Ichthyosis, leukocyte vacuoles, alopecia, and sclerosing cholangitis

The following summary is from Orphanet, a European reference portal for information on rare diseases and orphan drugs.

Orpha Number: 59303

Definition

Neonatal ichthyosis-sclerosing cholangitis (NISCH syndrome) is a very rare complex ichthyosis syndrome characterized by scalp hypotrichosis, scarring alopecia, ichthyosis and sclerosing cholangitis.

Epidemiology

Less than ten patients (from unrelated consanguineous Moroccan families and from Sweden) have been reported so far.

Clinical description

The ichthyosis presents with diffuse white scales sparing the skin folds, and is accompanied by scalp hypotrichosis, cicatricial alopecia, and sparse eyelashes/eyebrows. Additional manifestations may include oligodontia, hypodontia and enamel dysplasia. All patients present with neonatal sclerosing cholangitis with jaundice and pruritus, hepatomegaly, and biochemical cholestasis. Overall, the clinical picture mimics biliary atresia (see this term). Portal hypertension, patent extrahepatic bile duct obstruction and splenomegaly may also be present. Histology shows extensive fibrosis and bile duct proliferation. Leukocyte vacuolization is a common finding. The hepatic disease may have variable expressivity, ranging from a progressive disease resulting in liver failure to regression of cholestasis.

Etiology

NISCH syndrome is caused by a mutation in the CLDN1 gene coding for the tight junction protein claudin-1.

Diagnostic methods

Diagnosis is based on clinical, biochemical and histological features.

Differential diagnosis

The differential diagnosis should include Dorfman-Chanarin syndrome and other syndromic forms of ichthyosis (see these terms).

Genetic counseling

NISCH syndrome shows an autosomal recessive pattern of inheritance.

Management and treatment

Treatments aim at improving symptoms and survival. Liver transplant remains the only effective treatment in case of liver failure. Ichthyosis is managed by hydration of the skin (topical application of creams and emollient oils), retinoids and sunlight exposure.

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