Naxos disease, also known as keratoderma with woolly hair type 1, is a rare genetically inherited syndrome characterized by the triad of arrhythmogenic right ventricular dysplasia / cardiomyopathy (ARVD/C), woolly hair, and diffuse nonepidermolytic palmoplantar keratoderma (PPK).
Naxos disease is caused by a mutation of the JUP gene on chromosome 17. This gene encodes for the plakoglobin protein and is inherited in an autosomal recessive manner. Plakoglobin is a component of desmosomes and adherens junctions; abnormal protein will lead to abnormal myocardial gap junction remodeling, abnormal mechanical cardiac contraction, increased hair follicle proliferation, and hyperkeratosis induced by mechanical pressure.
The disease has a frequency of 1:1000 in the population of the Greek islands. Sporadic cases have also been identified in Israel, Saudi Arabia, Turkey, Bangladesh, and Canada. Consanguinity is the most significant risk factor for the development of disease.
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, but striate keratoderma is occasionally seen. Patients may begin to experience palpitations or syncope in adolescence. Severe complications, including fatal ventricular tachyarrhythmias, heart failure, and sudden cardiac death may occur.
Naxos disease
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Synopsis
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:
715535009 – Keratosis palmoplantaris and arrhythmogenic cardiomyopathy syndrome
I42.8 – Other cardiomyopathies
Q82.8 – Other specified congenital malformations of skin
Q87.89 – Other specified congenital malformation syndromes, not elsewhere classified
SNOMEDCT:
715535009 – Keratosis palmoplantaris and arrhythmogenic cardiomyopathy syndrome
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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 (TN)
- Keratoderma with woolly hair type 2 (Carvajal syndrome) – nontransgrediens, woolly hair, and dilated left ventricular cardiomyopathy
- Keratoderma with woolly hair type 3 – nontransgrediens, milder extracardiac symptoms than type 1
- Keratoderma with woolly hair type 4 – nontransgrediens, woolly or sparse hair, irregularly curved fingernails and toenails, no cardiac involvement
- Vorner type PPK – nontransgrediens, no associated abnormalities, epidermolysis on biopsy
- Unna-Thost type 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
- 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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Last Reviewed:03/27/2022
Last Updated:04/26/2022
Last Updated:04/26/2022