| Neonatal ichthyosis-sclerosing cholangitis syndrome
caused by a novel CLDN1 mutation: a case report and
literature review |
Upasana Ghosh1 
, Ankit Agrawal1
, Varunvenkat M Srinivasan2
, Rani Manisha2
, Umesh Shukla1
, Vikas Jain1
, Mayank Nilay2
, Harish Kumar3 |
1Department of Pediatric Gastroenterology, Post Graduate Institute of Child Health, Noida, Uttar Pradesh, India
2Department of Medical Genetics, Post Graduate Institute of Child Health, Noida, Uttar Pradesh, India
3Bal Chikista Kendra, Mauzaffarnagar, Uttar Pradesh, India |
Correspondence:
Mayank Nilay, Email: mnilay21@gmail.com
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Received: 19 April 2025 • Revised: 8 July 2025 • Accepted: 9 July 2025 |
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| Abstract |
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Neonatal ichthyosis-sclerosing cholangitis syndrome
(NISCH) is an autosomal recessive disorder characterized
by cholestasis, generalized ichthyosis, alopecia, and
dental anomalies. As this is a rare syndrome, here we
present a case caused by a novel mutation followed by a
literature review of all published cases. This retrospective
review includes all original articles on the clinical profiles
of all 37 cases published through December 2024 using a
PubMed search. The patient was a 2-month-old boy who
presented with cholestasis, sparse hair, and generalized
ichthyosis. Whole-exome sequencing revealed a novel
pathogenic variation in exon 1 of the CLDN1 gene:
(NM_021101.5) c.36dupT (p.Leu13SerfsTer56). The patient
was symptomatically managed, and his condition improved.
Among the 37 reported cases, the median age at
diagnosis was 60 months (range, 1–636 months). Patients
of Moroccan ethnicity were most commonly affected,
and c.200_201delTT was the most common mutation.
Among the clinical features, ichthyosis was universal
(37 of 37 [100%]), followed by jaundice in 70.2% (26 of 37),
pruritus in 38.2% (13 of 34), hepatomegaly in 43.3% (13 of
30), and splenomegaly in 23.8% (5 of 21) of patients. Portal
hypertension (7 of 35 [20%]) and mental retardation (3 of
21 [14.2%]) were rare. The disease phenotype varied from
no liver involvement or transient neonatal cholestasis
to end-stage liver disease. Progressive liver disease was
reported in 8 patients, five of whom underwent liver
transplantation. NISCH is a rare syndrome with variable
phenotypes ranging from no liver involvement and
transient neonatal cholestasis to advanced liver disease
requiring liver transplantation. Therefore, a multidisciplinary
approach with close follow-up is required. |
| Key Words:
NISCH syndrome, Sclerosing cholangitis,
Claudin 1, Cholestasis, Ichthyosis |
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