Ichthyosis, leukocyte vacuoles, alopecia, and sclerosing cholangitis

Other Names: NISCH syndrome; Neonatal ichthyosis-sclerosing cholangitis syndrome; ILVASC; Ichthyosis-sclerosing cholangitis syndrome

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.

Cause

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

Inheritance

Autosomal recessive inheritance, a 25% chance

NISCH syndrome shows an autosomal recessive pattern of inheritance.

Signs and symptoms

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 .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.

For most diseases, symptoms will vary from person to person. People with the same disease may not have all the symptoms listed. 80%-99% of people have these symptoms

• Hepatomegaly(Enlarged liver)
• Ichthyosis
• Jaundice(Yellow skin)
• Scarring alopecia of scalp
• Sparse and thin eyebrow(Thin, sparse eyebrows)
• Sparse body hair
• Sparse eyelashes(Scant eyelashes)
• Sparse scalp hair(Reduced/lack of hair on scalp)
• Splenomegaly(Increased spleen size)

5%-29% of people have these symptoms

• Abnormality of dental enamel(Abnormal tooth enamel)
• Acanthosis nigricans(Darkened and thickened skin)
• Hypodontia(Failure of development of between one and six teeth)
• Oligodontia(Failure of development of more than six teeth)
• Portal hypertension

Diagnosis

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.

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.

NIH genetic and rare disease info

• NIH info on Ichthyosis, leukocyte vacuoles, alopecia, and sclerosing cholangitis

Ichthyosis, leukocyte vacuoles, alopecia, and sclerosing cholangitis is a rare disease.

Ichthyosis, leukocyte vacuoles, alopecia, and sclerosing cholangitis Resources
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