. 21 . 21.2 The Ichthyoses 21 Genodermatoses Although this chapter is devoted to genodermatoses, many acquired disorders are also considered when they seem to fit into the general clinical picture. For example, acquired forms of porokeratosis are considered along with the less common in- herited ones. Genodermatoses 21.1 MIM Code What..................................................................................... is the MIM Code? Victor A. McKusick, one of the giants of clinical human genetics, started using a numerical code when he began compiling his books entitled Mendelian Inheritance in Man. The books evolved into a website, OMIM (Online Mendelian Inheritance in Man), which today serves as the standard for clinical genetics and the most convenient way to acquire updated information on all genetic disorders. The MIM code is given throughout this book whenever it is relevant. The first digit identifies the pattern of diagnosis: 1 = autosomal dominant inheritance; 2 = auto- somal recessive inheritance; 3 = X-linked inheritance. .....................................................................................How to Use OMIM 1 Simply enter ONIM in Google or any search engine and you will land on OMIM—or enter www.ncbi.nlm.nih.gov/OMIM. 2 Search OMIM. 3 Enter the MIM code, or a key word or two if you are looking for a syndrome or set of findings. 4 You will see a list of disease descriptions likely to be relevant to your query; chose whichever ones seem most useful. 5 Now you can read an update about the disease, the gene, find extensive references, or be linked to Medline. 21.2 The Ichthyoses Overview..................................................................................... The primary ichthyoses are a heterogenous group of inherited disorders featuring ex- cessive scale. The alternate term disorder of keratinization is less offensive to patients who do not enjoy being told they resemble fish (ichthyosis is Greek for “fishlike con- dition”). Secondary or acquired ichthyosis describes similar scaly conditions appear- ing later in life. The “brick and mortar” model of the epidermis helps one understand the genetic basis of the primary ichthyoses. The stratum corneum is made up of keratins and lipids. Mutations in keratins usually have autosomal dominant inheritance and can be viewed as “defective bricks.” Mutations in the enzymes needed to produce and metabolize lipids are usually autosomal recessive, and represent “defective mortar.” . 332 Sterry, Dermatology © 2006 Thieme All rights reserved. Usage subject to terms and conditions of license. 21.2 The Ichthyoses . 21 Classification..................................................................................... ̈ Primary ichthyoses: ț Common: – Ichthyosis vulgaris (see below). – X-linked recessive ichthyosis. ț Rare: – Congenital autosomal recessive ichthyoses: Genodermatoses – Nonbullous congenital ichthyosiform erythroderma. – Lamellar ichthyosis. – Autosomal dominant lamellar ichthyosis. – Ichthyoses with epidermolytic hyperkeratosis: – Bullous congenital ichthyosiform erythroderma (Brocq). – Ichthyosis hystrix (Curth–Macklin). – Ichthyosis bullosa (Siemens). – Harlequin fetus. – Syndromes with ichthyosis: – Ichthyosis linearis circumflexa (Netherton syndrome). – X-linked dominant chondrodysplasia punctata (Conradi–Hünermann– Happle syndrome). – Refsum syndrome. – Sjögren–Larsson syndrome. ̈ Secondary or acquired ichthyoses: ț Paraneoplastic marker for lymphoma and internal malignancies. Caution: Whenever ichthyosis appears in adult life for the first time, exclude an underlying malignancy. ț Infections: Leprosy, tuberculosis, syphilis. ț Vitamin deficiency: Vitamin A, vitamin B6, and nicotinic acid deficiency (pella- gra, p. 302). ț Medications: nicotinic acid (most common), triparanol, butyrophenone. ̈ Note: Any drug that alters lipids is potentially capable of inducing an ichthyo- sis-like condition. ț Miscellaneous: Sarcoidosis, hypothyroidism, Down syndrome, long-term renal dialysis, severe xerosis in the elderly. .....................................................................................Ichthyosis Vulgaris ̈ MIM code: 146700. ̈ Definition: Most common form of ichthyosis and also the mildest. ̈ Epidemiology: Prevalence of 1:250. ̈ Pathogenesis: Abnormal formation of keratohyalin granules and delayed de- struction of desmosomes because of defective or absent production of profilaggrin and filaggrin, producing a retention hyperkeratosis. ̈ Clinical features: ț Usually starts in first year of life (months 3–12; not at birth), progressive until puberty, then usually improvement. Better in summer. ț Clinically overlaps with xerosis, sometimes making definitive diagnosis diffi- cult. ț White fine scales of varying intensity on extensor surfaces (especially shins), trunk and lateral aspects of face. Flexures always spared (Fig. 21.1). No mucosal involvement. ț Exaggerated palmoplantar markings (ichthyosis hand or foot). ț Callus-like lesions on knees and elbows. 333 . Sterry, Dermatology © 2006 Thieme All rights reserved. Usage subject to terms and conditions of license. 21 . 21.2 The Ichthyoses Cheeks (in childhood) Keratosis pilaris Genodermatoses Sparing of flexures Keratosis pilaris Sparing of flexures a Fig. 21.1 · Ichthyosis vulgaris. a Locali- b zation. b Appearance. ț Follicular hyperkeratoses on shoulders (keratosis pilaris); sometimes also in- volves buttocks, thighs and upper arms. ̈ Note: When confronted with extensive keratosis pilaris, always think of ichthy- osis vulgaris. ț Associated disorder: Atopic dermatitis (50%). ̈ Histology: Mild hyperkeratosis with an absent granular layer; normal dermis. ̈ Diagnostic approach: Clinical examination; biopsy may be helpful, but often equivocal. Best clues are family history, early onset, spared flexures, and hyper- linear palms. 334 Sterry, Dermatology © 2006 Thieme All rights reserved. Usage subject to terms and conditions of license. 21.2 The Ichthyoses . 21 ̈ Differential diagnosis: Other forms of ichthyosis, acquired ichthyosis, extreme xerosis (particular problem in blacks). ̈ Therapy: Topical urea compounds most useful; watch concentration (irritating if too high) and chose a well-tolerated vehicle; alternatives include lactic acid and salicylic acid or combinations thereof. Lubrication of skin after bathing most cru- cial; defatting soaps should be avoided. ̈ Note: Topical corticosteroids absolutely useless—just a very expensive cream! Genodermatoses X-linked..................................................................................... Recessive Ichthyosis ̈ Synonym: Steroid sulfatase deficiency. ̈ MIM code: 308100. ̈ Definition: Ichthyosis seen only in men as a result of steroid sulfatase deficiency. ̈ Epidemiology: Prevalence of 1:6000 among men. ̈ Pathogenesis: Mutation in steroid sulfatase gene STS at Xp22.32 means that the mortar (cholesterol sulfate) cannot be broken down, so once again a retention hy- perkeratosis develops. ̈ Clinical features: ț Ichthyosis (100%): – Starts in first 6months, progressive until puberty, then stable; improves in summer. – Large brown polygonal scales divided by wide splits (Fig. 21.2). Fig. 21.2·X-linked recessive ichthyosis: coarse brown scales. – In younger patients, prominent involvement of scalp, ears, and neck (dirty neck). – On trunk and extremities, typically localized severally involved areas. ț Ocular involvement (100%): – Asymptomatic corneal opacities. – May also be found in carrier females. ț Complications of pregnancy (30–40%): – Deficiency of placental steroid sulfatase leads to low levels of estrogens. – Often delayed onset of labor or inadequate contractions. ț Hypogonadism (25%): – Reduced androgen synthesis leads to hypergonadotropic hypogonadism. – Testes often undescended with increased risk of testicular carcinoma. ̈ Histology: Hyperkeratosis, normal to thickened granular layer. ̈ Diagnostic approach: ț Clinical examination (dirty neck), history of abnormal delivery or affected un- cles; elevated plasma cholesterol sulfate level or lipoprotein electrophoresis showing increasing motility of - and pre--lipoproteins. ț Also arrange for ophthalmologic and urologic consultation; consider testost- erone replacement. 335 . Sterry, Dermatology © 2006 Thieme All rights reserved. Usage subject to terms and conditions of license. 21 . 21.2 The Ichthyoses ̈ Differential diagnosis: In contrast to ichthyosis vulgaris, no hyperlinear palms, no keratosis pilaris, flexural involvement and larger, darker scales. ̈ Therapy: Same as ichthyosis vulgaris; also worth trying 10% cholesterol oint- ments topically, especially in infants who do not tolerate urea or lactic acid. Collodion..................................................................................... Baby A number of forms of ichthyosis present at birth with infant encased in a tight mem- Genodermatoses brane of adherent keratinocytes, which has been compared to parchment or col- lodion. Kollodes is the Greek word for glutinous or glue-like. The membrane is then shed, leaving either normal skin (lamellar exfoliation of newborn) or, more often, one of the forms of nonbullous congenital ichthyosiform erythroderma or lamellar ichthyosis. Both disorders are heterogenous and also show overlaps. Our listing and description is deliberately simplified; when confronted with a case, consult OMIM or a specialized text. .....................................................................................Nonbullous Congenital Ichthyosiform Erythroderma ̈ MIM code: 242100. ̈ Definition: