Genetic Skin Disorders Revision Before Exams

Xeroderma Pigmentosum
Severe sunburn after minimal UV exposure with early freckling and multiple skin cancers; autosomal recessive, due to defective nucleotide excision DNA repair (XPA–XPG genes) causing UV damage accumulation, with severe risk of ocular (photophobia, keratitis) and neurological complications.

Oculocutaneous Albinism
Generalized hypopigmentation of skin and hair since birth with nystagmus and reduced vision; autosomal recessive, due to defective melanin synthesis causing reduced pigment production (tyrosinase or OCA2, TYRP1 genes for main types; OCA1 is tyrosinase-deficient).

Epidermolysis Bullosa
Recurrent blisters after minor trauma since birth with family history; autosomal dominant or recessive, due to mutations in structural proteins causing skin fragility, classified by level: simplex (KRT5/14), junctional (LAMA3, LAMB3), dystrophic (COL7A1).

Ichthyosis Vulgaris
Dry fine scaling on extensor surfaces with flexural sparing and atopy; autosomal dominant, due to filaggrin (FLG) gene mutation causing impaired skin barrier, often associated with keratosis pilaris.

Lamellar Ichthyosis
Collodion baby evolving into large dark plate-like scales and severe ectropion; autosomal recessive, due to TGM1 or related keratinization gene mutations causing defective cornification.

Harlequin Ichthyosis
Neonate with thick armor-like plates, ectropion, and eclabium; autosomal recessive, due to ABCA12 gene mutation causing severe lipid barrier defect; now survivable with intensive care.

Neurofibromatosis Type 1
Café-au-lait macules, axillary freckling, neurofibromas, and Lisch nodules; autosomal dominant, due to NF1 gene mutation (chromosome 17) causing RAS pathway dysregulation, with diagnostic NIH criteria requiring ≥2 features.

Neurofibromatosis Type 2
Progressive hearing loss with bilateral vestibular schwannomas and other CNS tumors (meningiomas, ependymomas); autosomal dominant, due to NF2 (merlin) gene mutation (chromosome 22) causing tumor suppressor loss.

Tuberous Sclerosis
Seizures with facial angiofibromas, ash-leaf macules, and periungual fibromas; autosomal dominant, due to TSC1 or TSC2 mutations causing mTOR pathway activation and hamartomas in brain, skin, heart, kidneys.

Incontinentia Pigmenti
Female infant with staged Blaschko-line lesions (vesicular, verrucous, hyperpigmented, atrophic); X-linked dominant (male lethal), due to IKBKG (NEMO) gene mutation causing NF-kB pathway dysregulation.

Pseudoxanthoma Elasticum
Yellow papules in flexures with loose skin and angioid streaks leading to vision loss, and systemic vasculopathy; autosomal recessive, due to ABCC6 gene mutation causing abnormal mineralization of elastic fibers.

Ehlers–Danlos Syndrome
Hyperextensible skin, joint hypermobility, and easy bruising; mostly autosomal dominant, due to defective collagen synthesis or processing causing connective tissue fragility (COL5A1/COL5A2 for classical type; COL3A1 for vascular type - high risk of rupture).

Marfan Syndrome
Tall habitus with lens dislocation and aortic root dilation; autosomal dominant, due to FBN1 (fibrillin-1) gene mutation causing defective microfibril formation, diagnosed via revised Ghent criteria.

Porokeratosis
Annular plaques with raised keratotic borders and cornoid lamella on histology; autosomal dominant, due to defects in keratinocyte differentiation and epidermal barrier causing clonal expansion (e.g., MVK, PMVK genes for different clinical variants).

Darier Disease
Greasy hyperkeratotic papules in seborrheic areas with V-shaped nail notching; autosomal dominant, due to ATP2A2 gene mutation causing disrupted calcium signaling and desmosomal adhesion.

Hailey–Hailey Disease
Recurrent painful flexural erosions worsened by heat and sweating; autosomal dominant, due to ATP2C1 gene mutation causing defective calcium transport and acantholysis (like a 'dilapidated brick wall' histologically).

Pachyonychia Congenita
Thickened dystrophic nails with painful palmoplantar keratoderma and oral leukokeratosis; autosomal dominant, due to keratin gene mutations (KRT6, KRT16, KRT17) causing cytoskeletal instability in epithelial tissues.

Netherton Syndrome
Erythroderma, infections, high IgE, and bamboo hair (trichorrhexis invaginata); autosomal recessive, due to SPINK5 gene mutation causing LEKTI deficiency and profound barrier/immune dysfunction.

Bloom Syndrome
Short stature, photosensitivity, and cancer predisposition with sister chromatid exchanges; autosomal recessive, due to BLM gene mutation causing defective DNA helicase and genomic instability.

Cockayne Syndrome
Growth failure, neurodevelopmental delay, photosensitivity, and premature aging; autosomal recessive, due to ERCC6 or ERCC8 mutations causing defective transcription-coupled DNA repair.

Rothmund–Thomson Syndrome
Early poikiloderma with skeletal defects and osteosarcoma risk; autosomal recessive, due to RECQL4 gene mutation causing defective DNA helicase in most cases (Type 2).

Peutz–Jeghers Syndrome
Mucocutaneous lentigines with hamartomatous GI polyps and increased cancer risk (GI, breast, pancreas); autosomal dominant, due to STK11 gene mutation causing disrupted cell polarity and growth control.

Basal Cell Nevus Syndrome (Gorlin Syndrome)
Multiple basal cell carcinomas with jaw cysts and calcified falx cerebri; autosomal dominant, due to PTCH1 gene mutation causing constitutive Hedgehog pathway activation.

Ataxia Telangiectasia
Cerebellar ataxia, telangiectasia, and recurrent infections with elevated AFP; autosomal recessive, due to ATM gene mutation causing defective DNA damage response, radiosensitivity, and cell cycle defects.

Alkaptonuria

Dark urine on standing with ochronosis of cartilage (ears, sclera) and early arthritis; autosomal recessive, due to HGD gene mutation causing homogentisic acid accumulation.

Fabry Disease

Angiokeratomas, acroparesthesia, and renal involvement leading to ESRD, cardiomyopathy, and stroke; X-linked recessive, due to α-galactosidase A deficiency (GLA gene).

Kindler Syndrome

Trauma-induced blistering with progressive poikiloderma and photosensitivity; autosomal recessive, due to FERMT1 gene mutation affecting actin-ECM linkage.

Hermansky–Pudlak Syndrome

Albinism with bleeding tendency due to platelet dysfunction and ceroid lipofuscinosis causing pulmonary fibrosis/colitis; autosomal recessive, due to HPS gene mutations affecting lysosome-related organelles.

Griscelli Syndrome

Silvery-gray hair with hypopigmentation and immunodeficiency or neurological impairment depending on type; autosomal recessive, due to RAB27A (Type 2, hemophagocytic risk) or MYO5A (Type 1, neurological) mutations.

Waardenburg Syndrome

Congenital deafness with white forelock and patchy depigmentation and heterochromia iridum; autosomal dominant, due to PAX3 or related gene mutations affecting neural crest development.

Piebaldism

Congenital stable depigmented patches with white forelock and normal texture skin; autosomal dominant, due to KIT gene mutation affecting melanocyte migration causing absence of melanocytes in involved skin.

Dyschromatosis Universalis Hereditaria

Generalized mottled hyper- and hypopigmented macules from early childhood; autosomal dominant or recessive, due to ADAR gene mutation affecting RNA editing causing pigmentary mosaicism.

Dyschromatosis Symmetrica Hereditaria

Symmetric hyper- and hypopigmented macules on dorsal hands and feet sparing trunk; autosomal dominant, due to ADAR1 mutation affecting melanocyte function causing acral dyschromia.

Hypomelanosis of Ito

Hypopigmented streaks along Blaschko lines with neurological or skeletal anomalies; sporadic mosaicism, due to postzygotic chromosomal mosaicism affecting melanocyte distribution causing patterned hypopigmentation.

Linear and Whorled Nevoid Hypermelanosis

Swirling hyperpigmented macules present at birth without inflammation; somatic mosaicism, due to postzygotic mutation affecting melanocyte proliferation causing linear hyperpigmentation.

Ocular Albinism

Normal skin pigmentation with nystagmus, photophobia, and hypopigmented fundus; X-linked recessive, due to GPR143 mutation affecting melanosome transport causing ocular hypopigmentation.

Familial Atypical Multiple Mole Melanoma Syndrome

Multiple dysplastic nevi with early-onset melanoma risk; autosomal dominant, due to CDKN2A mutation affecting cell-cycle regulation causing melanoma predisposition.

Sturge–Weber Syndrome

Facial port-wine stain in trigeminal distribution with seizures and glaucoma; sporadic mosaic, due to GNAQ mutation affecting vascular development causing capillary malformations in the skin (port-wine stain), leptomeninges (seizures, hemiparesis), and eye (glaucoma).

Hereditary Hemorrhagic Telangiectasia

Mucocutaneous telangiectasia with recurrent epistaxis and AVMs; autosomal dominant, due to ENG (Type 1) or ACVRL1 (Type 2) mutation affecting TGF-β signaling causing abnormal angiogenesis.

Hypohidrotic Ectodermal Dysplasia

Sparse hair, missing teeth, and reduced sweating with heat intolerance; X-linked recessive (most common) or autosomal, due to EDA/EDAR mutation affecting ectodermal development causing sweat gland aplasia and characteristic facies (frontal bossing, depressed nasal bridge).

Hidrotic Ectodermal Dysplasia (Clouston Syndrome)

Nail dystrophy, palmoplantar keratoderma, and alopecia without hypohidrosis; autosomal dominant, due to GJB6 mutation affecting connexin channels causing ectodermal dysfunction.

Naegeli–Franceschetti–Jadassohn Syndrome

Reticulate hyperpigmentation, absent dermatoglyphics, enamel defects; autosomal dominant, due to KRT14 mutation affecting basal keratinocytes causing pigmentary reticulation.

Dermatopathia Pigmentosa Reticularis

Generalized reticulate hyperpigmentation with alopecia and nail dystrophy; autosomal dominant, due to KRT14 mutation affecting epidermal integrity causing pigmentary network changes.

EEC Syndrome

Split hand-foot malformations with ectodermal dysplasia and cleft lip/palate; autosomal dominant, due to TP63 mutation affecting ectodermal differentiation causing limb and skin defects.

Aplasia Cutis Congenita

Congenital absence of skin commonly on scalp; sporadic or autosomal dominant, due to defective skin morphogenesis affecting fetal skin development causing localized skin absence.

Adams–Oliver Syndrome

Scalp defects with limb abnormalities and vascular anomalies; autosomal dominant or recessive, due to ARHGAP31 or DOCK6 mutation affecting cytoskeletal signaling causing scalp and limb malformations.

Cutis Laxa

Loose, sagging inelastic skin with systemic involvement; autosomal dominant or recessive, due to ELN or ATP6V0A2 mutation affecting elastic fiber formation causing skin laxity and systemic complications (emphysema, hernias, vascular aneurysms).

Pseudohypoparathyroidism

Round facies, brachydactyly, subcutaneous ossifications; autosomal dominant, due to GNAS mutation affecting PTH signaling causing Albright hereditary osteodystrophy.

Multiple Endocrine Neoplasia Type 2B

Mucosal neuromas, marfanoid habitus, medullary thyroid carcinoma; autosomal dominant, due to RET mutation affecting tyrosine kinase signaling causing neural crest tumors.

Cowden Syndrome

Trichilemmomas with oral papillomas and breast/thyroid cancer risk; autosomal dominant, due to PTEN mutation affecting PI3K-AKT signaling causing hamartoma formation.

LEOPARD Syndrome

Multiple lentigines with ECG defects and hypertelorism; autosomal dominant, due to PTPN11 mutation affecting RAS-MAPK pathway causing pigmentary and cardiac anomalies. Acronym: Lentigines, ECG abnormalities, Ocular hypertelorism, Pulmonic stenosis, Abnormal genitalia, Retardation of growth, Deafness.

Carney Complex

Spotty pigmentation, myxomas, and endocrine tumors; autosomal dominant, due to PRKAR1A mutation affecting cAMP signaling causing tumor predisposition.

Basex–Dupré–Christol Syndrome

Early-onset basal cell carcinomas with hypotrichosis and follicular atrophoderma; X-linked dominant, due to ACTRT1 mutation affecting Hedgehog signaling causing follicular defects.

Epidermal Nevus Syndrome

Linear epidermal nevi with neurologic and skeletal anomalies; mosaic, due to postzygotic FGFR3 or HRAS mutation affecting epidermal proliferation causing nevus formation.

Proteus Syndrome

Asymmetric overgrowth with cerebriform connective tissue nevi; sporadic mosaic, due to AKT1 mutation affecting cell growth pathways causing segmental overgrowth.

Schimmelpenning Syndrome

Sebaceous nevi with seizures and ocular defects; mosaic, due to postzygotic HRAS/KRAS mutation affecting ectodermal development causing neurocutaneous syndrome.

Goltz Syndrome

Linear skin atrophy with skeletal and ocular defects; X-linked dominant, due to PORCN mutation affecting Wnt signaling causing focal dermal hypoplasia.

Conradi–Hünermann Syndrome

Ichthyosiform erythroderma with skeletal asymmetry and cataracts; X-linked dominant, due to EBP mutation affecting cholesterol biosynthesis causing chondrodysplasia punctata.

Sjögren–Larsson Syndrome

Ichthyosis with spastic diplegia and intellectual disability; autosomal recessive, due to ALDH3A2 mutation affecting fatty aldehyde metabolism causing neurocutaneous disease.

Refsum Disease

Ichthyosis with neuropathy, ataxia, and retinitis pigmentosa; autosomal recessive, due to PHYH mutation affecting phytanic acid metabolism causing lipid accumulation.

Menkes Disease

Sparse kinky hair with neurodegeneration and failure to thrive; X-linked recessive, due to ATP7A mutation affecting copper transport causing enzyme dysfunction. "Kinky hair" is pili torti; low serum copper & ceruloplasmin.

Björnstad Syndrome

Pili torti with sensorineural deafness; autosomal recessive, due to BCS1L mutation affecting mitochondrial function causing hair shaft defects.

Trichothiodystrophy

Brittle sulfur-deficient hair with photosensitivity and neurodelay; autosomal recessive, due to ERCC2 mutation affecting DNA repair causing hair fragility.

Monilethrix

Beaded fragile hair with alopecia; autosomal dominant, due to KRT81/83/86 mutation affecting hair shaft keratin causing periodic constrictions.

Trichorrhexis Invaginata

Bamboo hair with atopic diathesis; autosomal recessive, due to SPINK5 mutation affecting protease inhibition causing hair shaft invagination.

Lipoid Proteinosis

Hoarseness with beaded eyelid papules and scarring; autosomal recessive, due to ECM1 mutation affecting extracellular matrix causing hyaline deposition.

Papillon–Lefèvre Syndrome

Palmoplantar keratoderma with early periodontitis; autosomal recessive, due to CTSC mutation affecting neutrophil function causing periodontal destruction.

Olmsted Syndrome

Severe mutilating palmoplantar keratoderma with periorificial plaques; autosomal dominant or sporadic, due to TRPV3 mutation affecting keratinocyte signaling causing hyperkeratosis.

IFAP Syndrome

Ichthyosis follicularis with alopecia and photophobia; X-linked recessive, due to MBTPS2 mutation affecting cholesterol homeostasis causing follicular keratinization.

KID Syndrome

Keratitis, ichthyosis, and deafness; autosomal dominant, due to GJB2 mutation affecting connexin 26 causing epidermal barrier dysfunction.

Loricrin Keratoderma

Palmoplantar keratoderma with ichthyosis; autosomal dominant, due to LOR mutation affecting cornified envelope formation causing hyperkeratosis.

Mal de Meleda

Diffuse palmoplantar keratoderma extending beyond borders; autosomal recessive, due to SLURP1 mutation affecting keratinocyte adhesion causing severe PPK.

Erythrokeratodermia Variabilis

Migratory erythematous plaques with fixed hyperkeratosis; autosomal dominant, due to GJB3/GJB4 mutation affecting gap junctions causing keratinization defects.

Vohwinkel Syndrome

Honeycomb palmoplantar keratoderma with constricting bands; autosomal dominant, due to GJB2 mutation affecting connexins causing digital autoamputation.

CHILD Syndrome

Unilateral ichthyosiform nevus with limb defects; X-linked dominant, due to NSDHL mutation affecting cholesterol synthesis causing hemidysplasia.

Acrokeratosis Verruciformis

Flat wart-like papules on hands and feet; autosomal dominant, due to ATP2A2 mutation affecting calcium pumps causing epidermal dyskeratosis.

Buschke–Ollendorff Syndrome

Elastic tissue nevi with osteopoikilosis; autosomal dominant, due to LEMD3 mutation affecting TGF-β signaling causing connective tissue nevi.

PXE-like Syndrome with Coagulation Defect

PXE-like skin with bleeding tendency; autosomal recessive, due to GGCX mutation affecting vitamin K–dependent carboxylation causing elastic fiber calcification.

Wiedemann–Steiner Syndrome

Hypertrichosis cubiti with intellectual disability; autosomal dominant, due to KMT2A mutation affecting histone methylation causing hair overgrowth.