Genoderm and Peds Derm Flashcards
Hyper-IgE syndrome is associated with which mutations (3)? What differentiates the clinical presentation of these 3 mutations?
STAT3, DOCK8, Tyk2
- All have eczema, sinopulm infections, elevated IgE
- STAT3 = Job Syndrome; AD with connective tissue, skeletal and vascular abnormalities
- DOCK8: severe cutaneous viral infections (e.g. warts) and premature malignancies
- Tyk2: nontuberculous mycobacterial infections
Hidrotic Ectodermal Dysplasia
Eponym?
Gene?
Features?
Cloustons Syndrome connexin 30 (gjb6)
Hypotrichosis, nail dystrophy, diffuse PPK, MR
normal teeth and sweating
What genodermatoses are associated with a connexin 26 mutation (4)?
- KID syndrome
- PPK with deafness
- Volwinkel syndrome
- Bart-Pumphrey
Type of EB characterized by herpitiform blisters at birth?
EBS, generalized, severe (Dowling-Mera)
What is mutated in a child with wooly hair, PPK and right sided cardiomyopathy?
plakoglobin = Naxos Syndrome
desmoplakin = Carvajal Syndrome with PPK, Wooly hair and LEFT sided Cardiomyopathy.
Remember: p points to the Right; d points to the left.
What are the different clinical features of Ehlers Danlos when the following are mutated: Tenascin X, lysyl hydroxylase (PLOD), type III collagen, type V collagen, pro collagen N-proteinase (ADAMTS2), type I collagen?
- Tenascin-X = Hypermobility: joint hyper mobility, minimal skin findings; can have congenital adrenal hyperplasia
- Lysyl hydroxylase = Kyphoscloliosis: respiratory issues, muscle weakness, ocular fragility
- Type III collagen = Vascular: visible veins, vascular fragility, bruising, hypermobility
- Type V collagen = Classic: hyperextensible skin/joints, fish-mouth scars, Gorlin sign (tongue to nose), no frenulum, MVP
- Pro-collagen N-proteinase = Dermatosparaxis: extremely fragile, sagging skin; hernias, easy bruising
- Type 1 collagen = Arthrochalasia: joint hypermobility, dislocation of large joints (congenital hip dislocations), scoliosis, easy bruising
What genodermatosis is associated with a mutation in LEMD3? Function of LEMD3? Clinical manifestations?
Buschke-Ollendorf syndrome (AD)
LEMD3 encodes a inner nuclear membrane protein
- Elastomas (Dermatofibrosis lenticularis disseminata)
- Osteopoikilosis (bushes in the bone!)
What mutation is present in DSAP and Hyper IgD Syndrome?
Mevalonate kinase gene (MVK) - may regulate calcium-induced keratinocyte differentiation and may protect from UVA-induced apoptosis
Which genodermatoses have trichoepitheliopmas (3)?
Brook-Spiegler, Rombo, Bazex
Differential diagnosis of trichorrhexis nodosa?
“TACK + others” = Trichothiodystrophy and Traumatic hair care; Arginosuccinic aciduria, Citrullinemia (arginocyccinate synthetase defect), Kinky Hair (Menke’s); others = Nethertons, metabolic disorders including zinc and biotinidase deficiency
What conditions have defective DNA Helicases (3)?
Bloom (RecQL2), Rothmund-Thompson (RecQL4), Werner(adult progeria - WRN gene)
What is the differential diagnosis of atrophoderma vermiculatum (honeycomb pattern of atrophic scars on face)?
- Tuzun syndrome (+ scrotal tongue)
- Rombo (+ BCC, milia, peripheral vasodilation with cyanosis, trichoeps)
- Nicolau-Balus (+ eruptive syringomas, milia)
- Braun-Falco-Marghescu (+ KP, palmoplantar hyperkeratosis)
- Down syndrome
What is the mutation and features of EEC syndrome?
EEC = Ectrodactyly (lobster claw deformity) - Ectodermal Dysplasia - Cleft lip/palate
mutation in EEC1, EEC2 or EEC3 - all are P63 (tumor suppressor needed for limb, craniofacial and epidermal morphogenesis).
50% also have sensorineural deafness; 30% have hydronephrosis; can have blond, sparse hair; 70% cleft lip/palate, hypodontia
What is the mutation and features of AEC syndrome? Eponym?
AEC = Ankyloblepharon (fusion of eyelids with strands of skin) - Ectodermal Dysplasia - Cleft palate
Eponym = Hay-Wells
AD mutation of p63 gene (hererozygous missense mutation in SAM domain).
Erosive scalp dermatitis; sparse hair +/- scarring alopecia; dystrophic/absent nails; lacrimal duct atresia; chronic otitis media that can lead to deafness; can have collodion membrane-like presentation at birth; 80% cleft lip/palate
Elastosis Perforans Serpiginosa is associated with which conditions (10)?
“MAD PORES” = Marfans, Morphea; Acrogeria; Down Syndrome; Pseudoxanthoma Elasticum; Osteogenesis Imperfecta; Rothmund-Thompson; Ehlers Danlos; Scleroderma and Cutis Laxa
Name the gene mutation and protein affected in the 4 types of oculocutaneous albinism
OCA1 = TYR (tyrosinase) OCA2 = OCA2 (P gene; also affected in Angelman and Prader-Willi) OCA3 = TYRP1 (transport-related protein 1) OCA4 = MATP (membrane associated transport protein)
What is the juvenile counterpart to DFSP? What are key histopathologic findings?
Giant Cell Fibroblastoma; multinucleated giant cells lining vascular like spaces
Which PPKs have periodontitis as a features?
Papillon-Lefevre and Haim-Munk (AR; Cathepsin C mutations in both, which is a lysosomal protease
Haim-Monk is Papillon-Lefevre + onychogryphosis
Name 3 causes of transient neonatal pustules. What would smear show (neuts or eos)? Who gets each? Treatment?
- Transient Neonatal Pustular Melanosis: present at birth as pustules or “collarettes of scale” in pigmented individuals; smear shows NEUTS. No Tx necessary.
- Erythema Toxicum Neonatorum: 24-48 h after birth; 50% of term babies; rare in preeemies. Smear shows EOS. No Tx - resolves in a couple weeks.
- Neonatal Cephalic Pustulosis (Neonatal Acne): onset first 30 days; due to Malassezia; smear shows NEUTS and yeast.
Name 3 conditions associated with asplasia cutis congenita.
- Bart Syndrome: ACC of lower extremity + dominant dystrophic epidermolysis bullosa
- Adams-Oliver Syndrome: ACC of scalp with skull ossification defect + extensive CMTC + limb defects + cardiac anomalies
- Seitles Syndrome: bilateral temporal ACC + abnormal eyelashes, upslanting eyebrows + leonine facies
What are the diagnostic criteria for Kawasaki disease (need 5 of 6)?
- Rash
- Fever x 5 days
- Conjunctivitis (with perilimbic sparing)
- Palmoplantar erythema, edema or desquamation
- Swollen lips or red tongue
- Cervical lymphadenopathy (>/= 1.5 cm)
Describe the 3 forms of childhood PRP - clinical features, likelihood of resolution.
- Classic Juvenile (III): Resembles classic adult; onset first 2 years of life, resolves within 3 years
- Circumscribed Juvenile (IV): extensor surfaces involved, onset in prepubertal years; 50% persist into adulthood (most common childhood form)
- Atypical Juvenile (V): type III + sclerodermoid changes of hands/feet; familial. Presents in childhood and persists.
Which innate antimicrobial peptides are deficient in atopic dermatits?
human beta-defencins (HBD)
Canthelicidins (LL37)
Name 5 genoderms with lentigines. Mutations? Other features?
- LEOPARD = PTPN11 gene (AD); Lentigines, EKG changes, ocular hypertelorism, pulm stenosis, abnormal genitalia, growth retardation, deafness
- Carney complex (LAMB or NAME Syndrome) = PRKAR1A (AD); psammomatous melanotic schwannomas, cardiac/skin myxomas, blue nevi, endocrine overactivity (nodular adrenocortical disease –> Cushings; pituitary GH-secreting tumors; testicular tumors)
- Peutz-Jeghers = STK11 (AD); mucocutaneous lentigines, intestinal polyposis, intussusception, malignancies (GI adenocarcinoma, other solid organs - breast, uterine, cervix, thyroid)
- Laugier-Hunziker Syndrome = mucocutaneous lentigines, longitudinal melanonychia, genital melanosis
- Bannayan-Riley-Ruvalcaba = PTEN (AD); penile > vulvar lentigines, lipomas, hemangiomas, trichilemmomas; risk of breast/thyroid/GI cancers
What are the size cutoffs for congenital nevi?
Small < 1.5 cm
Medium 1.5 - 20 cm
Large > 20 cm or 10% BSA
What is the most common genetic mutation in Spitz nevi?
Gain of 11p - HRAS gene
What features are common of all Junctional Epidermolysis Bullosa variants?
- Enamel Hypoplasia with pits/caries
- Anemia
- Growth retardation
- Recurrent tracheobronchial infections
Multiple pilomatricomas are associated with which conditions (5)?
- Myotonic dystrophic with beta-catenin defect
- Rubenstein-Taybi
- Turner
- Gardner
- Sarcoidosis
Which 3 adnexal neoplasms are seen in Brooke-Spiegler Syndrome? Mutation? Risk for malignancy?
- Trichoepitheliomas
- Cylindromas
- Spiradenomas
- Risk of salivary gland tumors
- Mutation in CYLD gene, which regulates NF-kB
What are the histopathologic findings of infantile digital fibromatosis? Stains?
- Interlacing fascicles of fibroblasts/myofibroblasts in collagenous stroma with eosinophilic inclusions
- Inclusions are red with trichrome, purple with PTAH
Name the 4 Langerhans Cell Histiocytoses and describe features.
- Letterer-Siwe: multisytem, onset before 2; skin findings in seborrheic distribution
- Hand-Schuller-Christian: triad of DI, osteolytic bone lesions, exophthalmos; onset 2-6; eval for systemic disease with CBC, LFTs, skeletal survey
- Eosinophilic Granuloma: localized to bone (cranium), spontaneous fractures; onset older children
- Congenital Self-Healing Reticulohistiocytosis (Hashimoto-Pritzker): limited to skin with onset around birth; widespread crusted papules that heal within weeks-months
What does PHACES stand for?
Posterior fossa malformation (Dandy Walker malformation most common) Hemangioma Arterial anomalies Cardiac defect, Coarctation Eye abnormalities Sternal defect, Supraumbilical raphe
What does LUMBAR stand for (should replace PELVIS because is more complete)?
Lower body hemangioma / Lipomas (lipomyelomeningocele)
Urogenital anomalies
Myelopathy
Bony deformities
Anorectal anomalies (imperforate anus, skin tags)/ Arterial anomalies
Renal anomalies
What does POEMS stand for? Other features?
Polyneuropathy Organomegaly Endocrinopathy Monoclonal gammopathy (or Castlemans) Skin lesions
- Pathognomonic skin lesion = glomeruloid hemangioma; can also have cherry and lobular angiomas
- Other features: sclerotic bone lesions, papilledema, pleural effusions, peripheral edema, ascites, > 90% have diffuse cutaneous hyperpigmentation
Name the X-linked Recessive Genoderms…
“CHAD’S Kinky WIFE, CHANDra”
Chronic Granulomatous Disease Hunter Disease Anhidrotic Ectodermal Dysplasia Dyskeratosis Congenita SCID
Menke’s Kinky Hair Disease
Wiskott-Aldrich Syndrome Ichthyosis, X-linked Fairy disease Ehlers-Danlos (type V and IX) Chondrodysplasia Punctata (NOT Conradi-Hunerman type) Hypohidrotic Ectodermal Dysplasia w/ Immunodef Agammaglobulinemia, Bruton's Lesch-Nyhan Syndrome
Name the X-linked Dominant Genoderms..
“BIG ChOMP”
Bazex Syndrome
Incontinentia Pigmenti (Bloch-Sulzberger)
Goltz syndrome
CHILD syndrome
Oro-Facial-Digital Syndrome
MIDAS syndrome (micrognathia, dermal aplasia, sclerocornea)
Chondrodysplasia Punctata (Conradi-Hunermann type)
Most types of Xeroderma Pigmentosum are due to defects encoding _________. XP Variant is due to a mutation in __________.
Nucleotide Excision Repair
XP Variant: DNA polymerase; no neuro abnormalities in XP variant
Which conditions have mutations in excision repair cross-complementation groups (ERCC)?
- Xeroderma pigmentosum
- Cockayne Syndrome (ERCC6 and ERCC8)
- Trichothiodystrophy or PIBIDS (ERCC2 and ERCC3)
All are AR!
