Neonatal-ithyosis-sclerosing-cholangitis-syndrome Q80.8; K83.0

Gould 1845; Baala et al. 2002

The very rare autosomal recessive complex genodermatosis, which occurs already in the neonatal period, is clinically conspicuous by a pronounced icterus with hepatomegaly and pruritus (sclerosing cholangitis). The ichthyotic changes are trunk-accentuated, rather mild. More striking is the frontal hypotrichosis (scarring alopecia) of the scalp.

< 20 patients have been described so far as sporadic cases and in unrelated consanguine Moroccan families and in Sweden (Szepetowski S et al. (2017).

Detectable are (so far 3 different) mutations in the CLDN1 gene (3q28-q29), which codes for claudin-1, a protein of the "tight junctions" (Grosse B et al.2012 - see below cell contacts). In the"niche liver", claudin-1 is no longer expressed in hepatocytes or cholangiocytes.

All patients come with neonatal sclerosing cholangitis with icterus, pruritus, hepatomegaly. Inernistically, the syndrome mimics the clinical picture of biliary atresia. The severity of the liver disease can vary, from a progressive course with hepatic insufficiency up to a bland course with regression of cholestasis.

The symptoms of ichthyosis are truncated, diffuse white scaling; the joint bends are left out. Accompanying symptoms are flat scaling of the scalp, hypotrichosis, scarred alopecia and thinned eyebrows and eyelashes.

Other potential symptoms are:

• Teeth: Oligodontia, hypodontia and enamel hypoplasia.
• Gastroenterologically: portal hypertension, open extra-hepatic bile duct, splenomegaly.

Laboratory parameters of a cholestasis.

Dilated fibrosis and proliferation of the bile ducts. Vacuolated leukocytes are conspicuous.

Skin findings with ichthyosis and alopecia; icterus: clarification by cholangiography; sonography, liver biopsy

The treatment is symptomatic. In case of liver failure, liver transplantation is an absolute necessity.

Ichthyosis is treated by hydration of the skin (topical application of skin care creams and skin care oils); gfls.UV therapy.

Prognosis and course of the disease depend exclusively on the severity and course of the liver disease.

1. Grosse B et al(2012) Claudin-1 involved in neonatal ichthyosis sclerosing cholangitis syndrome regulates hepatic paracellular permeability. Hepatology 55:1249-1259.
2. Khalifa C et al (2018) Anesthetic Care of 2 Siblings With Neonatal Ichthyosis and Sclerosing Cholangitis Syndrome: Case Reports. A A Pract 11:216-218.
3. Kirchmeier P et al (2014) Novel mutation in the CLDN1 gene in a Turkish family with neonatal ichthyosis sclerosing cholangitis (NISCH) syndrome. Br J Dermatol 170:976-978.
4. Szepetowski S et al (2017) NISCH syndrome, a rare cause of neonatal cholestasis: A case report. Arch Pediatr 24:1228-1234.