High Yield Facts and Buzz Words




(1)
University of Florida, College of Medicine, Gainesville, FL, USA

(2)
Private Practice:, Orlando, FL, USA

 




11.1 Genetic Diseases







































































































































































































































































































































































































Disease

Inh

Gene mutation

Clinical Findings

Acrodermatitis Enteropathica

AR

SLC39A4

Scaly eczematous plaques: perioral, perianal, hands, feet, scalp

AEC Syndrome (Hay-Wells Syndrome)

AD

P63 (p63 protein)

Erosive scalp dermatitis, 80% cleft lip/palate, ankyloblepharon, hypotrichosis

Albinism, Oculocutaneous Type 1

AR

TYR (tyrosinase)

Severe nystagmus, ↑ SCC risk, pink nevi

Albinism, Oculocutaneous Type 2

AR

P (P protein)

Nystagmus, light brown hair, pigmented nevi

Albinism, Oculocutaneous Type 3

AR

TRP-1 (tyrosine-related protein)

Nystagmus, blue/brown iris, light brown hair/skin

Albright Hereditary Osteodystrophy

AD

GNAS1 (encodes α subunit for stimulatory G protein of adenylate cyclase: Gs)

Pseudohypoparathyroidism, short stature, shortened 4th metacarpal, soft tissue calcification and ossification (i.e. osteoma cutis)

Alkaptonuria

AR

HGD (homogentisate oxidase)

Dark urine on standing, ochronosis, valvular heart disease, arthritis, renal calculi, red-black ear wax

Ataxia-Telangiectasia (Louis-Bar Syndrome)

AR

ATM (ataxia-telangiectasia mutated: chromosomal strand break repair)

↑ Leukemia/lymphoma, ↑ sensitivity to ionizing radiation, ↑ sinopulmonary infections, progressive ataxia, telangiectasias

Atrichia with Papules (Congenital Atrichia with Papules)

AR

HR (hairless gene: zinc finger)

Normal hair at birth but not replaced after hair sheds, follicular papules (± resembles keratosis pilaris)

Bannayan-Riley-Ruvacalba Syndrome

AD

PTEN (tumor suppressor gene)

Macrocephaly, lipomas, hemangiomas, genital lentigines, trichilemmomas, ↑ breast/thyroid/GI CA

Bazex Syndrome (Bazex-Dupre-Christol)

XLD

Unknown (gene linked to Xq24-q27)

Multiple BCCs, hypotrichosis, hypohidrosis, follicular atrophoderma (circumscribed areas on dorsal hands/feet)

Beare-Stevenson Cutis Gyrata Syndrome

AD

FGFR2 (fibroblast growth factor receptor 2)

Cutis gyrata, acanthosis nigricans, craniosynostosis (premature fusion of certain bones in skull)

Beckwith-Wiedemann Syndrome

AD (<15%)

CDKN1C (cyclin-dependent kinase inhibitor 1c, aka p57 or Kip2)

Macroglossia, circular depression (helices of ears), gigantism, midline abdominal wall defects, neonatal hypoglycemia, organomegaly, ↑ Wilms tumor

Berardinelli-Seip Syndrome (Congenital Generalized Lipodystrophy)

AR

BSCL2

Acanthosis nigricans, type 2 diabetes mellitus, generalized lipodystrophy

Birt-Hogg-Dubé Syndrome

AD

FLCN (folliculin)

↑ Fibrofolliculomas, trichodiscomas, lipomas, ↑ CA (renal/colon/medullary thyroid), lung cysts

Björnstad Syndrome

AR, AD

BCS1L

Deafness, pili torti

Bloom Syndrome

AR

BLM (RECQL3: DNA helicase)

Oral SCC, leukemia/lymphoma, GI CA, ↑ infections, poikiloderma, photosensitivity, hypogonadism

Brooke-Spiegler Syndrome

AD

CYLD (cylindromatosis)

Multiple trichoepitheliomas, cylindromas, spiradenomas, ± BCCs

Bruton Agammaglobulinemia

XLR

BTK (Bruton tyrosine kinase)

↓ B cells with ↓ Ig levels, eczema resembling atopic dermatitis, recurrent bacterial infections like impetigo/furunculosis (especially encapsulated organisms)

Buschke-Ollendorf Syndrome

AD

LEMD3

Osteopoikilosis, connective tissue nevi (dermatofibrosis lenticularis disseminata)

Carney Complex (LAMB, NAME)

AD

PRKAR1α (protein kinase c-AMP-dependent regulatory type 1 α)

Psammomatous schwannomas, thyroid disease, multiple lentigines, blue nevi, testicular tumors, cutaneous and cardiac myxomas

Chédiak-Higashi Syndrome

AR

LYST1 (lysosomal transport)

Oculocutaneous albinism, ataxia, giant lysosomal granules, muscle weakness

CHILD syndrome (Congenital Hemidysplasia with Ichthyosiform Erythroderma and Limb Defects)

XLD

NSDHL gene mutation

Unilateral ichthyosiform erythroderma, limb/visceral hypoplasia, stippled epiphyses

Chondrodysplasia Punctata

XLR

Arylsulfatase E

Ichthyosis, sparse hair, stippled epiphyses (punctate chondral calcifications)

Chondrodysplasia Punctata, Rhizomelic

AR

PEX7 (peroxisomal biogenesis disorder)

Stippled epiphyses, accumulation of phytanic acid, follicular atrophoderma, scarring alopecia, cataracts, rhizomelia (striking shortening of proximal limbs)

Chondrodysplasia Punctate, XLD (Conradi-Hünermann-Happle Syndrome)

XLD

EBP (emopamil-binding protein)

Ichthyosiform erythroderma (along lines of Blaschko), follicular atrophoderma, patchy alopecia, cataracts, stippled epiphyses

Chronic Granulomatous Disease

XLR (mostly)

CYBB (cytochrome B, b subunit phagocyte NADPH oxidase defect, so unable to deliver respiratory burst for catalase-positive bacteria)

Recurrent infections, initially with staph infections around ears/nose, lymphadenopathy, cutaneous abscesses, suppurative lymphadenitis

Citrullinemia

AD

ASS (arginosuccinate synthetase, in urea cycle)

Lethargy, poor feeding, seizures, vomiting

Cockayne Syndrome

AR

ERCC8 (CSA)

ERCC6 (CSB)

Premature aging, cataracts, cachectic dwarfism, retinitis pigmentosa, photosensitivity

Congenital Contractural Arachnodactyly

AD

FBN2 (fibrillin-2)

Crumpled ears, arachnodactyly, long limbs, scoliosis

Congenital Ichthyosiform Erythroderma (Nonbullous CIE)

AR

TGM1 (transglutaminase-1)

ALOX12B (lipoxygenase)

ALOXE3 (lipoxygenase)

Collodion membrane, generalized erythroderma with fine scaling (flexural involvement), palmoplantar keratoderma (PPK)

Cowden Syndrome (Multiple Hamartoma Syndrome)

AD

PTEN (tumor suppressor gene)

Trichilemmomas, oral papillomas, ↑ CA (breast, thyroid follicular, colon), fibrocystic breast changes, cobblestoning of mucosa

Cutis Laxa

AR

FBLN5 (fibulin 5)

Loose pendulous skin with decreased elasticity, diverticulae (bladder/GI), pulmonary emphysema, pulmonary artery stenosis

Cutis Laxa

AD

ELN (elastin), FBLN5

Loose pendulous skin, systemic involvement uncommon

Cutis Laxa (Occipital Horn Syndrome, EDS IX)

XLR

ATP7A (copper transport disease)

Mild skin laxity, skeletal malformations, GU tract abnormalities, joint laxity

Darier Disease (Darier-White Disease) (Keratosis Follicularis)

AD

SERCA2 (calcium-dependent ATPase 2A2)

Acrokeratosis verruciformis, warty papules/plaques in seborrheic distribution, red/white longitudinal streaking of nails with v-shaped nicks at free margin

Dyskeratosis Congenita (Zinsser-Engman-Cole Syndrome)

XLR

AD

DKC1 (dyskerin: ribosome assembly chaperone)

TERC (telomerase RNA component)

Reticulate gray brown hyperpigmentation, dystrophic nails, alopecia, premalignant leukoplakia, pancytopenia, continuous lacrimation, malignancy

EB Recessive Dystrophic (RDEB-HS) (Hallopeau-Siemens)

AR

Type VII collagen (premature termination codon)

Severe widespread bullae at birth, scarring on hands/feet (mitten deformity), nail dystrophy, mucosal strictures, oral/esophageal/skin SCCs

EB, Dominant Dystrophic (DDEB) (Cockayne-Touraine)

AD

Type VII collagen (anchoring fibrils)

Bullae mainly over extremities, nail dystrophy, less severe than RDEB

EB Simplex (Dowling-Meara)

AD

K5/14 (EM: clumped tonofilaments in basal layer)

Herpetiform bullae, early death, PPK, nail dystrophy, mucosal involvement (laryngeal, esophageal)

EB Simplex (EBS) (Weber-Cockayne) (Localized)

AD

K5/14 (keratin)

Onset in childhood, bullae mainly in extremities (hands, feet), heals without scarring

EBS with Muscular Dystrophy

AR

Plectin (hemidesmosome)

Muscular (myotonic) dystrophy, widespread bullae at birth, scarring, early death

EB Junctional (JEB) (Herlitz) (EB Lethalis)

Split at lamina lucida

AR

LAMA3 (subunit of laminin 5, now called laminin 332 ) (premature termination codon)

Widespread bullae, exuberant perioral granulation tissue, early death, enamel defects, severe mucosal involvement (respiratory/GI tract), ± hoarseness

EB Junctional (Non-Herlitz) (Generalized Atrophic Benign EB)

AR

Laminin 332 (5) or BPAG2

Bullae, mild oral involvement, scarring alopecia, improves over time

EB Junctional with Pyloric Atresia

AR

α6β4 (integrin)

Bullae, pyloric atresia, hydronephrosis, mucosal erosions

Ectodermal Dysplasia with Skin Fragility

AD

Plakophilin 1 and 2 (mainly)

Fragile bullae and erosions/crust, perioral fissuring and cheilitis, PPK, nail dystrophy

EEC Syndrome (Ectrodactyly, Ectodermal Dysplasia, Cleft Lip/Palate)

AD

p63 gene

Cleft lip/palate, ectodermal dysplasia, ectrodactyly (absence of one or more central digits of hand or foot, also called ‘lobster claw deformity’)

Epidermodysplasia Verruciformis

AR

EVER1, EVER2

Abnormal susceptibility to human papillomaviruses of the skin (often HPV 5/8/47), SCCs

Epidermolytic Hyperkeratosis (Generalized EHK) (Bullous CIE)

AD

K1, K10 (clumping of keratin filaments in suprabasal layers)

Erythema/blistering in infancy and replaced by hyperkeratosis (flexural predominance)

Erythrokeratoderma Variabilis (Mendes da Costa)

AD (mainly)

GJB3 and GJB4 (connexin 31 and 30.3)

Transient erythematous figurate patches, fixed hyperkeratotic plaques

Fabry Disease (Angiokeratoma Corporis Diffusum)

XLR

α-Galactosidase A

Angiokeratomas, pain/paresthesia of limbs, whorled corneal opacities, hypohidrosis, renal and coronary insufficiency, ‘maltese crosses’ (birefringent lipids in urine)

Familail Mediterranean Fever (FMF)

AR

MEFV (pyrin, also known as marenostrin)

Recurrent febrile episodes with self-limited but painful episodes of synovitis, peritonitis, pleuritis

Familial Partial Lipodystrophy (FPLD)

AD

LMNA (lamins A and C)

Absence of subcutaneous fat, muscular appearing arms/legs, acanthosis nigricans, diabetes mellitus

Focal Dermal Hypoplasia (Goltz Syndrome)

XLD

POCRN (X chromosome: encodes acyltransferase)

Alopecia, fat herniation, osteopathia striata, mucocutaneous papillomas and pits

Gardner Syndrome (Familial Polyposis of the Colon)

AD

APC (adenomatosis polyposis coli)

GI polyps, ↑ colon cancer, osteomas (jaw), supernumerary teeth, epidermoid cysts, CHRPE (congenital hypertrophy retinal pigment epithelium)

Gaucher Disease

AR

β-Glucosidase (also known as glucocerebrosidase)

Erlenmeyer flask bone deformity, bone pain, aseptic necrosis, hepatosplenomegaly, ± CNS involvement

Gorlin Syndrome (Nevoid BCC Syndrome) (Basal Cell Nevus Syndrome)

AD

PTCH (patched mutation → SMO activation [Hedgehog pathway] resulting in ↑ Gli)

Palmoplantar pits, jaw cysts, bifid ribs, ovarian fibromas, medulloblastomas, falx calcification

Griscelli Syndrome

AR

Rab 27 A

MyO5A (myosin V)

Pancytopenia, immunodeficiency, silvery gray hair, partial albinism, ↑ infections, neurological impairment

Hailey-Hailey Disease (Familial Benign Chronic Pemphigus)

AD

ATP2C1 (golgi-associated Ca2+ ATPase, interferes with intracellular calcium signaling)

Flaccid blisters and erosions in intertriginous areas with vegetating plaques

Haim-Munk Syndrome

AR

Cathepsin C

Erythematous PPK, onychogryphosis, periodontitis, early loss of teeth, acro-osteolysis

Harlequin Fetus

AR

ABCA12

Restrictive plate-like scales, eclabion, death due to respiratory difficulty and/or sepsis

Hartnup Disease

AR

SLC6A19 (defective intestinal/renal neutral amino acid transport)

Pellagra-like dermatosis with photosensitivity, ataxia, tremors

Hereditary Angioedema

AD

SERPING1 (gene for C1-INH, serine protease inhibitor)

Episodes of nonpitting swelling (angioedema), ± abdominal pain, diarrhea, paroxysmal colicky pain

Hereditary Congenital Lymphedema (Nonne-Milroy)

AD

VEGFR3 (FLT4)

Congenital lymphedema, chylous ascites, bilateral pleural effusions

Hereditary Hemorrhagic Telangiectasia (Osler-Weber- Rendu)

AD

ENG (endoglin)

ACVRL1 (ALK1)

Pulmonary and hepatic AVMs, recurrent epistaxis, visceral hemorrhages (especially GI), telangiectasias

Hermansky-Pudlak syndrome (HPS)

AR

HPS (lysosomal transport protein)

Oculocutaneous albinism, no dense bodies in platelets, ↑ bleeding, granulomatous colitis, pulmonary fibrosis

Hidrotic Ectodermal Dysplasia

(Clouston Syndrome)

AD

GJB6 (connexin 30: gap junction protein)

PPK, nail dystrophy, sparse hair, patchy alopecia, normal teeth, normal sweating, tufting of the terminal phalanges

Holocarboxylase Synthetase Deficiency
 
HLCS (holocarboxylase synthetase)

Alopecia, perioral and perianal scaly dermatitis, lethargy, difficulty feeding

Homocystinuria

AR

CBS (cystathione β-synthetase)

Marfanoid habitus, downward displaced lens (ectopia lentis), thromboembolic events, neurologic features

Howel-Evans Syndrome (Tylosis-Esophageal Carcinoma)

AD

TOC (envoplakin)

Focal PPK over pressure areas (balls of feet > hands), oral leukokeratosis, ↑ esophageal carcinoma

Hunter Syndrome

XLR

Iduronate-2-sulfatase

Ivory-colored papules between scapula, cardiac involvment, joint stiffness, mental retardation

Hurler Syndrome

AR

α-L-iduronidase

No skin findings

Hyper-IgE Syndrome (Job Syndrome)

AD (mainly)

STAT3

Recurrent ‘cold’ staph infections, eczema, retained primary teeth, ↑ eosinophils, ↑ IgE

Hypohidrotic Ectodermal Dysplasia (HED) (Anhidrotic Ectodermal Dysplasia) (Christ-Siemens-Touraine)

XR

EDA (ectodysplasin A)

EDAR (EDA receptor)

NF-κB critical role

Hypotrichosis, ↓↓ sweating with heat intolerance, periorbital hyperpigmentation, peg-shaped teeth, anodontia, normal nails, saddle facies with large lips

ADAR

Hypohidrotic ED with Immunodeficiency (HED-ID)

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Aug 7, 2017 | Posted by in Dermatology | Comments Off on High Yield Facts and Buzz Words
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