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Keratoderma with woolly hair type III
Other Resources UpToDate PubMed

Keratoderma with woolly hair type III

Contributors: Jourdan Brandon, Susan Burgin MD
Other Resources UpToDate PubMed

Synopsis

Keratoderma with woolly hair type 3 is a genetically inherited syndrome characterized by arrhythmogenic right- or biventricular dysplasia with or without woolly hair and diffuse nonepidermolytic palmoplantar keratoderma (PPK). It is exceedingly rare, with only a handful of documented cases in Germany, Lebanon, Pakistan, Italy, and the Alberta Hutterite population.

Keratoderma with woolly hair type 3 is caused by a mutation in the DSC2 gene on chromosome 18, which encodes for desmocollin 2. Desmocollin 2 is a cadherin that plays an essential role in the function of desmosomes found in epithelial cells, cardiomyocytes, and other specialized cell types. Dysfunction results in progressive fibrofatty replacement of the myocardium, increased hair follicle proliferation, and hyperkeratosis induced by mechanical pressure. The DSC2 mutation is inherited in an autosomal dominant manner, but an autosomal recessive inheritance pattern has also been noted in association with the cardiocutaneous phenotype. Desmocollin 2 is one of three isoforms of desmocollin (desmocollin 1, desmocollin 2, and desmocollin 3), but is the only one that is present in cardiac tissue. Compensation by desmocollin 1 and desmocollin 3 in noncardiac tissue results in the mild or absent presentation of cutaneous and hair involvement.

Woolly hair presents as tightly coiled, unusually frizzy, difficult-to-comb hair diffusely on the scalp that is apparent at birth. Palmoplantar hyperkeratosis begins in the first year of life. The keratoderma is usually diffuse and nontransgrediens. The age at which cardiac symptoms appear is variable but can emerge as early as adolescence. Cardiac presentation can range from asymptomatic to mild symptoms (ie, palpitations, syncope) to severe complications (ie, fatal ventricular tachyarrhythmias, heart failure, sudden cardiac death). Arrhythmogenic cardiomyopathy in most reported cases of keratoderma with woolly hair type 3 is limited to the right ventricle. Biventricular involvement can occur but is not seen in all cases. Isolated left ventricular arrhythmogenic cardiomyopathy has not been linked to the DSC2 mutation.

Codes

ICD10CM:
I42.8 – Other cardiomyopathies
Q82.8 – Other specified congenital malformations of skin
Q87.89 – Other specified congenital malformation syndromes, not elsewhere classified

SNOMEDCT:
254231002 – Congenital wooly hair
400123002 – Hereditary diffuse palmoplantar keratoderma

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Diagnostic Pearls

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Differential Diagnosis & Pitfalls

Diffuse woolly hair:
  • Skin fragility-woolly hair syndrome (SFWHS) – an autosomal recessive disease characterized by focal and diffuse PPK, woolly hair, recurrent bullae, and nail dystrophy, without the presence of cardiomyopathy
  • Trichohepatoenteric syndrome – diffuse woolly hair on the scalp, trichorrhexis nodosa, failure to thrive, infantile diarrhea, and liver disease
  • Hereditary woolly hair – no additional clinical features present
  • Uncombable hair syndrome
  • Pili torti
  • Trichorrhexis nodosa
Inherited diffuse PPK with woolly hair:
  • Keratoderma with woolly hair type 1 (Naxos Disease) – nontransgrediens, woolly hair, ARVD/C; extracardiac manifestations more prominent than type 3; use genetic testing to differentiate
  • Keratoderma with woolly hair type 2 (Carvajal syndrome) – nontransgrediens, woolly hair, and dilated left ventricular cardiomyopathy
  • Keratoderma with woolly hair type 4 – nontransgrediens, woolly or sparse hair, irregularly curved fingernails and toenails, no cardiac involvement
Other inherited diffuse PPKs:
  • Vörner type PPK – nontransgrediens, no associated abnormalities, epidermolysis on biopsy
  • Unna-Thost PPK – nontransgrediens, no associated abnormalities (epidermolytic)
  • Nagashima-type PPK – transgrediens, mild, nonprogressive PPK with white, spongy, hyperkeratotic lesions over the knees, elbows, and Achilles tendon area; common in Asia
  • Greither PPK – transgrediens, presents at infancy with transient blistering that progresses to hyperkeratotic lesions over the flexures, elbows, knees, and Achilles tendon area
  • Sybert syndrome – transgrediens, hyperkeratotic lesions over elbows and knees, erythema in the perioral and periorbital regions
  • Bart-Pumphrey syndrome – nontransgrediens, leukonychia, sensorineural deafness, knuckle pads
  • Keratitis ichthyosis deafness (KID) syndrome – nontransgrediens, acrofacial hyperkeratosis, ichthyosis, sensorineural deafness
  • Howel-Evans syndrome – nontransgrediens, tooth loss, oral leukoplakia, esophageal carcinoma development
  • Vohwinkel syndrome – transgrediens, starfish-shaped keratoses over knuckles, deafness

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References

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Last Reviewed:03/27/2022
Last Updated:04/26/2022
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Keratoderma with woolly hair type III
A medical illustration showing key findings of Keratoderma with woolly hair type III (Hair)
Copyright © 2023 VisualDx®. All rights reserved.