isotretinoin and Abnormalities--Multiple

Topics: Abnormalities, Drug-Induced; Abnormalities, Multiple; Female; Fetus; Humans; Infant, Newborn; Isotretinoin; Neural Crest; Pregnancy; Prenatal Exposure Delayed Effects; Tretinoin

Retinoids are synthetic vitamin A derivatives, particularly used in dermatology. Their prescription in women of childbearing age can cause, if pregnancy occurs, a serious malformative embryopathy, mainly involving external ear, brain and heart. A neonatal case caused by isotretinoin (RoAccutane) emphasizes the clinical and epidemiological data concerning this embryopathy. The aetiopathological hypothesis of an interaction between isotretinoin and Hox genes is advanced. Prophylactic measures are difficult since neonatal reported cases are uncommon, but antenatal exposition to this strong teratogenic agent results in multiple spontaneous abortions or pregnancy interruptions.

Topics: Abnormalities, Multiple; Adult; Brain; Ear, External; Female; Heart Defects, Congenital; Humans; Infant, Newborn; Isotretinoin; Pregnancy; Prenatal Exposure Delayed Effects; Teratogens

Although a well-known recommended treatment option, there are currently no studies that describe the detailed regimen of isotretinoin for the treatment of primary keratosis pilaris. Based on previous studies involving other hyperkeratotic disorders, this report describes a safe and effective treatment course of isotretinoin for severe keratosis pilaris.

Topics: Abnormalities, Multiple; Adolescent; Darier Disease; Dermatologic Agents; Drug Administration Schedule; Eyebrows; Female; Humans; Isotretinoin; Treatment Outcome

Koolen-de Vries syndrome (KdVS) is a rare disorder caused by haploinsufficiency of KAT8 regulatory NSL complex subunit 1 (KANSL1), which is characterized by intellectual disability, heart failure, hypotonia, and congenital malformations. To date, no effective treatment has been found for KdVS, largely due to its unknown pathogenesis. Using siRNA screening, we identified KANSL1 as an essential gene for autophagy. Mechanistic study shows that KANSL1 modulates autophagosome-lysosome fusion for cargo degradation via transcriptional regulation of autophagosomal gene, STX17. Kansl1

Topics: Abnormalities, Multiple; Animals; Autophagosomes; Cerebral Cortex; Chromosome Deletion; Chromosomes, Human, Pair 17; Disease Models, Animal; Female; Haploinsufficiency; HeLa Cells; Humans; Intellectual Disability; Isotretinoin; Lysosomes; Mice; Mice, Transgenic; Mitophagy; Neurons; Nuclear Proteins; Primary Cell Culture

Topics: Abnormalities, Multiple; Adult; Amniotic Band Syndrome; Chromosome Aberrations; Connexin 26; Deafness; DNA Mutational Analysis; Female; Fingers; Genes, Dominant; Hand Deformities, Congenital; Hearing Loss, Sensorineural; Humans; Ischemia; Isotretinoin; Keratoderma, Palmoplantar; Membrane Proteins; Phenotype; Toes

Isotretinoin is a drug used for treating severe cystic/nodular acne. Severe malformations have been documented in neonates whose mothers had taken isotretinoin during pregnancy. Women who became pregnant one cycle after completing therapy are believed to be at teratogenic risk not higher than baseline. We describe the case of a newborn whose mother had taken the drug for 4 weeks. The woman then had contraception for 4 weeks (after the drug treatment had finished), and became pregnant after that period. The newborn had isolated bilateral microtia due to suspected isotretinoin exposure. His mother also had a history of urine tract infection in the second week of pregnancy that was treated with cephalexin. The parents were not from a consanguineous marriage and had no family history of congenital malformations. To reduce the risk, effective contraception should be continued in fertile women more than 1 month after completing therapy.

Topics: Abnormalities, Multiple; Apgar Score; Cerebellar Vermis; Cesarean Section; Cisterna Magna; Congenital Microtia; Dermatologic Agents; Female; Humans; Infant, Newborn; Iran; Isotretinoin; Male; Maternal-Fetal Exchange; Polyhydramnios; Pregnancy; Teratogens; Term Birth

Topics: Abnormalities, Multiple; Adolescent; Hair Diseases; Humans; Isotretinoin; Male; Skin Diseases; Syndrome; Treatment Outcome

Retinoic acid is a widely used drug in the treatment of cystic acne. It has teratogenic effects that depend on the gestational period in which it is used. We report a seven months old female whose mother was exposed to retinoic acid in both pre-gestational and gestational periods. She had a retardation of psychomotor development and a brain MRI showed frontal atrophy and a malformation of the posterior fossa. We discuss the mechanisms of the teratogenic effects of retinoic acid.

Topics: Abnormalities, Drug-Induced; Abnormalities, Multiple; Acne Vulgaris; Atrophy; Cranial Fossa, Posterior; Craniofacial Abnormalities; Female; Frontal Lobe; Humans; Infant; Isotretinoin; Keratolytic Agents; Maternal Exposure; Pregnancy; Prenatal Exposure Delayed Effects; Psychomotor Disorders; Teratogens; Tretinoin

The aim of the article is to describe the communication development of a child with Fetal Retinoid syndrome (FRS) from six months to seven years of age. Little is known about this rare acquired syndrome and its long-term implications, especially on a child's communication development. A descriptive, ex post facto research design was used to study the participant's communication development from 1996 when the family enrolled in an early communication intervention programme. Annual serial assessments of the participant and her family were conducted and the data were stored in a research database after each assessment. The results are described according to a 4-level assessment framework and indicated consistent, but moderate to minor delays in the participant's communication development with a mild hearing loss in the right ear, associated with ear anomalies. Although prenatal exposure to isotretinoin may have serious effects on the unborn fetus and even cause death, the participant did not display all the symptoms of FRS described in the literature. The favorable family circumstances, early commencement of intervention, and supporting early educational environments were protecting factors that could have contributed positively to the participant's communication development. The importance of knowledge accumulation about rare syndromes such as FRS in Communication Pathology and Audiology is discussed and guidelines for early identification, assessment and treatment applicable to the case are proposed as an intervention option.

Topics: Abnormalities, Drug-Induced; Abnormalities, Multiple; Child; Child Development; Child, Preschool; Communication; Communication Aids for Disabled; Female; Fetal Diseases; Follow-Up Studies; Humans; Infant; Isotretinoin; Language Development Disorders; Pregnancy; Prenatal Exposure Delayed Effects; Teratogens

Topics: Abnormalities, Drug-Induced; Abnormalities, Multiple; Craniofacial Abnormalities; Humans; Infant; Isotretinoin; Lacrimal Apparatus Diseases; Male; Ophthalmoplegia

Topics: Abnormalities, Multiple; Administration, Oral; Adolescent; Adult; Canada; Female; Fetus; Humans; Isotretinoin; Maternal Exposure; Patient Compliance; Pregnancy; Pregnancy in Adolescence; Program Evaluation; Teratogens

Topics: Abnormalities, Multiple; Administration, Oral; Female; Fetus; Humans; Isotretinoin; Patient Compliance; Pregnancy; Program Evaluation; Teratogens

Vitamin A and its derivatives are known teratogens. To our knowledge, this is the second temporal bone histopathologic report on anomalies related to these substances. A white boy (aged 4 years 5 months at death) was born with a complex central nervous system dysgenesis related to his mother's use of isotretinoin (Accutane) early in pregnancy. Histopathologic examination revealed multiple anomalies in the temporal bones: a narrow external auditory canal, protrusion of bone marrow into the middle ear cavity, anomalies of the ossicles, hypoplasia of the facial nerve, absence of the chorda tympani nerve and the stapedius muscle, anomalies of the membranous labyrinth in the vestibule, a hypoplastic lateral semicircular canal, and a large vestibular aqueduct and endolymphatic sac.

Topics: Abnormalities, Drug-Induced; Abnormalities, Multiple; Child, Preschool; Female; Humans; Isotretinoin; Male; Maternal-Fetal Exchange; Pregnancy; Temporal Bone; Teratogens

Topics: Abnormalities, Drug-Induced; Abnormalities, Multiple; Acne Vulgaris; Fatal Outcome; Humans; Isotretinoin

The extent of clustering of 2 or more defects in the same infant can be expressed as the ratio of the observed number of infants with the defects (O) over the expected number of such infants (E). The expected is usually derived from the product of population rates of individual defects. Because large O/E ratios are obtained for many defect combinations, it has been suggested that clustering of defects is generalized and nonspecific. To control for the tendency of nonspecific clustering of defects, an alternative method is to perform the same calculations among multimalformed infants only. A main limitation of this method is that it adjusts for the clustering tendency of all defects rather than the ones of interest, often resulting in spuriously low O/E ratios. We present a new method to adjust for the tendency for nonspecific clustering between defects that overcomes this limitation. With this method, adjusted O/E ratios are inversely related to the proportion of infants who are multimalformed and have one or more of the defects being examined. Using data from the Metropolitan Atlanta Congenital Defects Program, we apply this method to the previously described associations among VACTERL defects and midline or "schisis" defects. We show that adjusted O/E ratios obtained are greater than those obtained by using multimalformed infants. For midline defects, many of the adjusted ratios were close to one, indicating nonspecific clustering of these defects. Finally, using the example of isotretinoin embryopathy, we show that O/E ratios depend highly on the frequency of exposure in the population, and thus, they should be interpreted with caution.

Topics: Abnormalities, Drug-Induced; Abnormalities, Multiple; Cluster Analysis; Congenital Abnormalities; Humans; Infant, Newborn; Isotretinoin; Mathematics

Acute embryonic exposure to isotretinoin during gastrulation (gestational day 7) in the mouse results in delay or failure of separation of the lens vesicle from the surface ectoderm. During normal lens vesicle detachment, laminin is localized within the lens, keratolenticular stalk and adjacent surface ectoderm. The mesenchyme surrounding the stalk stains positively for fibronectin. In contrast, isotretinoin-exposed embryos at the same stage of gestation exhibit reduced staining for both extracellular matrix components. Persistent keratolenticular attachment observed later in gestation in the exposed embryos is associated with increased production of laminin by the keratolenticular stalk and anterior lens epithelium. A delay in the sequence of production of extracellular matrix may be causally associated with persistence of the keratolenticular stalk.

Topics: Abnormalities, Multiple; Animals; Cornea; Embryo, Mammalian; Female; Fibronectins; Isotretinoin; Laminin; Lens, Crystalline; Mice; Mice, Inbred C57BL

Topics: Abnormalities, Drug-Induced; Abnormalities, Multiple; Female; Humans; Infant, Newborn; Isotretinoin; Male; New Jersey; Teratogens; Tretinoin; United States; United States Food and Drug Administration

Topics: Abnormalities, Drug-Induced; Abnormalities, Multiple; Female; Humans; Infant, Newborn; Isotretinoin; Male; New Jersey; Teratogens; Tretinoin; United States; United States Food and Drug Administration

Topics: Abnormalities, Multiple; Humans; Infant; Isotretinoin; Phenotype; Syndrome; Tretinoin

Vitamin A and vitamin A derivatives have been described as etiologic factors for a number of congenital malformations. Two infants are presented with major auricular malformations including anotia and severe microtia. The infants were products of a pregnancy complicated by Accutane ingestion during the first trimester. Both infants had associated central nervous system malformations. With the increasing use of Accutane for the treatment of cystic acne in young women of child-bearing age, the dangers of teratogenesis in the head and neck area are greatly increased. This presentation will review two such cases as well as give an overview of the embryogenesis and teratogenesis of the auricle.

Topics: Abnormalities, Drug-Induced; Abnormalities, Multiple; Acne Vulgaris; Adult; Ear, External; Female; Humans; Infant, Newborn; Isotretinoin; Male; Teratogens; Tretinoin

Topics: Abnormalities, Multiple; Brain; Brain Diseases; Humans; Isotretinoin; Syndrome; Tomography, X-Ray Computed; Tretinoin

The teratogenicity of vitamin A has been repeatedly reported in the literature and confirmed on the basis of several cases of adverse pregnancy outcome associated with maternal isotretinoin exposure. We report a case which shows a striking similarity with this syndrome, but the child was born to a mother who took a normal supplementation of vitamin A during pregnancy. The differential diagnosis is discussed.

Topics: Abnormalities, Drug-Induced; Abnormalities, Multiple; Adult; Diagnosis, Differential; Female; Humans; Infant, Newborn; Isotretinoin; Phenotype; Pregnancy; Tretinoin; Vitamin A; Vitamins

Isotretinoin, a drug used for the treatment of acne, has been shown to have teratogenic effects. We report an additional case of isotretinoin teratogenicity in which the patient had agenesis of the cerebellar vermis, multiple leptomeningeal neuroglial heterotopias, hydrocephalus, and abnormalities of the corticospinal tracts. These findings are related to those reported previously.

Topics: Abnormalities, Drug-Induced; Abnormalities, Multiple; Acne Vulgaris; Adult; Brain; Female; Humans; Infant, Newborn; Isotretinoin; Teratogens; Tretinoin

Topics: Abnormalities, Drug-Induced; Abnormalities, Multiple; Adolescent; Cerebellum; Ear, External; Face; Female; Humans; Infant, Newborn; Isotretinoin; Male; Pregnancy; Tretinoin

Topics: Abnormalities, Drug-Induced; Abnormalities, Multiple; Female; Humans; Infant, Newborn; Isotretinoin; Maternal-Fetal Exchange; Pregnancy; Tretinoin

13-cis-Retinoic acid, retinyl-mthyl-ether, retinyl-phenyl-ether, retinyl-thio-ether and axerophthene each induced dose-dependent sister-chromatid exchanges (SCE) in human diploid fibroblasts. The functional relationship between retinoid concentration and SCE rate was similar in each of the 5 retinoids tested. The relationship reached a plateau at concentrations exceeding 8 micrograms/ml. alpha-Naphthoflavone (ANF), an inhibitor of P448-dependent mono-oxygenase, prevented the retinoid-induced increase of the SCE rate, but had no inhibitory effect in the presence of 4-nitroquinoline-1-oxide, an ultimate carcinogen. ANF did not reduce the spontaneously increased SCE rate in fibroblasts of patients with Bloom's syndrome. Retinoids failed to induce SCE in V79 Chinese hamster cells, which lack mono-oxygenase. Thus, we conclude that the retinoid-induced SCE rate increases independently of structural changes in the molecular side-chain ad that a metabolic activation of retinoids is required for SCE induction by cytochrome P448-dependent mono-oxygenase.

Topics: Abnormalities, Multiple; Animals; Benzoflavones; Biotransformation; Cell Line; Cricetinae; Cricetulus; Crossing Over, Genetic; Cytochrome P-450 CYP1A2; Cytochromes; Dose-Response Relationship, Drug; Fibroblasts; Humans; Isotretinoin; Mixed Function Oxygenases; Sister Chromatid Exchange; Skin; Structure-Activity Relationship; Telangiectasis; Tretinoin; Vitamin A