Other Conditions

Palmoplantar Keratodermas (see Tables 2-6, 2-7)
Ectodermal Dysplasias (see Table 2-8)
Metabolic and Enzyme Deficiency Diseases (Table 2-9)
Signs of Spinal Dysraphism (Table 2-10)
Keratinopathies (Table 2-11)

Table 2-6 Diffuse Palmoplantar Keratodermas   Disease   Type   Inh   Mutation   Clinical Appearance   Non-epidermolytic PPK (Unna-Thost Syndrome) Diffuse AD K1 PPK with erythematous border, hyperhidrosis, secondary tinea infections, pitted keratolysis, no transgrediens   Epidermolytic PPK (Vörner Syndrome) Epidermolytic AD K1 or K9 (most common) Clinically similar to nonepidermolytic PPK but histology shows epidermolytic hyperkeratosis   Mal de Meleda Transgredient AR SLURP-1 gene (encodes protein: Secreted Ly-6/uPar related protein) Transgredient PPK (hands, feet, elbows, knees), hyperhidrosis with malodor and secondary infections, perioral erythema, thickened nails   Vohwinkel Syndrome, Classic (Keratoderma Hereditaria Mutilans) Mutilating keratoderma + deafness AD GJB2 (encodes connexin 26) Diffuse honeycomb-like PPK, pseudoainhum, starfishshaped keratoses of joints, sensorineural deafness, linear keratotic plaques of knees, scarring alopecia   Vohwinkel Syndrome, Variant Mutilating + ichthyosis AD Loricrin (cornified envelope protein) Similar to classic Vohwinkel, but no deafness and more generalized ichthyosis   Papillon–Lefèvre Syndrome PPK + periodontitis AR Cathepsin C (lysosomal protease) Periodontitis, early loss of teeth, transgredient erythematous PPK with psoriasiform lesions on extremities, calcification of falx/tentorium, hyperhidrosis   Haim–Munk Syndrome PPK + periodontitis + onychogryphosis AR Cathepsin C Papillon–Lefevre syndrome + onychogryphosis, arachnodactyly, acroosteolysis   Naxos Disease PPK + woolly hair + cardiomyopathy AR Plakoglobin Woolly hair, right ventricular cardiomyopathy with arrhythmias, PPK   Carvajal Syndrome PPK + woolly hair + cardiomyopathy AR Desmoplakin Dilated cardiomyopathy, PPK in first year of life, woolly hair   Olmsted Syndrome Mutilating PPK + periorificial plaques ? ? (possible K5 and K14) PPK (initially focal, then widespread) leading to flexion deformities, autoamputation, erythematous hyperkeratotic perioral plaques   Non-epidermolytic PPK with deafness PPK + sensorineural deafness ? Connexin 26 or A7445G (mitochondrial) PPK, progressive sensorineural deafness

Table 2-7 Focal Palmoplantar Keratodermas   Disease   Inh   Mutation   Clinical Appearance   Howel–Evans Syndrome AD TOC gene (tylosis-oesophageal carcinoma) Focal PPK over pressure areas (balls of feet > hands), oral leukokeratosis, ↑ esophageal CA   Richner–Hanhart Syndrome (Tyrosinemia Type II) AR Hepatic tyrosine amino-transferase (TAT) Pseudoherpetic keratitis, dendritic corneal ulcers (tyrosine crystal deposition in eyes), painful focal PPK, progressive MR, treat with dietrestricted in tyrosine and phenylalanine   Punctate PPK (Keratosis Punctata Palmaris Et Plantaris) AD ? Begins during or near adolescence, punctate keratoses on palms, can also occur in palmar creases of patients of African origin   Acrokeratoelastoidosis AD Skin-colored papules involving hands and feet   Striate PPK AD Desmoglein 1 and desmoplakin 1 Onset in teens/early adulthood, hyperkeratotic linear plaques on volar fingers, diffuse/focal plaques on proximal palms/soles   Erythrokeratoderma Variabilis (Mendes da Costa) AD GJB3, GJB4 (connexin 30.3 and 31) Erythematous migratory patches (may last minutes to days), fixed hyperkeratotic plaques, 50% with PPK, flexures spared   Progressive Symmetric Erythrokeratoderma AD Likely loricrin mutation or connexin 31 Fixed hyperkeratotic erythematous plaques over joints/extremities, 50% with PPK

Table 2-8 Ectodermal Dysplasias   Disease   Inh   Mutation   Clinical Appearance   Hidrotic Ectodermal Dysplasia (Clouston Syndrome) AD GJB6 (connexin 30) Hypotrichosis, diffuse PPK, nail dystrophy, NORMAL teeth and sweating, MR, ocular abnormalities   Hypohidrotic (Anhidrotic) Ectodermal Dysplasia (Christ-Siemens-Touraine) XR EDA (ectodysplasin A) Hypotrichosis, periorbital hyperpigmentation, ABSENT or conical teeth, sweating with heat intolerance, NORMAL nails, saddle nose, everted thick lips, ↑ bronchopulmonary infections   AD, AR EDAR gene (ED-A receptor)   Ankyloblepharon-Ectodermal Dysplasia-Clefting Syndrome (AEC) (Hay-Wells) AD p63 Chronic erosive scalp dermatitis, abnormal granulation tissue, recurrent bacterial infections, ankyloblepharon, hypotrichosis, 80% cleft lip/palate   Ectodermal Dysplasia- Ectrodactyly-Clefting Syndrome (EEC) (Split Hand-Split Foot- Ectodermal Dysplasia-Clefting) AD p63 Ectrodactyly (split hand/foot), hearing loss, nail dystrophy, ± PPK, 70% cleft lip/palate, sparse and dry hair, hypodontia   Rapp-Hodgkin Syndrome AD Mid facial hypoplasia, cleft lip/palate, scalp dermatitis, ↓ sweating, nail dystrophy, hypodontia   Ectodermal Dysplasia/Skin Fragility Syndrome AR Plakophilin-1 Trauma-induced bullae (most prominent during infancy), sparse hair, thick dystrophic nails

Table 2-9 Metabolic and Enzyme Deficiency Diseases   Disease   Inh   Defect   Clinical Findings   Alkaptonuria AR Homogentisic acid (HA) oxidase Blue-gray pigmentation of cartilage (helices), sclera and skin (axilla); urine darkens on standing, arthritis   Biotinidase Deficiency AR Alopecia, periorificial dermatitis, developmental delay, seizures; treat with biotin   Fabry Disease XLR α-Galactosidase A Glycosphingolipids in vascular endothelium: multiple angiokeratomas, extremity pain/paresthesias, whorl-like corneal and lenticular opacities, birefringent lipid globules in urine (“maltese crosses”), MI, cerebrovascular accident (CVA)   Fabry Disease AR α-Fucosidase Multiple angiokeratomas, coarse facies, growth retardation, dysostosis multiplex, mental retardation   Gaucher Disease AR α-Glucosidase (Glucocerebrosidase) Type I (adult): no CNS findings + diffuse brown skin pigmentation, thrombocytopenia, hepatosplenomegaly (HSM), bone pain, ehrlenmeyer flask deformity of femoral midshaft   Type 2 (infant): no skin findings, severe, rapid death   Type 3 (juvenile): chronic neuropathy   Hartnup Disease AR SLC6A19 ↓ Renal reabsorption of neutral amino acids, pellagra-like dermatosis with photosensitivity, ataxia, tremors   Holocarboxylase Synthetase Deficiency AR Alopecia, perioral/perianal dermatitis, metabolic encephalopathy, metabolic acidosis; treat with biotin   Hunter Disease XLR Iduronidate sulfatase Firm, flesh-colored to white papules coalescing over scapula   Hurler Disease AR α-L-iduronidase Mental retardation (MR), HSM, hernia, opacities, gargoyle-like features   Lesch–Nyhan Syndrome XLR HGPRT deficiency Self-mutilation, orange crystals in the diaper, gout, choreoathetosis, MR   Lipoid Proteinosis AR ECM1 defect Pearly papules, hippocampal calcification, infiltration of deposits on lips and tongue (wooden), hoarseness   Neimann–Pick Disease AR Sphingomyelinase deficiency (SMPD1) Type A: failure to thrive, HSM, neurologic deterioration Type B: minimal neurologic disease, xanthomas, histiocytic infiltration in viscera, psychomotor delay, muscle weakness, blindness (cherry red spots)   Phenylketonuria AR SLC39A4 (zinc transporter) Diffuse hypopigmentation, eczema, MR, sclerodermoid changes, blonde hair, blue eyes, urine and skin with mousy odor   Prolidase Deficiency AR Prolidase Skin fragility, ulceration and scarring over lower extremities, photosensitivity, MR, recurrent infections   Wilson’s Disease AR ATP 7B (ATPase copper transporting enzyme) Copper accumulation in liver/brain/cornea, cirrhosis, blue lunula, Kayser–Fleischer rings, ataxia, dementia, hepatomegaly

Table 2-10 Signs of Spinal Dysraphism (High Risk for Dysraphism if ≥ 2 of the Following)               Hypertrichosis   Dimpling   Skin tags   Tails/pseudotails   Lipomas   Aplasia cutis   Hemangiomas   Dermoid cysts/sinuses   Telangiectasia, capillary malformation, nevi (less likely)

Table 2-11 Keratinopathies Type II Keratin Type I Keratin Location of Expression Associated Disease 1 10 Suprabasal keratinocytes Epidermolytic hyperkeratosis (Bullous CIE) Unna-Thost PPK (K1) Ichthyosis hystrix of Curth-Macklin (K1) 1 9 Palmoplantar, suprabasal keratinocytes Epidermolytic PPK (Vörner) 2 10 Granular and upper spinous layer Ichthyosis bullosa of Siemens 3 12 Cornea Meesmann corneal dystrophy 4 13 Mucosal epithelium White sponge nevus 5 14 Basal keratinocytes Epidermolysis bullosa simplex (EBS) Dowling-Degos disease (K5 alone) 6 16 Outer root sheath Pachyonychia congenita I (Jadassohn Lewandowsky) Focal PPK 6 17 Nail bed Pachyonychia congenita II (Jackson-Lawler) Steatocystoma multiplex 8 18 Simple epithelium Cryptogenic cirrhosis K81 and K86 Hair Monilethrix 19 Simple epithelium, bulge cells 6 16 Hyperproliferative keratinocytes