gene. It exhibits distinctive craniofacial, ectodermal and skeletal abnormalities, such as sparse hair, bulbous nasal tip and short deformed fingers, with extremely variable expressivity.. We report the case of a 17 months old girl, who presented growth retardation and dysmorphic features. Postnatal growth was always below - 2 Standard Deviation for both weight and length and physical examination revealed relative macrocephaly, sparse hair, bulbous nasal tip, thin upper lip, protruding ears, prominent forehead, small jaw, and short hands and feet. Patient's mother shared the same facial features, and presented sparse hair and small hands. The maternal grandfather and two uncles presented short stature, bulbous nasal tip, thin hair, and premature alopecia. Molecular analysis of TRPS1 gene showed a heterozygous c.2086C > T;(p.Arg696Ter) mutation both in the patient and her mother, confirming the diagnosis of TRPS, type I.. Clinical phenotype of TRPS can be subtle and the syndrome often remains undiagnosed. A comprehensive clinical examination and an exhaustive family history are crucial to reach the correct diagnosis, which is essential to perform adequate follow-up and timely therapeutic procedures.

Topics: DNA-Binding Proteins; Early Diagnosis; Female; Fingers; Hair Diseases; Heterozygote; Humans; Infant; Langer-Giedion Syndrome; Mutation; Nose; Repressor Proteins; Transcription Factors

A Thai mother and her two daughters were affected with tricho-rhino-phalangeal syndrome type I. The daughters had 15 and 18 supernumerary teeth, respectively. The mother had normal dentition. Mutation analysis of TRPS1 showed a novel heterozygous c.3809_3811delACTinsCATGTTGTG mutation in all. This mutation is predicted to cause amino acid changes in the Ikaros-like zinc finger domain near the C-terminal end of TRPS1, which is important for repressive protein function. The results of our study and the comprehensive review of the literature show that pathways of forming supernumerary teeth appear to involve APC and RUNX2, the genes responsible for familial adenomatous polyposis syndrome and cleidocranial dysplasia, respectively. The final pathway resulting in supernumerary teeth seems to involve Wnt, a morphogen active during many stages of development. © 2016 Wiley Periodicals, Inc.

Topics: Adult; DNA Mutational Analysis; DNA-Binding Proteins; Facies; Female; Fingers; Genetic Association Studies; Hair Diseases; Heterozygote; Humans; Langer-Giedion Syndrome; Middle Aged; Models, Biological; Mutation; Nose; Phenotype; Radiography; Repressor Proteins; Tooth, Supernumerary; Transcription Factors

Alopecia present from birth includes a broad differential diagnosis and often represents a diagnostic and therapeutic challenge for the involved physician.. An initial correct diagnosis and classification is essential because structural hair defects may be the expression of a genetic disorder affecting hair growth, part of a congenital syndrome with accompanying hair malformations, or a marker for an underlying metabolic disorder and may impact the mental and physical development of a child. Pathological hair loss rarely occurs in the first year of life; however, it may be a leading symptom of many congenital diseases.. In recent years, the clinical and microscopic features of hereditary hair shaft disorders have been characterized and classified. Furthermore, significant progress has been made in our knowledge of genes that control the normal development and differentiation of hair follicles, and thus the research is to define and classify the hair disorders within a genetic basis.. In this article we discuss several types of genotrichosis and provide a practical classification based on their clinical features.

Topics: Alopecia; Aneurysm; Carcinoma, Basal Cell; Child; Cleft Lip; Cleft Palate; Deafness; Ectodermal Dysplasia; Eczema; Facies; Fingers; Growth Disorders; Hair Diseases; Hallermann's Syndrome; Histiocytoma, Benign Fibrous; Humans; Hypotrichosis; Ichthyosis; Intellectual Disability; Keratitis; Langer-Giedion Syndrome; Microcephaly; Nose; Skin Diseases, Genetic; Skin Neoplasms

We report a case of an extremely rare histologic combination of pilomatrix or pilomatrical carcinoma with admixed melanocytes within the same tumor mass. Pilomatrix carcinoma is a neoplasm of low-grade malignancy that is characterized by a tendency for recurrence but low risk of metastasis. A 77-year-old male presented with a nodule on the bridge of the nose that was excised. Histologically, it was typified by asymmetry and poor circumscription, the presence of several variably sized and shaped basaloid aggregations, and surface ulceration. The tumors were composed of pleomorphic basaloid cells with prominent nucleoli and frequent mitoses (some of which were atypical) accompanied by central areas with keratotic material, shadow cells, and foci of necrosis. In addition, intermingled with the pilomatrix carcinoma, several easily identified pigmented cells with dendritic processes were present singly and as small aggregates. There was no atypia associated with the melanocytic component. Immunohistochemistry revealed the CK14 to be positive mainly within the keratinizing and the squamous epithelial elements of the tumor. The melanocytic component was strongly immunoreactive for S100, melanoma cocktail (HMB45 and Melan-A), and microphthalmia transcription factor. Pilomatrix carcinoma with melanocytes should be distinguished from the conventional pilomatrixoma with pigmentation, melanocytic matricoma, melanoma, and pigmented basal cell carcinoma with matrical differentiation. Clinicians and pathologists should be aware of the occurrence of pilomatrix carcinoma with melanocytes because of its potential for diagnosis as melanoma. This peculiar lesion recapitulates the intimate relationship existing between matrical epithelium and melanocytes in the embryonal hair follicle or in the anagen stage of the hair cycle. It is possible that sun damage played a role in stimulating migration of melanocytes among matrical cells in this case.

Topics: Aged; Biopsy, Needle; Carcinoma, Skin Appendage; Diagnosis, Differential; Follow-Up Studies; Hair Diseases; Humans; Immunohistochemistry; Male; Melanocytes; Neoplasm Staging; Nose; Pilomatrixoma; Risk Assessment; Skin Neoplasms; Treatment Outcome

Trichostasis spinulosa (TS) is a common disorder of hair follicle, characterized by spinous plugs. Topical treatments offer temporary relief but permanent removal of the abnormal follicles using hair removal lasers may result in a definite cure.. To evaluate the safety and efficacy of 755-nm alexandrite laser for the treatment of TS lesions.. Two consecutive 755-nm alexandrite laser treatments were performed one month apart. The clinical response and adverse effects were assessed four weeks after the first and second treatments and 20 weeks after the second treatment.. Thirty one patients with skin phototypes II to IV completed the study. At the last follow up visit, a decrease in dark-plug density of greater than 50% was noted in 16 patients (51.3%), while only three patients (9.7%) had an improvement of greater than 75%. Ten of the 21 patients (47.6%) with skin type III and six of the seven patients (85.7%) with skin type IV achieved at least 50% improvement in lesions at the last follow up visit (P = 0.1).. The 755-nm alexandrite laser can safely and effectively reduce TS lesions lasting for a relatively long time in patients with skin types III-IV.

Topics: Adolescent; Adult; Female; Follow-Up Studies; Hair Diseases; Hair Follicle; Hair Removal; Humans; Iran; Laser Therapy; Lasers, Solid-State; Male; Middle Aged; Nose; Patient Satisfaction; Remission Induction; Treatment Outcome; Young Adult

Spindle cell-predominant trichodiscoma (SCPT) is a benign adnexal neoplasm, best categorized within the trichodiscoma-fibrofolliculoma continuum. SCPTs clinically present as dome-shaped papules usually on the face, particularly on the nose or the nasolabial fold. The SCPT variant has been described as a particularly cellular trichodiscoma composed of small interweaving fascicles and sheets of spindle cells. Identical lesions were previously referred to as neurofollicular hamartomas because of their predominantly fascicular stromal cellularity and focal S100 positivity. In this article, we report a rare variant of SCPT with a palisaded arrangement. The patient is a middle-aged man with no significant dermatologic history who presented with a skin-colored papule on the left nasal ala. It had been present for approximately 10 years with only minimal growth over that time. A biopsy was obtained. Histopathological analysis revealed a dermal papule composed of bland spindle cells arranged in a striking palisading pattern within a fibromyxoid stroma with associated peripheral hyperplasia of sebaceous glands. The palisaded pattern shared features reminiscent of Verocay bodies of a schwannoma. Immunohistochemical studies revealed stromal spindled cells with a strong and diffuse pattern of CD34 expression and absent S100 and SOX10 expressions. To our knowledge, only 2 cases of SCPT with a palisaded pattern have been presented. SCPT with a palisaded pattern is a rare histopathologic variant that may resemble a schwannoma but can be recognized by its strong epithelial components and immunohistochemical staining pattern.

Topics: Hair Diseases; Humans; Male; Middle Aged; Neurilemmoma; Nose; Sebaceous Glands; Skin Neoplasms

Skeletal disorders, including both isolated and syndromic brachydactyly type E, derive from genetic defects affecting the fine tuning of the network of pathways involved in skeletogenesis and growth-plate development. Alterations of different genes of this network may result in overlapping phenotypes, as exemplified by disorders due to the impairment of the parathyroid hormone/parathyroid hormone-related protein pathway, and obtaining a correct diagnosis is sometimes challenging without a genetic confirmation. Five patients with Albright's hereditary osteodystrophy (AHO)-like skeletal malformations without a clear clinical diagnosis were analyzed by whole-exome sequencing (WES) and novel potentially pathogenic variants in parathyroid hormone like hormone (PTHLH) (BDE with short stature [BDE2]) and TRPS1 (tricho-rhino-phalangeal syndrome [TRPS]) were discovered. The pathogenic impact of these variants was confirmed by in vitro functional studies. This study expands the spectrum of genetic defects associated with BDE2 and TRPS and demonstrates the pathogenicity of TRPS1 missense variants located outside both the nuclear localization signal and the GATA ((A/T)GATA(A/G)-binding zinc-containing domain) and Ikaros-like binding domains. Unfortunately, we could not find distinctive phenotypic features that might have led to an earlier clinical diagnosis, further highlighting the high degree of overlap among skeletal syndromes associated with brachydactyly and AHO-like features, and the need for a close interdisciplinary workout in these rare patients. © 2021 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR).

Topics: Brachydactyly; DNA-Binding Proteins; Fingers; Hair Diseases; Humans; Langer-Giedion Syndrome; Nose; Parathyroid Hormone; Parathyroid Hormone-Related Protein; Pseudohypoparathyroidism; Repressor Proteins

When a sarcomatous neoplasm is identified in the breast, distinguishing metaplastic carcinoma, malignant phyllodes tumor (MPT), and primary sarcoma is a diagnostic challenge, especially on small biopsies, as all these tumors may have overlapping morphological features, thoroughly grossing with histological examination and immunohistochemical staining being the standard approach to aid in classifying these lesions. Recently, we identified a highly sensitive and specific breast carcinoma marker TRPS1 with high expression in metaplastic breast carcinoma. In the current study, we tested TRPS1 in MPTs and primary sarcoma of the breast. We found TRPS1 was highly expressed (95%) within spindle cell, chondro-osseous, and/or liposarcomatous components of MPTs, in all breast primary chondrosarcomas and extraskeletal osteosarcomas, but not in other sarcomas of the breast. In extramammary sarcomas, TRPS1 was expressed in 28% of conventional chondrosarcomas and 56% of osteosarcomas of bone, but rarely in undifferentiated pleomorphic sarcomas (UPSs), liposarcomas, and angiosarcomas. In summary, MPTs may share similar genetic background with metaplastic carcinoma exhibiting TRPS1 expression, and TRPS1 may play a role in chondro-osseous differentiation because of its expression in chondro-osseous sarcomas from both breast and extramammary sites. Our findings suggest TRPS1 may be clinically useful in distinguishing MPT and metaplastic carcinoma from primary breast sarcoma except for tumors with chondro-osseous differentiation.

Topics: Bone Neoplasms; Breast Neoplasms; Carcinoma; Chondrosarcoma; Female; Fingers; Hair Diseases; Humans; Langer-Giedion Syndrome; Nose; Osteosarcoma; Phyllodes Tumor; Repressor Proteins; Sarcoma; Soft Tissue Neoplasms

Trichorhinophalangeal syndrome (TRPS) is an extremely rare autosomal dominant multisystem disorder characterized by craniofacial and skeletal abnormalities. Three subtypes of TRPS have been described: TRPS type I, TRPS type II, and TRPS type III. Mutations in the TRPS1 gene can cause both TRPS type I and TRPS type III. Therefore, the genotype-phenotype correlation is crucial to determine the subtype. The current family study from Cyprus involves affected patients from 4 generations who presented with alopecia, unoperated umbilical hernia, caput quadratum, long philtrum, depressed nasal bridge, frontal bossing, pes planus, beaked nose, and some deformities in hands and feet. Sequence analysis of the TRPS1 gene revealed a novel c.2854_2858del (p.Asn952ArgfsTer2) frameshift variant leading to a premature stop codon. To the best of our knowledge, we report here the first case of a Turkish Cypriot family of 4 generations with a novel frameshift mutation leading to truncated protein in the TRPS1 gene causing TRPS type I clinical phenotype. Overall, as the genotype and phenotype correlation in TRPSI is still uncertain and complex, the present outcome can enhance our knowledge of this complicated, rare, and severe genetic disorder.

Topics: Codon, Nonsense; DNA-Binding Proteins; Fingers; Frameshift Mutation; Hair Diseases; Langer-Giedion Syndrome; Nose; Repressor Proteins; Transcription Factors

Topics: Facies; Female; Fingers; Foot Deformities, Congenital; Hair Diseases; Hand Deformities, Congenital; Humans; Mutation, Missense; Nose; Pedigree; Repressor Proteins; Toes; Young Adult

A 44-year-old woman with known trichorhinophalangeal syndrome presented with an unheralded out of hospital cardiac arrest. Transthoracic echocardiography showed severe left ventricular systolic dysfunction with an ejection fraction <25% and cardiac MRI confirmed a diagnosis of congenital non-ischaemic dilated cardiomyopathy. The case highlights a very rare syndrome, it is previously unknown association with dilated cardiomyopathy and the possible benefit of cardiac screening for patients with known trichorhinophalangeal syndrome.

Topics: Adult; Cardiomyopathy, Dilated; Echocardiography; Female; Fingers; Hair Diseases; Humans; Langer-Giedion Syndrome; Mass Screening; Nose; Out-of-Hospital Cardiac Arrest; Rare Diseases; Risk Factors

Okur-Chung neurodevelopmental syndrome (OCNDS) and tricho-rhino-phalangeal syndrome type I (TRPSI) are rare Mendelian diseases. OCNDS is caused by CSNK2A1 gene variants and TRPSI is caused by the TRPS1gene. However, to have two Mendelian diseases in one patient is even rarer.. A 6-year-10-month-old boy characterized by special facial features, short stature and mental retardation was referred to our pediatric endocrinology department. Whole-exome sequencing (WES) was done to detect the molecular basis of his disease. This patient was confirmed to carry two variants in the CSNK2A1 gene and one in the TRPS1 gene. The variant in the CSNK2A1 gene was vertically transmitted from his father, and the variant in TRPS1 gene from his mother. These two variants are classified as pathogenic and the causes of the presentation in this child. This patient's father and mother have subsequently been diagnosed as having OCNDS and TRPSI respectively.. This is the first reported case of a dual molecular diagnosis of tricho-rhino-phalangeal syndrome type I and Okur-Chung neurodevelopmental syndrome in the same patient. This patient is the first published example of vertical transmission of this recurrent CSN2A1 variant from parent to child. A novel variant in the TRPS1 gene that is pathogenic was also identified. In conclusion, identification of the variants in this patient expands the phenotypes and molecular basis of dual Mendelian diseases.

Topics: Asian People; Base Sequence; Child; Female; Fingers; Hair Diseases; Humans; Langer-Giedion Syndrome; Male; Neurodevelopmental Disorders; Nose; Pedigree

To explore the genetic etiology of a pedigree affected with tricho-rhino-phalangeal syndrome.. Next-generation sequencing (NGS) using a gene panel for hereditary osteopathies was carried out for the proband. Suspected mutation was validated in the proband and her parents by Sanger sequencing.. A heterozygous frameshift variation c.1995dupA (p.Gly666Argfs*20) of the TRPS1 gene was detected in the proband but not in her parents.. The novel c.1995dupA (p.Gly666Argfs*20) mutation of the TRPS1 gene probably underlies the disease in the proband.

Topics: DNA-Binding Proteins; Female; Fingers; Frameshift Mutation; Hair Diseases; Humans; Langer-Giedion Syndrome; Nose; Pedigree; Repressor Proteins; Transcription Factors

Trichorhinophalangeal syndrome type I (TRPSI) is a rare disorder that causes distinctive ectodermal, facial, and skeletal features affecting the hair (tricho-), nose (rhino-), and fingers and toes (phalangeal) and is inherited in an autosomal dominant pattern. TRPSI is caused by loss of function variants in

Topics: Aged; Child; DNA-Binding Proteins; Exons; Family; Female; Fingers; Gene Duplication; Hair Diseases; Humans; Langer-Giedion Syndrome; Male; Middle Aged; Mutation; Mutation, Missense; Nose; Pedigree; Phenotype; Repressor Proteins; RNA Splicing; Sequence Deletion; Transcription Factors; Zinc Fingers

Mutations of the TRPS1 gene cause trichorhinophalangeal syndrome (TRPS), a skeletal dysplasia with dental abnormalities. TRPS dental phenotypes suggest that TRPS1 regulates multiple aspects of odontogenesis, including the tooth number and size. Previous studies delineating Trps1 expression throughout embryonic tooth development in mice detected strong Trps1 expression in dental mesenchyme, preodontoblasts, and dental follicles, suggesting that TRPS dental phenotypes result from abnormalities in early developmental processes. In this study, Trps1

Topics: Alleles; Animals; Cell Differentiation; Cell Proliferation; Dental Caries; Epithelial Cells; Female; Fingers; GATA Transcription Factors; Gene Expression Regulation; Hair Diseases; Langer-Giedion Syndrome; Male; Mice; Mice, Inbred C57BL; Mice, Knockout; Molar; Nose; Odontogenesis; Repressor Proteins; Tooth Calcification; X-Ray Microtomography

Trichorhinophalangeal syndrome (TRPS) is rare genetic disorder with autosomal dominant inheritance. The TRPS1 gene is located on the long arm of the eighth chromosome (8q24.12). The phenotype is variable and presents a wide clinical spectrum. Most cases are characterised by thin, sparse scalp hair, distinctive facial dysmorphism, and various skeletal abnormalities, especially of the hands and feet. Characteristic facial features may include a "pear-shaped" nose, micrognathia, dental anomalies, prominent ears, elongated philtrum, and thin upper vermillion border. In most cases, affected individuals exhibit skeletal abnormalities including brachydactyly and clinodac-tyly, short metacarpals phalanges, short feet and metatarsals, and pectus carinatum and hip joint malformations. Additionally, patients may exhibit short stature. This report presents four cases of TRPS (three sporadic and one familial). Clinical presentation included typical facial features and vari-ous skeletal abnormalities. Some TRPS symptoms may mimic growth hormone deficiency and other endocrine disturbances. The aim of this article is to deliver TRPS symptomatology. The treatment of TRPS is symptomatic and supportive and requires the coordination of several specialists, including paediatricians, endocrinologists, orthopaedic surgeons, dermatologists, and medical rehabilitation and den-tal specialists. In some cases, recombinant growth hormone therapy may be necessary. Genetic counselling may be of benefit for affect-ed individuals and their families.. Zespół włosowo-nosowo-paliczkowy jest rzadką chorobą uwarunkowaną genetycznie, w większości przypadków o autosomalnie do-minującym sposobie dziedziczenia. Gen TRPS1 jest zlokalizowany na długim ramieniu chromosomu 8 – 8q24(8q24.12). Fenotyp jest zróżnicowany i prezentuje szerokie spektrum objawów klinicznych. Do charakterystycznych cech fenotypowych zalicza się rzadkie włosy, dysmorfię twarzoczaszki oraz zaburzenia kostno-szkieletowe, zwłaszcza w obrębie dłoni i stóp. Do typowych cech dysmorficz-nych twarzy należą: "gruszkowaty nos", mikrognacja, anomalie zębowe, wydatne uszy, wydłużona rynienka nosowa i wąska czerwień wargowa. W większości przypadków występują anomalie szkieletowe, takie jak klino- i brachydaktylia, skrócenie paliczków śródręcza i śródstopia, kurza klatka piersiowa oraz malformacje stawu biodrowego. Część pacjentów ma niedobór wzrostu. Artykuł przygotowano na podstawie serii czterech przypadków klinicznych (trzy sporadyczne i jeden rodzinny). Wszystkie dzieci pre-zentowały typowe dla TRPS cechy dysmorfii twarzoczaszki oraz różne anomalie układu kostno-szkieletowego. Przyczyną skierowania na Oddział Endokrynologii Dziecięcej było podejrzenie różnych endokrynopatii, w tym niedobór hormonu wzrostu, zaburzeń gospo-darki wapniowo-fosforanowej czy zespołu Turnera. Celem pracy jest przybliżenie symptomatologii TRPS. Leczenie jest objawowe i wymaga skoordynowanej współpracy wielu specjalistów, w tym lekarza pediatry, endokrynologa, ortopedy, dermatologa, specjalisty rehabilitacji medycznej czy chirurga szczękowego. Część pacjentów z niskorosłością i niedoborem GH może wymagać terapii substytu-cyjnej rGH. Doradztwo genetyczne może przynieść korzyści dotkniętym TRPS osobom i ich rodzinom.

Topics: Adolescent; Child; Child, Preschool; Female; Fingers; Hair Diseases; Humans; Langer-Giedion Syndrome; Male; Mutation; Nose; Phenotype; Poland; Repressor Proteins

Topics: Brachydactyly; DNA-Binding Proteins; Facies; Female; Fingers; Foot Deformities, Congenital; Frameshift Mutation; Genetic Markers; Growth Differentiation Factor 5; Hair Diseases; Hand Deformities, Congenital; Heterozygote; Humans; Male; Mutation, Missense; Nose; Pedigree; Repressor Proteins; Toes; Transcription Factors

Topics: Base Sequence; Child; DNA-Binding Proteins; Female; Fingers; Hair Diseases; Humans; Japan; Langer-Giedion Syndrome; Nose; Repressor Proteins; Sequence Deletion; Transcription Factors

Topics: Adolescent; Chromosome Deletion; Chromosomes, Human, X; Codon, Nonsense; DNA-Binding Proteins; Female; Fingers; Hair Diseases; Humans; Incidental Findings; Langer-Giedion Syndrome; Nose; Repressor Proteins; Transcription Factors

Tricho-rhino-phalangeal syndrome (TRPS) is a rare autosomal dominant genetic disorder characterized by distinctive craniofacial and skeletal abnormalities, while non-ossifying fibroma (NOF) is a common benign bone tumour in children and adolescents. To date, no case of TRPS coexisting with NOF has been reported. This report presents a 12-year-old girl who had the characteristic features of tricho-rhino-phalangeal syndrome and non-ossifying fibroma with a fibula fracture.. A 12-year-old girl was admitted to the Department of Endocrinology and Diabetes for evaluation of brachydactyly and a right fibula fracture. Clinical examination revealed sparse scalp hair, a characteristic bulbous pear-shaped nose, and brachydactyly with significant shortening of the fourth metatarsal. Neither intellectual disability nor multiple exostoses were observed. Radiography of both hands showed brachydactyly and cone-shaped epiphyses of the middle phalanges of the digits of both hands with deviation of the phalangeal axis. Genetic analysis of TRPS1 identified a heterozygous germline sequence variant (p.Ala932Thr) in exon 6 in the girl and her father. Approximately 1 month before being admitted to our department, the girl experienced a minor fall and suffered a fracture of the proximal fibula in the right lower limb. The pathological cytological diagnosis of the osteolytic lesion was NOF. Ten months following the surgery, the lesion on the proximal fibula of the girl disappeared.. In conclusion, the present study is the first to report a rare case of NOF with a pathologic fracture in the fibula of a girl with TRPS. The identification of a missense mutation, (p.Ala932Thr), in exon 6 of TRPS1 in this kindred further suggested that the patient had type I TRPS and indicated that mutations in this exon may be correlated with more pronounced features of the syndrome. Radiological techniques and genetic analysis played key roles in the definitive diagnosis.

Topics: Adult; Base Sequence; Bone Neoplasms; Brachydactyly; Child; DNA-Binding Proteins; Exons; Female; Fibroma; Fibula; Fingers; Fractures, Spontaneous; Gene Expression; Hair Diseases; Humans; Langer-Giedion Syndrome; Male; Mutation; Neoplasms; Nose; Paternal Inheritance; Radiography; Repressor Proteins; Transcription Factors

Topics: Fingers; Hair Diseases; Humans; Langer-Giedion Syndrome; Nose

Tricho-rhino-phalangeal syndrome (TRPS) is an autosomal dominant disorder characterized by craniofacial and skeletal malformations including short stature, thin scalp hair, sparse lateral eyebrows, pear-shaped nose and cone shaped epiphyses. This condition is caused by haploinsufficiency of the TRPS1 gene. Previous genotype-phenotype studies have correlated exon 6 missense mutations with TRPS type III, a severe form of type I with pronounced, facial characteristics, short stature and brachydactyly and differing from type II by the absence of exostoses and mental retardation.. We report the first case of a Moroccan family, a father and his three children, in which the diagnosis of type III TRPS was suspected based on severe clinical and radiological features. Molecular analysis of the TRPS1 gene revealed a novel missense mutation in exon 6, (p.Ala932Ser), located in the GATA-type DNA-binding zinc finger domain.. Our observations in this kindred support the previous genotype-phenotype results suggesting that patients with more pronounced facial characteristics and more severe shortening of hands and feet are more likely to have mutation in exon 6 of TRPS1.

Topics: Adolescent; Adult; DNA-Binding Proteins; Female; Fingers; Hair Diseases; Humans; Langer-Giedion Syndrome; Male; Morocco; Nose; Pedigree; Repressor Proteins; Transcription Factors; Young Adult

In 1987 Fitzsimmons and Guilbert described identical male twins with progressive spastic paraplegia, brachydactyly with cone shaped epiphyses, short stature, dysarthria, and "low-normal" intelligence. In subsequent years, four other patients, including one set of female identical twins, a single female child, and a single male individual were described with the same features, and the eponym Fitzsimmons syndrome was adopted (OMIM #270710). We performed exome analysis of the patient described in 2009, and one of the original twins from 1987, the only patients available from the literature. No single genetic etiology exists that explains Fitzsimmons syndrome; however, multiple different genetic causes were identified. Specifically, the twins described by Fitzsimmons had heterozygous mutations in the SACS gene, the gene responsible for autosomal recessive spastic ataxia of Charlevoix Saguenay (ARSACS), as well as a heterozygous mutation in the TRPS1, the gene responsible in Trichorhinophalangeal syndrome type 1 (TRPS1 type 1) which includes brachydactyly as a feature. A TBL1XR1 mutation was identified in the patient described in 2009 as contributing to his cognitive impairment and autistic features with no genetic cause identified for his spasticity or brachydactyly. The findings show that these individuals have multiple different etiologies giving rise to a similar phenotype, and that "Fitzsimmons syndrome" is in fact not one single syndrome. Over time, we anticipate that continued careful phenotyping with concomitant genome-wide analysis will continue to identify the causes of many rare syndromes, but it will also highlight that previously delineated clinical entities are, in fact, not syndromes at all. © 2016 Wiley Periodicals, Inc.

Topics: Brachydactyly; Child; DNA-Binding Proteins; Dysarthria; Exome; Female; Fingers; Hair Diseases; Heat-Shock Proteins; High-Throughput Nucleotide Sequencing; Humans; Langer-Giedion Syndrome; Male; Muscle Spasticity; Nose; Nuclear Proteins; Receptors, Cytoplasmic and Nuclear; Repressor Proteins; Spastic Paraplegia, Hereditary; Spinocerebellar Ataxias; Transcription Factors

The trichorhinophalangeal syndrome is a rare genetic syndrome with characteristic craniofacial and skeletal abnormalities including hip pathology in variable manifestation. We describe hip involvement with Perthes-like changes and a novel mutation of the TRPSI gene in a family with 4 affected individuals. This case series underlines the clinical significance of rare genetic disorders such as TRPS that among other differential diagnoses should be kept in mind when children present with Perthes-like changes of the hip joint.

Topics: Abnormalities, Multiple; Child, Preschool; Diagnosis, Differential; DNA-Binding Proteins; Fingers; Genetic Testing; Hair Diseases; Hip Joint; Humans; Langer-Giedion Syndrome; Legg-Calve-Perthes Disease; Male; Mutation; Nose; Osteonecrosis; Pedigree; Radiography; Repressor Proteins; Transcription Factors

A representative phenotype of patients with tricho-rhino-phalangeal syndrome (TRPS) is sparse hair. To understand the developmental defects of these patient's hair follicles, we analyzed the development of hair follicles histologically and biochemically using Trps1 deficient (KO) mice. First, we compared the numbers of primary hair follicles in wild-type (WT) and KO embryos at different developmental stages. No differences were observed in the E14.5 skins of WT and KO mice. However, at later time points, KO fetal skin failed to properly develop secondary hair follicles, and the number of secondary hair follicles present in E18.5 KO skin was approximately half compared to that of WT skin. Sonic hedgehog expression was significantly decreased in E17.5 KO skin, whereas no changes were observed in Eda/Edar expression in E14.5 or E17.5 skins. In addition, Noggin expression was significantly decreased in E14.5 and E17.5 KO skin compared to WT skin. In parallel with the suppression of Noggin expression, BMP signaling was promoted in the epidermal cells of KO skins compared to WT skins as determined by immunohistochemistry for phosphorylated Smad1/5/8. The reduced number of secondary hair follicles was restored in skin graft cultures treated with a Noggin and BMP inhibitor. Furthermore, decreased cell proliferation, and increased apoptosis in KO skin was rescued by Noggin treatment. Taken together, we conclude that hair follicle development in Trps1 KO embryos is impaired directly or indirectly by decreased Noggin expression.

Topics: Animals; Apoptosis; Carrier Proteins; Cell Proliferation; Female; Fingers; GATA Transcription Factors; Hair Diseases; Hair Follicle; Humans; Langer-Giedion Syndrome; Mice; Mice, Knockout; Morphogenesis; Nose; Repressor Proteins

Trichorhinophalangeal syndrome type 1 is a rare skeletal dysplasia of autosomal-dominant inheritance due to defects in the TRPS-1 gene. The syndrome is characterised by sparse slow-growing hair, a bulbous pear-shaped nose, cone-shaped epiphyses and deformities of the interphalangeal joints resembling those in rheumatoid arthritis. We present a case of trichorhinophalangeal syndrome in a 23-year-old man who presented with symmetrical painless progressive deformity of the fingers in both hands.

Topics: Arthritis, Rheumatoid; Diagnosis, Differential; Disease Progression; Fingers; Hair Diseases; Humans; Langer-Giedion Syndrome; Male; Nose; Occupational Therapy; Radiography; Toes; Young Adult

Type 1 Trichorhinophalangeal syndrome (TRPS) is characterized by typical facial and skeletal abnormalities. These patients frequently exhibit short stature; however, only one case with growth hormone (GH) deficiency can be found in the literature. Our patient is a 10-year-old girl with two novel nonsense pathogenic mutations in the TRPS1 gene, both in heterozygosity: c. 1198C>T (p. Gln400X) and c.2086C>T (p. Arg696X). She has an additional GH deficiency. The patient is short in stature, with a growth velocity of 1.5 cm per year (SDS - 4.07), a bone age of 4.5 years, and she shows no response to the GH stimulation tests. According to a previous report of an identical case, catch-up growth will occur after beginning GH treatment. We believe that GH stimulation tests should be performed on patients with TRPS1 exhibiting a growth velocity below the normal range expected for their age and sex. If the result is subnormal, then GH therapy should be attempted.

Topics: Body Height; Child; Codon, Nonsense; DNA-Binding Proteins; Female; Fingers; Growth Hormone; Hair Diseases; Humans; Langer-Giedion Syndrome; Nose; Recombinant Proteins; Repressor Proteins; Transcription Factors

Trichorhinophalangeal syndrome type I (TRPSI) is a genetic disorder characterized by sparse hair, a bulbous nasal tip, short stature with severe generalized shortening of all phalanges, metacarpal and metatarsal bones and cone-shaped epiphyses. This syndrome is caused by autosomal dominant mutations in the TRPS1 gene. However, because recurrence has been observed in siblings from healthy parents, an autosomal recessive mode of inheritance has also been suggested. We report on a male patient, born to healthy unrelated parents, with TRPSI. Using Sanger sequencing, we identified a mutation in the TRPS1 gene (c.2735 G>A, P.Cys912Tyr). The same mutation was detected as a 10% mosaic mutation by Pyrosequencing in blood-derived DNA from his healthy mother. To our knowledge, this is the first time that somatic mosaicism has been identified in TRPSI. This data combined with the observations of recurrences in siblings from healthy parents modifies the genetic counseling for TRPSI, which should discuss a 5-10 percent recurrence risk for healthy parents with an affected child because of the possibility of germinal mosaicism.

Topics: Abnormalities, Multiple; Child; DNA-Binding Proteins; Fingers; Genetic Counseling; Hair Diseases; Humans; Langer-Giedion Syndrome; Male; Mosaicism; Nose; Repressor Proteins; Transcription Factors

Topics: Child; Codon, Nonsense; DNA-Binding Proteins; Female; Fingers; Hair Diseases; Humans; Japan; Langer-Giedion Syndrome; Nose; Repressor Proteins; Transcription Factors

Trichorhinophalangeal syndrome (TRPS) is a rare, autosomal dominant malformation syndrome characterized by hair, craniofacial and skeletal abnormalities, skin laxity, deformation of phalanges and anomalies of pelvis, femurs, and tibias. Three subtypes have been described: TRPS I, caused by mutations in TRPS1 gene on chromosome 8; TRPS II, a microdeletion syndrome affecting the TRPS1 and EXT1 genes; and TRPS III, a form with severe brachydactyly, due to short metacarpals, and severe short stature, but without exostoses. We present the case of a 7-year-old boy, affected by TRPS with a severe osteoporosis and several spontaneous bone fractures, an association described only once in the literature, successfully treated with biphosphonates. Bone mineral density (BMD) at dual-energy X-ray Absorptiometry (DXA) was of 0.331 g/cm(2) at lumbar spine with. He had four spontaneous femoral fractures in a year, and for this reason he was been operated for positioning intramedullary osteosynthesis and orthopedic supports. Due to the severity of the clinical and radiological pattern it was established, after approval of the Ethical Committee, to begin off-label therapy with infusions of neridronate at a dose of 2 mg/kg IV every 3 months. The treatment was, in this patient, effective both in terms of clinical (absence of new fractures) and mineralomethric (+45% BMD ath the lumbar level). We therefore suggest that treatment with biphosponates can be taken in account as a possible therapeutic option in case of bone fragility in patients with TRPSI.

Topics: Bone and Bones; Bone Density; Bone Density Conservation Agents; Child; Clodronic Acid; DNA Mutational Analysis; DNA-Binding Proteins; Fingers; Hair Diseases; Humans; Langer-Giedion Syndrome; Male; Nose; Osteoporosis; Phenotype; Radiography; Repressor Proteins; Transcription Factors

The tricho-rhino-phalangeal syndrome type III (TRPS III) is a rare autosomal dominantly inherited condition. The main clinical features are sparse and slow-growing hair and nails, a pear-shaped nose with a bulbous tip, elongated and flat philtrum, thin upper lip, cone-shaped epiphyses of the phalanges, and short stature. All patients have a point mutation in the TRPS1 gene.. In this paper, we present a 13-year-old female with the typical clinical features of TRPS III, extreme growth retardation, severe deformities of both proximal radii resulting in limited extension of the elbows, and chronic renal failure (CRF) in addition. Molecular diagnostics revealed a missense mutation in exon 6 of TRPS1 that she inherited from her father who is also affected with TRPS III, but does not have CRF. In the index patient, the CRF was found to be due to bilateral renal hypodysplasia (RHD).. Beside the renal dysplasia, the girl had severe deformities of the proximal radii - findings which have not been reported so far in TRPS III.

Topics: Abnormalities, Multiple; Adolescent; DNA-Binding Proteins; Female; Fingers; Growth Disorders; Hair Diseases; Humans; Kidney; Kidney Failure, Chronic; Langer-Giedion Syndrome; Nose; Point Mutation; Radius; Repressor Proteins; Syndrome; Transcription Factors

Trichorhinophalangeal syndrome type I [OMIM #190350] is an autosomal dominant disorder. Common features are: Slowly growing sparse hair, laterally thin eyebrows, bulbous tip of the nose, long philtrum, thin upper lip, protruding ears. Common skeletal anomalies include shortening of phalanges and metacarpals causing mild to severe brachydactyly, cone shaped epiphyses, hip dysplasia and short stature. Recently many reports have been published on the use of assisted reproductive technology (ART) and the increased risk of congenital major malformations or syndromes. We present a 6 years old Turkish Trichorhinophalangeal syndrome (TRPS) case of a twin pair after in vitro fertilization (IVF). TRPS with IVF pregnancy has not been reported previously. This new case reported herein will contribute to a better understanding whether ART pregnancy increases congenital malformations.

Topics: Abnormalities, Multiple; Child; Female; Fertilization in Vitro; Fingers; Hair Diseases; Humans; Langer-Giedion Syndrome; Language Development Disorders; Nose; Turkey; Twins

Trichorhinophalangeal syndrome (TRPS) is a rare autosomal dominant genetic disorder characterised by distinctive craniofacial and skeletal abnormalities. TRPS is generally associated with mutations in the TRPS1 gene at 8q23.3 or microdeletions of the 8q23.3-q24.11 region. However, three deletions affecting the same chromosome region and a familial translocation t(8;13) co-segregating with TRPS, which do not encompass or disrupt the TRPS1 gene, have been reported. A deregulated expression of TRPS1 has been hypothesised as cause of the TRPS phenotype of these patients.. We report the clinical and molecular characterisation of a 57-year-old Caucasian woman carrying the t(2;8)(p16.1;q23.3) de novo balanced translocation. The proband presented with peculiar clinical features (severe craniofacial dysmorphism, alopecia universalis, severe scoliosis, mitral valve prolapse, mild mental impairment and normal growth parameters) that partially overlap with TRPS I. Mutational and array CGH analyses ruled out any genetic defect affecting TRPS1 or genomic alteration at the translocation breakpoint or elsewhere in the genome. Breakpoint mapping excluded disruption of TRPS1, and revealed that the chromosome 8q23.3 breakpoint was located within the IVS10 of the long intergenic non-coding RNA LINC00536, at approximately 300 kb from the TRPS1 5' end. Conversely, the 2p16.1 breakpoint mapped within a LINE sequence, in a region that lacks transcriptional regulatory elements. As a result of the translocation, nucleotide base pair additions and deletions were detected at both breakpoint junction fragments, and an evolutionarily conserved VISTA enhancer element from 2p16.1 was relocated at approximately 325 kb from the TRPS1 promoter.. We suggest that the disruption of the genomic architecture of cis regulatory elements downstream the TRPS1 5' region, combined with the translocation of a novel enhancer element nearby TRPS1, might be the pathogenetic mechanism underpinning the proband's phenotype. The clinical and genetic characterisation of the present subject allowed us to make a genetic diagnosis in the context of a known syndrome, contributing to a better comprehension of the complex transcriptional regulation of TRPS1 and TRPS ethiopathogenesis.

Topics: Base Sequence; Chromosome Breakpoints; Chromosome Mapping; Chromosomes, Human, Pair 2; Chromosomes, Human, Pair 8; Comparative Genomic Hybridization; Computational Biology; DNA Mutational Analysis; DNA-Binding Proteins; Female; Fingers; Hair Diseases; Hand Deformities; Humans; In Situ Hybridization, Fluorescence; Langer-Giedion Syndrome; Middle Aged; Mutation; Nose; Phenotype; Radiography; Repressor Proteins; Transcription Factors; Translocation, Genetic

Tricho-rhino-phalangeal syndrome (TRPS) is an autosomal-dominant disease characterized by sparse and slow-growing scalp hair and craniofacial and skeletal abnormalities. We report here the case of two girls and their father who had TRPS type 1 and received a diagnosis of a new mutation of TRPS1 based on their clinical symptoms. Moreover, histological studies on skin samples obtained from one of the patients showed enhanced signal transducers and activator of transcription (STAT) 3 expression in the outer root sheath. However, TRPS1 protein expression was not reduced in the patient's follicles. These findings indicate that truncated TRPS1 protein from the mutant allele may be stably expressed in the patient's follicles and that enhanced STAT3 expression may be involved in the development of sparse and thin scalp hair in TRPS.

Topics: Adult; Child, Preschool; DNA Mutational Analysis; DNA-Binding Proteins; Female; Fingers; Hair; Hair Diseases; Humans; Langer-Giedion Syndrome; Male; Nose; Repressor Proteins; Sequence Deletion; Transcription Factors

Topics: Abnormalities, Multiple; Analgesics; Arthralgia; Epiphyses; Fingers; Hair Diseases; Humans; Langer-Giedion Syndrome; Male; Nose; Physical Therapy Modalities; Radiography; Rare Diseases; Young Adult

Trichorhinophalangeal syndrome (TRPS) is an autosomal-dominant congenital hair loss disease characterized by sparse and slow-growing scalp hair, craniofacial and skeletal abnormalities, pear-shaped nose, thin upper lip, brittle and thin toenails, and bilateral brachydactyly of the big toes. We report a case of TRPS1 exhibiting these clinical features with a novel heterozygous single nucleotide substitution in exon 3 of the TRPS1 gene. By immunohistochemical analysis of a biopsied specimen of the patient's alopecia lesion, we found for the first time that the expression level of TRPS1 was markedly reduced in the epidermis and the outer root sheath of hair follicles as compared to a normal subject. In addition, higher expression of phospho-Stat3 was found consequent to the loss of TRPS1 in the outer root sheath.

Topics: Child, Preschool; Codon, Nonsense; DNA-Binding Proteins; Epithelial Cells; Female; Fingers; Hair Diseases; Hair Follicle; Humans; Langer-Giedion Syndrome; Nasal Mucosa; Nose; Repressor Proteins; Transcription Factors

Tricho-rhino-phalangeal syndrome (TRPS) is a rare autosomal dominant disorder. Deletion or mutation of the TRPS1 gene leads to the tricho-rhino-phalangeal syndromes type I or type III. In this article, we describe a Chinese patient affected with type I TRPS and showing prominent pilar, rhinal and phalangeal abnormalities. Mutational screening and sequence analysis of TRPS1 gene revealed a previously unidentified four-base-pair deletion of nucleotides 1783-1786 (c.1783_1786delACTT). The mutation causes a frame shift after codon 593, introducing a premature stop codon after 637 residues in the gene sequence. This deletion is an unquestionable loss-of-function mutation, deleting all the functionally important parts of the protein. Our novel discovery indicates that sparse hair and metacarpal defects of tricho-rhino-phalangeal syndromes in this patient are due to this TRPS1 mutation. And this data further supports the critical role of TRPS1 gene in hair and partial skeleton morphogenesis.

Topics: Amino Acid Sequence; Asian People; DNA Mutational Analysis; DNA-Binding Proteins; Exons; Fingers; Frameshift Mutation; Hair Diseases; Haploinsufficiency; Humans; Langer-Giedion Syndrome; Male; Nose; Repressor Proteins; Sequence Deletion; Transcription Factors; Young Adult; Zinc Fingers

Trichorhinophalangeal syndrome type I is a rare autosomal dominant disorder characterized by cone-shaped epiphysis, sparse fine hair, pear-shaped nose and variable growth retardation. The typical craniofacial features include thin upper lip, elongated philtrum, large outstanding ears, shortened posterior facial height associated with short mandibular ramus and reduced and superiorly deflected posterior cranial base. This report describes a 17-year-old male patient with trichorhinophalangeal syndrome type I and a detailed description of the craniofacial radiographic findings, including the use of cone beam computed tomography images for determination of the airway and temporomandibular joint discrepancies.

Topics: Adolescent; Airway Obstruction; Cephalometry; Cone-Beam Computed Tomography; Facial Bones; Fingers; Hair Diseases; Humans; Langer-Giedion Syndrome; Male; Nose; Temporomandibular Joint Disorders

Topics: Abnormalities, Multiple; Child; Craniofacial Abnormalities; Diagnosis, Differential; Female; Finger Phalanges; Fingers; Hair; Hair Diseases; Humans; Langer-Giedion Syndrome; Nails, Malformed; Nose

Trichorhinophalangeal syndrome type I (TRPS I) is a rare autosomal dominant syndrome caused by haploinsufficiency of TRPS1 due to point mutations or deletions. Here, we report the first familial TRPS I due to a t(8;13)(q23.3;q21.31) translocation breakpoint <100 kb from the 5' end of TRPS1. Based on the additional abnormalities observed exclusively in the index patient that are mainly compatible with clinical features of TRPS, her phenotype was defined as expanded TRPS I including brain malformations and intellectual disability. Initial analyses did not reveal any genetic defect affecting TRPS1 or any genomic alteration within the breakpoint regions or elsewhere in the genome. The pathogenic chromosome 8q23.3 breakpoint is at position g.116,768,309_116,768,310 within a transposon type I element, 87 kb from the TRPS1 5' end. The 13q21.31 breakpoint is within a tandem repeat region at position g.65,101,509_65,101,510 (genome assembly GRCh37/hg19). This breakpoint is flanked by protocadherin 9 (PCDH9) and protocadherin 20 (PCDH20). As an outcome of the translocation, an evolutionarily conserved non-coding VISTA enhancer element from 13q21.31 is placed within the TRPS1 5' region, 1,294 bp from the breakpoint. The increased expression of TRPS1 found by three independent methods is most probably translocation allele derived and driven by the translocated enhancer element. The index patient's expanded phenotype presumably involves the epithelial-to-mesenchymal transition pathway that may be due to TRPS1 overexpression. Together, these findings support that the reported translocation-associated phenotypes are "cis-ruption" and TRPS1 overexpression related, the latter most probably caused by the novel enhancer element in the TRPS1 5' region.

Topics: Alleles; Base Sequence; Cell Line; Comparative Genomic Hybridization; DNA-Binding Proteins; Female; Fingers; Gene Amplification; Gene Expression; Hair Diseases; Humans; In Situ Hybridization, Fluorescence; Langer-Giedion Syndrome; Male; Molecular Sequence Data; Nose; Pedigree; Phenotype; Repressor Proteins; RNA; Sequence Analysis, DNA; Transcription Factors; Translocation, Genetic

Topics: Adolescent; Asian People; DNA Mutational Analysis; DNA-Binding Proteins; Exons; Fingers; Hair Diseases; Humans; Langer-Giedion Syndrome; Male; Mutation; Nose; Repressor Proteins; Sequence Analysis, DNA; Transcription Factors

Topics: Adult; Amino Acid Sequence; Base Sequence; Child; Child, Preschool; Codon; DNA-Binding Proteins; Facies; Female; Fingers; Gene Order; Hair Diseases; Hand Deformities, Congenital; Humans; Intellectual Disability; Langer-Giedion Syndrome; Male; Molecular Sequence Data; Mutation; Nose; Radiography; Repressor Proteins; Transcription Factors

Topics: Child; Female; Fingers; Hair Diseases; Humans; Langer-Giedion Syndrome; Nose; Radiography

Autosomal dominant tricho-rhino-phalangeal syndrome I (TRPS I) is due to mutations in the TRPS1 gene. Tricho-rhino-phalangeal syndrome I is characterized by peculiar face and skeletal anomalies. Cone-shaped epiphyses are the characteristic radiographic findings.. To describe 2 families with TRPS I and 2 novel mutations in the TRPS1 gene.. The study included 2 nonrelated families with TRPS I. All exons of the TRPS1 gene were analyzed from genomic DNA.. The TRPS1 gene mutation analysis showed in family 1 the c.978C>A nonsense mutation within exon 4 and in family 2 the c.164A>C missense mutation within exon 3.. We found 2 families with TRPS1 caused by 2 novel mutations in the TRPS gene, particularly a missense mutation in exon 3, outside the GATA zinc finger domain, that leads a mild TRPS phenotype. Our data show a higher genotypic spectrum in the TRPS I and demonstrate that mutations in the amino terminus of the transcription factor result in TRPS I syndrome.

Topics: Adolescent; Adult; Codon, Nonsense; DNA-Binding Proteins; Female; Fingers; Hair Diseases; Humans; Langer-Giedion Syndrome; Mutation, Missense; Nose; Repressor Proteins; Transcription Factors

Tricho-rhino-phalangeal syndrome type I (TRPSI) is a rare autosomal dominant hereditary disorder characterized by sparse hair, bulbous nose, long philtrum, thin upper lip, and skeletal abnormalities including cone-shaped epiphyses, shortening of the phalanges, and short stature. TRPSI is caused by mutations in the TRPS1 gene. Herein, we report two Korean cases of TRPSI. Although both patients (a 17-year-old-female and a 14-year-old male) had typical clinical findings, Patient 1 had an additional growth hormone (GH) deficiency. Treatment with recombinant human growth hormone (rhGH) 0.7 IU/kg/week led to an increase in growth velocity. Over 10 years of GH therapy, the mean growth velocity was 5.7 ± 0.9 cm/year. However, the patient 2 did not show apparent GH deficiency by GH stimulation test, had a poor response with rhGH therapy and GH therapy was discontinued after 6 months. Upon genetic analysis of the TRPS1 gene, two mutations were found. Patient 1 had a heterozygous mutation c.2520dupT (p.Arg841LysfsX3) which had not been previously reported. Patient 2 had a known nonsense mutation c.1630C>T (p.Arg544X). In summary, we were the first to report Korean patients with mutation of TRPS1.

Topics: Adolescent; Amino Acid Sequence; Asian People; Base Sequence; Child; Child, Preschool; DNA Mutational Analysis; DNA-Binding Proteins; Female; Fingers; Hair Diseases; Hand; Human Growth Hormone; Humans; Infant, Newborn; Langer-Giedion Syndrome; Male; Molecular Sequence Data; Mutation; Nose; Radiography; Repressor Proteins; Republic of Korea; Transcription Factors

Mutations of the short stature homeobox-containing (SHOX) gene on the pseudoautosomal region of the sex chromosomes cause short stature. GH treatment has been recently proposed to improve height in short patients with SHOX deficiency. The aim of this study was to evaluate GH secretion and analyze growth and safety of recombinant human GH (rhGH) therapy in short children and adolescents with SHOX deficiency.. We studied 16 patients (10 females; 9.7 ± 2.9 years old; height -2.46 ± 0.82 standard deviation score, SDS) with SHOX deficiency. All subjects underwent auxological evaluations, biochemical investigations, and were treated with rhGH (0.273 ± 0.053 mg/kg/week).. Impaired GH secretion was present in 37.5% of the studied subjects. Comparing baseline data with those at the last visit, we found that rhGH treatment improved growth velocity SDS (from -1.03 ± 1.44 to 2.77 ± 1.95; p = 0.001), height SDS (from -2.41 ± 0.71 to -1.81 ± 0.87; p < 0.001), and IGF-1 values (from -0.57 ± 1.23 to 0.63 ± 1.63 SDS, p = 0.010) without affecting body mass index SDS. Height SDS measured at the last visit was significantly correlated with chronological age (r = -0.618, p = 0.032), bone age (r = -0.582, p = 0.047) and height SDS (r = 0.938, p < 0.001) at the beginning of treatment. No adverse events were reported on rhGH therapy which was never discontinued.. These data showed that impaired GH secretion is not uncommon in SHOX deficiency subjects, and that rhGH therapy may be effective in increasing height in most of these patients independent of their GH secretory status, without causing any adverse events of concern.

Topics: Adolescent; Body Height; Child; Child, Preschool; Female; Fingers; Growth Disorders; Growth Hormone; Hair Diseases; Homeodomain Proteins; Human Growth Hormone; Humans; Langer-Giedion Syndrome; Male; Nose; Osteochondrodysplasias; Recombinant Proteins; Short Stature Homeobox Protein

The authors report an unusual case of intrafollicular collagenous crystalloids in an 86-year-old woman. The presence of collagenous crystalloids within the follicular epithelium is intriguing and has not been described previously.

Topics: Aged, 80 and over; Carcinoma, Squamous Cell; Collagen; Crystallization; Crystalloid Solutions; Diagnosis, Differential; Female; Hair Diseases; Hair Follicle; Humans; Isotonic Solutions; Nose; Skin Neoplasms

Topics: Diagnosis, Differential; Female; Hair Diseases; Humans; Middle Aged; Nose; Nose Neoplasms; Rare Diseases

The trichorhinophalangeal syndrome (TRPS) is a hereditary, skeletal dysplasia which has a characteristic clinical presentation and is classified in types 1, 2 and 3, based on phenotype and genotype. Typical findings may be mild and many patients probably remain undiagnosed.. The paper is based on four case reports and provides a short review of the condition.. Our four patients all have typical facial features, such as a large nose and thin upper lip, thin hair and short curved fingers with characteristic radiological findings. The condition is autosomal dominant and caused by a mutation in the TRPS1 gene, which codes a gene-regulating protein involved in development of hair and modulation of chondrocytes. The diagnosis can be based on clinical findings, but DNA-analysis can be of help in unclear situations. Two of our patients were diagnosed from clinical and radiological findings, but for the two others genetic examinations were done as well. There is no causal treatment, but the diagnosis can give patients an explanation of their problems, and genetic counseling for the patient and family can be offered. Orthopedic surgery and cosmetic aids are valuable for many.. In an increasingly technified medical daily life, the clinical view is still the most important tool in diagnosing patients with this condition.

Topics: Abnormalities, Multiple; Adolescent; Child; Child, Preschool; Craniofacial Abnormalities; Female; Fingers; Genetic Counseling; Hair Diseases; Hand Deformities, Congenital; Humans; Hypotrichosis; Langer-Giedion Syndrome; Nose

Topics: Abnormalities, Multiple; Adolescent; Exons; Fingers; Hair Diseases; Humans; Male; Mutation, Missense; Nose; Syndrome

Topics: Bone Density; Child; DNA-Binding Proteins; Female; Fingers; Hair Diseases; Human Growth Hormone; Humans; Langer-Giedion Syndrome; Male; Nose; Repressor Proteins; Transcription Factors

Seventeen solitary nasal tumors that fulfilled all diagnostic criteria of so-called neurofollicular hamartoma, apart from distinct S100-positivity, were compared histopathologically and immunohistochemically with seven typical trichodiscomas from a similar clinical setting. Both the S100-negative neurofollicular hamartoma-like tumors and the trichodiscomas expressed an identical CD13-positive/CD34-positive fibrocytic immunophenotype without co-expression of neural/perineural (S100, neurofilament, epithelial membrane antigen), myogenic (desmin, calponin, muscle-specific actin, and alpha-smooth muscle actin), or melanocytic (S100, HMB45, NKI/C3, MelanA) epitopes. Histopathologically, there was striking morphologic overlap between trichodiscoma and S100-negative neurofollicular hamartoma-like tumor, apart from a highly characteristic fascicularly organized cellular fibrocytic stroma in the latter. We conclude that fibrofolliculoma/trichodiscoma and neurofollicular hamartoma-like tumor are morphologic variants of a single hamartomatous entity in which neurofollicular hamartoma-like tumor occupies the cellular pole of the morphologic spectrum. The entity formerly known as neurofollicular hamartoma appears to be nothing but a particularly cellular trichodiscoma with a distinctively organized stroma composed of CD34-positive fibrocytes. We therefore propose the new term spindle cell predominant trichodiscoma (SCPT) for this particular variant of the morphologic fibrofolliculoma/trichodiscoma spectrum.

Topics: Adult; Aged; Biomarkers; Female; Hair Diseases; Hair Follicle; Hamartoma; Humans; Immunohistochemistry; Male; Middle Aged; Nose; Skin

A 17-month-old girl with a partial trisomy of distal 8q derived from her mother, who has a mosaic 8q23.3----q24.13 deletion, was studied. Both showed a relatively mild phenotype of trichorhinophalangeal syndrome I. The karyotype of the proposita was designated as: 46,XX,-8,+der(8),inv ins(8;8)(p23.1;q24.13q23.3)mat. Her phenotype was considered similar to that of her mother despite the trisomies of distal 8q. She seems to be the first example of a partial trisomy of distal 8q derived from a parent with an interstitial deletion of a distal 8q segment and trichorhinophalangeal syndrome I.

Topics: Adult; Chromosome Deletion; Chromosomes, Human, Pair 8; Female; Fingers; Hair Diseases; Humans; Infant; Karyotyping; Mosaicism; Nose; Syndrome; Trisomy

A three generation family from northern Sweden with both trichorhinophalangeal syndrome type I (TRP I) and systemic lupus erythematosus (SLE)-like syndrome with complement C4 homozygous null alleles is described. Five family members in three generations were affected by the TRP I syndrome, indicating autosomal dominant inheritance. Two members had clinical and laboratory signs of SLE and two other members SLE-like syndrome. All living family members in the first and second generation had homozygous C4A null alleles. In three of the adults the two syndromes occurred simultaneously, probably in this family by coincidence.

Topics: Abnormalities, Multiple; Adolescent; Aged; Alleles; Anaphylatoxins; Complement C4a; Female; Fingers; Genes, Dominant; Hair Diseases; Homozygote; Humans; Lupus Erythematosus, Systemic; Male; Middle Aged; Nose; Pedigree; Syndrome

We report three cases of tricho-rhino-phalangeal syndrome (TRPS) type I in a Belgian family. They presented typical characteristics such as a pear-shaped nose, and short, deformed fingers with cone-shaped epiphyses of some middle phalanges of the hands. Hair growth was practically normal in our patients, except for some narrowing of the lateral part of the eyebrows. Perthes-like hip dysplasia was documented in two of our cases. The proband presented at the age of 31 with Kienböch's disease of the right wrist. Blood and urine analysis showed no clear anomalies. In this patient, echography revealed a renal cyst containing a stone. The relationship of these findings to TRPS is discussed.

Topics: Adult; Belgium; Epiphyses; Female; Hair Diseases; Humans; Legg-Calve-Perthes Disease; Nose; Osteoarthritis; Osteochondritis; Syndrome

A family exhibiting the classical features of the tricho-rhino-phalangeal syndrome is presented.

Topics: Adolescent; Epiphyses; Female; Fingers; Hair Diseases; Humans; Male; Nose; Pedigree; Syndrome

Topics: Adolescent; Adult; Diagnosis, Differential; Female; Fingers; Genes, Dominant; Growth Disorders; Hair Diseases; Humans; Metatarsus; Nose; Syndrome

Topics: Child; Congenital Abnormalities; Deafness; Eyebrows; Eyelids; Genetics, Medical; Hair; Hair Diseases; Humans; Iris; Myopia; Nose; Nose Deformities, Acquired; Pigmentation Disorders; Waardenburg Syndrome

Topics: Folliculitis; Hair Diseases; Humans; Lip; Nasopharynx; Nose; Staphylococcal Infections; Tinea

Topics: Folliculitis; Hair Diseases; Humans; Nose; Penicillins; Skin; Staphylococcus