63 - Other Genodermatoses

Abstract

63a: Other Genodermatoses: Disorders Featuring TumorigenesisThis section focuses on genetic tumor predisposition syndromes that have characteristic mucocutaneous manifestations. Recognition of these skin findings facilitates diagnosis and surveillance for associated extracutaneous malignancies and endocrine abnormalities. Multiple endocrine neoplasia, PTEN hamartoma tumor syndrome (including Cowden syndrome), Gardner syndrome, and Muir–Torre syndrome are reviewed in detail.63b: Other Genodermatoses: Enzyme Deficiency DiseasesThis section provides an overview of enzyme deficiency diseases with skin findings that represent diagnostic clues. The diverse cutaneous features include discoloration, dermatitis, angiokeratomas, and sclerosis; adnexal manifestations such as hypohidrosis and alopecia may also be observed. Extracutaneous manifestations and current management strategies are highlighted. Conditions covered include defects in amino acid metabolism/transport, multiple carboxylase deficiency, lysosomal storage diseases, and mitochondrial disorders.63c: Other Genodermatoses: Premature Aging Syndromes and PoikilodermasThe classic premature aging syndromes are Hutchinson–Gilford progeria and Werner syndromes. However, additional rare disorders can be viewed as progeroid syndromes. Examples include MDPL (mandibular hypoplasia, deafness, progeroid features, and lipodystrophy) syndrome and Néstor–Guillermo progeria syndrome. Understanding the underlying pathophysiology of progeria has led to insights into the group of disorders referred to as laminopathies as well as physiologic aging. This section also reviews disorders in which patients develop poikiloderma.63d: Other Genodermatoses: Ectodermal DysplasiasEctodermal dysplasias are a diverse group of heritable disorders that share the primary feature of abnormalities in at least two of the major ectodermally derived structures – hair, teeth, nails, and sweat glands. Other ectodermal structures, such as mucous and sebaceous glands, are also frequently affected. The various forms of ectodermal dysplasia are distinguished based on the types of ectodermal abnormalities, presence of other cutaneous and extracutaneous manifestations, mode of inheritance, and underlying genetic defect. Ectodysplasin, WNT, and p63 signaling pathways have been implicated in the pathogenesis of both ectodermal dysplasias and inherited abnormalities limited to a single structure (e.g. hair, nails).