isotretinoin and Intellectual-Disability

Principles and mechanisms of neurobehavioral teratogenesis are used to show commonalities between manifestations of abnormal development consequent to genetic abnormality or teratogenic exposure. A comparison and contrast of both the neuropathological and neuropsychological characteristics of children with early embryonic exposure to isotretinoin (Accutane) or with selected mental retardation syndromes is presented. Putative mechanisms of retinoid teratogenesis through the disruption of normal retinoid-triggered embryogenesis and the alteration of homeobox gene expression are discussed. Interference with homeobox gene expression as an avenue to the perturbation of early developmental processes and the production of hindbrain and craniofacial abnormalities is then proposed as a common basis for the translation and expression of several genetic mental retardation syndromes. Finally, dose-response effects and other modulators of vulnerability to abnormal development are used to provide a conceptual framework for the understanding of variability in the expression of genetically caused abnormalities.

Topics: Child; Female; Fragile X Syndrome; Humans; Intellectual Disability; Isotretinoin; Nervous System Diseases; Pregnancy; Teratogens; Williams Syndrome

Tyrosinemia II is caused by a deficiency of hepatic tyrosine aminotransferase. With the deficiency of this key enzyme of tyrosine catabolism there is an increase in plasma tyrosine and then an increase in tyrosine metabolites in the urine. The increased plasma tyrosine causes tyrosine to crystallize in the cornea, producing corneal ulcerations and sometimes proliferation of corneal epithelium. In the epidermis of the palms and soles, tyrosine leads to erosions, crusting, and then hyperkeratosis. The human disease is due to an autosomal recessive gene, and similar genetic diseases have been found in mink and in dogs. A nutritional model for the disease, in which a high-tyrosine low-protein diet is fed to rats, produces almost identical features. The features of this disorder and some of the implications of this disease for the study of other genetic diseases is discussed in this review.

Topics: Adolescent; Amino Acid Metabolism, Inborn Errors; Animals; Ascorbic Acid; Child; Child, Preschool; Eye; Female; Genetic Carrier Screening; History, 20th Century; Humans; Infant; Infant, Newborn; Intellectual Disability; Isomerism; Isotretinoin; Male; Pyridoxine; Rats; Skin; Tretinoin; Tyrosine; Tyrosine Transaminase

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

Many adolescents are sexually active and reproductive health is an important aspect of adolescent medicine. However, pediatricians are often uncomfortable with the issues of sexuality and contraception, for which they have not been particularly trained. The general purpose of this article is to increase pediatricians' sense of competence with adolescents, particularly when having to deal with or counsel on such a sensitive issue as contraception. This second of two parts addresses confidentiality and prescription of oral contraceptives to minors, how to ask questions about sexual and reproductive life, best initial choice and eventual subsequent switch of contraceptive pill, acne and oral contraception, problems with mental handicap, and finally, what about boys. Pediatricians interested in the care of adolescents are strongly invited to keep developing their expertise in the field of sexuality, contraception and reproductive health.

Topics: Acne Vulgaris; Adolescent; Adolescent Behavior; Adolescent Medicine; Contraception; Contraceptives, Oral; Dermatologic Agents; Ethics, Medical; Female; Humans; Intellectual Disability; Isotretinoin; Male; Pediatrics; Physician-Patient Relations; Pregnancy; Pregnancy, Unwanted; Sexual Behavior; Sexuality; Surveys and Questionnaires