phenylephrine-hydrochloride and Hand-Deformities

The Gorlin-Goltz syndrome is characterized by four primary symptoms: multiple nevoid basal cell epitheliomas that usually undergo malignant transformation; jaw keratocysts that show constant growth; skeletal anomalies; and intracranial calcifications. A myriad of additional findings may also be noted. Among the most frequent are: palmar and plantar pits, a characteristic flattened facies and broad nasal root, frontal and parietal bossing, mandibular prognathia, hypertelorism, strabismus, dystrophia of the canthi, and clefts of the lip, alveolus, and/or palate. In this study, we review the literature and our 25 cases of Gorlin-Goltz syndrome patients, questioning their incidence of cleft formations (8.5%) as compared to the general population (0.1%). It is our contention that all patients who present with an orofacial cleft warrant deeper investigation as to the presence of additional signs indicative of Gorlin-Goltz syndrome. The nevi turn malignant with time, and thus, early diagnosis, follow-up, and treatment are imperative.

Topics: Adult; Alveolar Process; Basal Cell Nevus Syndrome; Brain Diseases; Calcinosis; Cell Transformation, Neoplastic; Cleft Lip; Cleft Palate; Diagnosis, Differential; Eyelid Diseases; Face; Facies; Female; Follow-Up Studies; Foot Deformities; Frontal Bone; Hand Deformities; Humans; Hypertelorism; Incidence; Jaw Cysts; Male; Mouth Abnormalities; Nose; Parietal Bone; Prognathism; Strabismus

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

Topics: Congenital Abnormalities; Disorder of Sex Development, 46,XY; Disorders of Sex Development; Eye Manifestations; Face; Facial Expression; Female; Foot Diseases; Genetics, Medical; Hand Deformities; Humans; Hypospadias; Infant; Infant, Newborn; Intellectual Disability; Jaw; Male; Microcephaly; Movement Disorders; Nose; Nose Deformities, Acquired; Pyloric Stenosis; Retrognathia; Skin Manifestations; Strabismus

Topics: Alopecia; Child; Congenital Abnormalities; Fingers; Genetics, Medical; Hand Deformities; Humans; Infant; Nose; Nose Deformities, Acquired; Ophthalmology; Syndrome; Tooth

Three cases of de Lange's syndrome are described. This condition is characterized by generally severe mental retardation, reduced stature, mild microcephaly, hypertrichosis, various anomalies of hands and feet, and a peculiar facies. The most outstanding features of the latter are the low forehead, profuse, generally confluent eyebrows, abundant long eyelashes, eyes that frequently slant downwards and outwards in antimongoloid fashion, pug nose with prominent anteverted nostrils, increased distance between nose and vermilion border of upper lip, slight reduction in size of chin, and often abnormally low-placed ears. The etiology of de Lange's syndrome is at present unknown.

Topics: Adolescent; Body Height; Child; Congenital Abnormalities; De Lange Syndrome; Ear Deformities, Acquired; Ear, External; Eye; Eyebrows; Facial Expression; Hand Deformities; Hirsutism; Humans; Hypertrichosis; Intellectual Disability; Lip; Mandible; Microcephaly; Nose; Nose Deformities, Acquired

Topics: Adolescent; Child; Cleft Lip; Cleft Palate; Congenital Abnormalities; Finger Injuries; Foot Diseases; Hand Deformities; Humans; Infant; Infant, Newborn; Infant, Newborn, Diseases; Meningocele; Nose; Nose Deformities, Acquired; Plastics; Surgery, Plastic