Disorders of the Hair/Nail/Ectodermal dysplasias Flashcards
What is the gene and mode of inheritance in pachyonychia congenita?
KRT6A, KRT6B, KRT16, KRT17
AD
What are the 3 primary characteristics of in pachyonychia congenita?
Onychodystrophy, plater keratoderma, and plantar pain
- These develop in childhood
What is the appearance of the onychodystrophy in pachyonychia congenita?
Discoloration and progressive hyperkeratosis of the nail plate and is most pronounced at the free edge giving it a pincer-like appearance
What are the acral skin findings in pachyonychia congenita?
Most severe on the palmar surfaces
Focal, painful, keratoderma and hyperhidrosis –> leads to secondary bullae and fissures (develop in childhood)
What are the two types of pachyonychia congenita?
Type I: Jadassohn-Lewandowski
Type II: Jackson-Lawler
What genes are involved in pachyonychia congenita type I?
These are the KRT6A and KRT16
What is the phenotype of pachyonychia congenita type I?
Full expression happens later, usually not until late childhood or adulthood
Recurrent paronychia
Get benign oral leukoplakia of the tongue and buccal mucosa
Follicular hyperkeratosis of knees, elbows, back, and buttocks
What is the phenotype of pachyonychia congenita type II?
Natal teeth
Steatocytomas
More mild keratoderma
What are the genes involved in pachyonychia congenita type II?
KRT6B and KRT17
What is the broad definition of the ectodermal dysplasias?
It is a heterogeneous group of genetic disorders that affect the hair/teeth/nails/eccrine glands to different degrees
What is the gene and inheritance of hypohidrotic ectodermal dysplasia?
Ectodysplasin (ED1) in classical cases (XLR)
Less commonly can have AD/AR mutations in ectodysplasin receptor (EDAR and ectodysplasin receptor-associated death domain (EDARDD)
Can female carriers of hypohidrotic ectodermal dysplasia have symptoms?
Yes, they get features that are segmental from random inactivation (alopecia, dental defects, and Blaschkoid linear patches of hypohidrosis
What is the clinical triad of hypohidrotic ectodermal dysplasia?
Decreased sweating, hypotrichosis, and abnormal dentition
What facial features can be seen in hypohidrotic ectodermal dysplasia?
Frontal bossing, large nostrils, wide/flat malar cheeks, thick everted lower lip, and prominent chin
What are the skin findings in hypohidrotic ectodermal dysplasia?
Thin, wrinkled, soft skin; darkening of the skin under the eyes
Mild onychodystrophy
Hair: can have hypotrichosis w/ thin, light hair; eyelashes absent
What are the teeth findings in hypohidrotic ectodermal dysplasia?
Delayed dentition, may have peg-shaped, conical or missing teeth
What are the systemic findings seen in hypohidrotic ectodermal dysplasia?
Risk of hyperthermia w/ the hypohidrosis, decreased lacrimation can be seen, can get sinus dz, pulmonary infections and asthma
What is the phenotype and cause of hypohidtrotic ectodermal dysplasia w/ immunodeficiency?
IKBKG/NEMO (XLR) or NFKBIA (AD)
These pts are susceptible to recurrent pyogenic and atypical mycobacterial infections
Board factoid
What is the involved gene and mode of inheritance of hidrotic ectodermal dysplasia?
Connexin 30 (GJB6)
AD
What is the clinical triad of hidrotic ectodermal dysplasia?
Marked onychodystrophy/chronic paronychia, palmoplantar keratoderma, and hair abnormalities
Important differences between the hypohidrotic and hidrotic ectodermal dysplasias?
In the hidrotic ectodermal dysplasia:
- Marked onychodystrophy, also marked hypotrichosis w/ thin brittle hair
- Normal sweating, facial features, and teeth
- Ophthalmologic and MSK sequelae: tufted distal phalanges, conjunctivitis, strabismus and cataracts
What is the gene involved in ectodermal dysplasia due to p63 mutation and what is the inheritance pattern?
P63, AD
What is p63 important for?
Critical transcription factor for ectodermal, orofacial, and limb development
How many defined clinical ectodermal dysplasia syndromes arising from p63 are there and what are they?
There are 4
- Rapp-Hodgkin syndrome
- Ankyloblepharon-ectodermal dysplasia-clefting syndrome (AEC)
- Ectodactyly ectodermal dysplasia-cleft lip/palate syndrome
- acro-dermato-ungual lacrimal-toot/limb-mammary syndrome, split hand-foot malformation
All of these have wiry/sparse hair, dystrophic nails, decreased number of teeth/hypoplastic enamel, hypohidrosis, decreased number of teeth/hypoplastic enamal, hypohidrosis, short stature, and poor weight gain
What is the Rapp-Hodgkin syndrome?
P63 ectodermal dysplasia, leads to clefting of lip/palate/uvula, hypoplasia of maxilla, small narrow nails, and small conical teeth
What is ankyloblepharon-ectodermal dysplasia-clefting syndrome?
Congenital fusion of eyelids (ankyloblepharon) and is a/w/ facial clefting or mid-face hypoplasia; diffuse collodion-like peeling/erythema seen at birth
- The scalp can have chronic erosive dermatitis –> can get frequent staph infections
What is the ectrodactyly ectodermal dysplasia-cleft lip/palate syndrome?
Ectrodactyly (developmental anomaly of a median ray of feet > hands which leads to “lobster claw” anomaly (missing digits/deformity of extremities), facial clefting, mild PPK, conductive hearing loss, and genitourinary anomalies
What is the gene and mode of inheritance in Rubinstein-Taybi syndrome?
CREBBP
Sporadic
What is the clinical phenotype in Rubinstein-Taybi syndrome?
Broad thumbs/halluces w/ racquet nails (brachyonychia)
- Capillary malformations, short, severe mental retardation, cryptorchidism, congenital heart defects, and typical facies (beaked nose, down slanting palpebral fissures, low-set ears, epicanthal folds, and grimacing smile), multiple pilomatrixoma
What is atrichia w/ papules?
Mutations in the hairless gene (HR)
- Hair normal at birth –> shed then doesn’t come back and you get milia-like papules that appear later
- can be a/w Vitamin-D resistant rickets
- Basically causes disintegration of the lower 2/3 of hair follicle
What are the two wooly hair genoderms?
Naxos: right ventricular cardiomyopathy, wooly hair
Carvajal: right ventricular cardiomyopathy, wooly hair
What is the underlying defect/issue with uncombable hair?
Pili trianguli et canalculi (so on EM cross section the hair looks triangular and there is a longitudinal depression
- Looks like shiny, “spun-glass” look
What is monilethrix?
There are uniform elliptical nodules along the hair shaft
- Hair normal at birth then in infancy it becomes brittle, short and has a beaded appearance
- A/w keratosis pilaris
- KRT81, KRT83, and KRT86 (AD) and desmoglein 4 (AR)
What is the appearance of pili torti?
Flattened, twisted hair shafts occuring at irregular intervals
What syndromes are a/w pili torti?
Menkes kinky hair syndrome, Bazex-Dupre-Christol syndrome, Rombo syndrome, Bjornstad syndrome, crandal syndrome
What is the appearance of trichorrhexis nodosa?
Light microscopy: nodules w/ the appearance of broom bristles
What are the most commonly associated genetic conditions w/ trichorrhexis nodosa?
Arginosuccinic aciduria, citrullinemia, oculo-dental-digital dysplasia, trichothiodystrophy, Netherton syndrome
What is the appearance of the trichorrhexis invaginata?
This has a ball in socket appearance, the end can look like a “golf tee”
What disease is trichorexis invaginata a marker for?
Netherton syndrome
What is Marie Unna hypotrichosis?
AD mutations in U2HR
Absence of scalp hair, eyebrows, and eyelashes at birth
Hair growth when it comes is coarse and twisted
What is the pathogenesis of loose anagen syndrome?
Can AD but usually sporadic mutation leading to defective inner root sheath keratinization so that the anagen hairs can be easily and painlessly plucked
What is the clinical phenotype in loose anagen syndrome?
Diffuse hair thinning, Hair can look fine, limp, and matted
On trichoscopy there are multiple anagen hairs (hockey sticks) that have a ruffled cuticles
What is Cornelia de Lange syndrome?
AD (mutation in NIPBL)
Hirsutism, synophrys, trichomegaly, low hairline, mental/psychomotor retardation, short stature, simian crease, cryptorchidism, hypospadias, renal issues, heart defects, lung infections
- Can lead to death or hearing loss
What is Ambras syndrome?
Excessive vellus-like hairs on the face, ears, and shoulders
What is keratosis Polaris atrophicans, ulerthema ophyrogenes subtype?
Erythematous papules w/ follicular plugging and atrophic scarring
- You get scarring alopecia of the eyebrows (especially lateral part)
