DISEASE CARD

Disease group Ectodermal Dysplasia
DISEASE NAME CLOUSTON SYNDROME
Synonymous Hidrotic ectodermal dysplasia
Estimated prevalence -
OMIM 129500
Inheritance Autosomal Dominant
Gene (s) GJB6 (604418)

Defintion

Hidrotic ectodermal dysplasia is a rare autosomal dominant ectodermal dysplasia disorder first described by Clouston in 1929.1 Characteristic clinical features include nail dystrophy, sparse hair or total alopecia, skin hyperpigmentation (especially over joints) and occasionally palmar hyperkeratosis.

Clinical Description

In contrast to X-linked HED (hypohidrotic ectodermal dysplasia), patients have normal sweating and no teeth abnormalities. However, other ectodermal structures may be affected: nails are slow growing, hypoplastic or dystrophic (may become worse over time). Scalp and body hair is hypochromic, fine, slow-growing and sparse. Ultrastructurally, it may be abnormally shaped, twisted, small, or square in cross‐section. Total alopecia is common. The skin is commonly dry and localized hyperpigmented (e.g. over knuckles, elbows, axillae, bony prominences). Diffuse or stippled palmar and plantar hyperkeratosis with reduced keratinocyte desquamation that rarely extends onto the dorsum of the hands and feet, occurs frequently and can be severe. There are reports of cutaneous malignancies (squamous cell carcinoma, melanoma) arising from the nail bed and palmar tissue. Eye pathologies include conjunctivitis, strabismus and congenital cataract. Further features include tufting of the terminal phalanges, oral leucoplakia, sensorineural hearing loss and thickened skull bones.2-4

Pathogenesis

Lamartine et al. (2000) identified mutations in the GJB6 gene (locus 13q12) which encodes connexin-30 as the molecular basis of Clouston syndrome.5 Connexins are involved in the formation of gap junctions which are intercellular channels connecting the cytoplasm of adjacent cells.

Diagnosis

The condition is present from birth, however, milder cases may not be diagnosed until a child gets older and nails or hair fail to develop normally.

Treatment

The management of Clouston syndrome involves treatment of palmar hyperkeratosis with emollients, keratolytics (e.g. 6% salicylic acid in 70% propylene glycol), topical retinoids, topical vitamin D ointment (calcipotriol) and systemic retinoids. Nonhealing or treatment‐resistant skin lesions should be biopsied to rule out squamous cell carcinoma.

 

References:

1. Clouston HR. A Hereditary Ectodermal Dystrophy. Can Med Assoc J. 1929;21(1):18-31.

2. Hassed SJ, Kincannon JM, Arnold GL. Clouston syndrome: an ectodermal dysplasia without significant dental findings. Am J Med Genet. 1996;61(3):274-276.

3. Escobar V, Goldblatt LI, Bixler D, Weaver D. Clouston syndrome: an ultrastructural study. Clin Genet. 1983;24(2):140-146.

4. Williams M, Fraser FC. Hydrotic ectodermal dysplasia--Clouston's family revisited. Can Med Assoc J. 1967;96(1):36-38.

5. Lamartine J, Munhoz Essenfelder G, Kibar Z, Lanneluc I, Callouet E, Laoudj D, et al. Mutations in GJB6 cause hidrotic ectodermal dysplasia. Nat Genet. 2000;26(2):142-144.