Hidrotic Ectodermal Dysplasia 2

Clinical characteristics: Hidrotic ectodermal dysplasia 2, or Clouston syndrome (referred to as HED2 throughout this GeneReview) is characterized by a triad of major clinical features including partial-to-complete alopecia, nail dystrophy, and palmoplantar hyperkeratosis. Sweating is preserved and there are usually no dental anomalies.

Sparse scalp hair and dysplastic nails are seen early in life. In infancy, scalp hair is fine, sparse, and brittle. Progressive hair loss may lead to total alopecia by puberty. The nails may be milky white in early childhood; they gradually become dystrophic, thick, and distally separated from the nail bed. Palmoplantar keratoderma may develop during childhood and increases in severity with age. Associated features may include cutaneous hyperpigmentation (particularly over the joints) and finger clubbing. The clinical manifestations are highly variable even within the same family.

Diagnosis/testing: The diagnosis of HED2 is established in a proband with suggestive findings and a heterozygous pathogenic variant in GJB6 identified by molecular genetic testing. Targeted analysis for the four most common GJB6 pathogenic variants detects pathogenic variants in approximately 100% of affected individuals.

Management: Treatment of manifestations: Special hair care products to help manage dry and sparse hair; wigs; artificial nails; emollients and keratolytics to relieve palmoplantar hyperkeratosis.

Genetic counseling: HED2 is inherited in an autosomal dominant manner. Most individuals with HED2 have an affected parent; de novo pathogenic variants have also been reported. Offspring of affected individuals have a 50% chance of inheriting the pathogenic variant and being affected. Once the causative GJB6 pathogenic variant has been identified in an affected family member, prenatal testing for a pregnancy at increased risk and preimplantation genetic testing for HED2 are possible.