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SynopsisHowel-Evans syndrome, also known as Clarke-Howel-Evans-McConnell syndrome, is a rare genetic disorder characterized by nonepidermolytic palmoplantar keratoderma (NEPPK), oral leukoplakia, and an increased risk of squamous cell carcinoma of the esophagus. This very rare syndrome is inherited in an autosomal dominant fashion and is secondary to mutations of the rhomboid 5 homolog 2 (RHBDF2) gene. Howel-Evans syndrome has been detected only in patients of Western European descent and in American families of similar ancestry, suggesting this condition is either exceedingly rare or has not yet been reported in other populations.
Patients present with tylotic changes (a thickening of the skin, or callus formation) of the palms and soles, typically over areas of pressure, in early youth. The hyperkeratotic changes may be confluent over the palms and soles or localized to the areas of pressure, such as the heels and forefeet. Painful fissures are a common complication. In general, the feet tend to be more severely affected, most likely because of increased mechanical pressure in this area. The hyperkeratosis does not extend to the dorsum of the acral areas.
There have been a number of cases of Howel-Evans syndrome with associated ectodermal abnormalities. These findings suggest that this syndrome may be a variant of ectodermal dysplasia.
Q82.8 – Other specified congenital malformations of skin
111030006 – Howel-Evans syndrome
Differential Diagnosis & Pitfalls
- Mucosal hyperkeratosis syndrome – Autosomal dominant (AD) inheritance; look for white lesions of the gingiva and PPK.
- Focal PPK with oral mucosa hyperkeratosis – Look for focal PPK, oral hyperkeratosis, subungual hyperkeratosis (mutation in keratin 16).
- Pachyonychia congenita type 1 (Jadassohn-Lewandowsky syndrome) – AD inheritance; congenital pachyonychia, hyperhidrosis of the palms and soles, follicular keratosis, palmoplantar keratoderma, and leukoplakia of oral and anal mucosa.
- Acrokeratosis neoplastica (Bazex syndrome)
- Acanthosis nigricans maligna
- Tripe palms
- Other keratodermas