Neonatal ichthyosis-sclerosing cholangitis syndrome

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ORPHA:59303OMIM:607626Q80.8
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Overview

Neonatal ichthyosis-sclerosing cholangitis syndrome, also known as NISCH syndrome, is a very rare inherited condition that affects the skin and the liver's bile ducts from birth. The name describes the two main features: 'ichthyosis' refers to dry, scaly skin, and 'sclerosing cholangitis' refers to scarring and narrowing of the tubes (bile ducts) that carry bile from the liver. NISCH syndrome is caused by changes in the CLDN1 gene, which provides instructions for making a protein called claudin-1. This protein helps hold cells tightly together in the skin and in the lining of bile ducts. Without it working properly, both the skin barrier and the bile duct structure break down. Babies with NISCH syndrome are often born with a tight, shiny skin covering called a collodion membrane, which peels away to reveal red, scaly skin underneath. Over time, the liver disease can become serious, leading to jaundice (yellowing of the skin and eyes), poor growth, and liver damage. The combination of skin and liver problems makes this condition challenging to manage. There is currently no cure for NISCH syndrome. Treatment focuses on managing symptoms — moisturizing the skin regularly, protecting it from infection, and monitoring and supporting liver function. In severe cases of liver disease, a liver transplant may be considered. Because this condition is so rare, care is best provided by a team of specialists working together.

Also known as:

Key symptoms:

Thick, scaly, dry skin present from birth (ichthyosis)Collodion membrane at birth — a tight, shiny skin layer that peels off in the first weeks of lifeRedness of the skin (erythroderma)Yellowing of the skin and eyes (jaundice) due to liver problemsItching caused by bile buildup in the bodyPoor weight gain and slow growthEnlarged liver or spleenScarring and narrowing of the bile ducts (sclerosing cholangitis)Elevated liver enzymes on blood testsAlopecia (hair loss or sparse hair)Leukonychia (white discoloration of the nails)

Clinical phenotype terms (15)— hover any for plain English
Scarring alopecia of scalpHP:0004552
Inheritance

Autosomal recessive

Passed on when both parents carry the same gene change; often skips generations

Age of Onset

Neonatal

Begins at or shortly after birth (first 4 weeks)

Orphanet ↗OMIM ↗NORD ↗

Treatments

No FDA-approved treatments are currently listed for Neonatal ichthyosis-sclerosing cholangitis syndrome.

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No actively recruiting trials found for Neonatal ichthyosis-sclerosing cholangitis syndrome at this time.

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Search ClinicalTrials.gov ↗Join the Neonatal ichthyosis-sclerosing cholangitis syndrome community →

No specialists are currently listed for Neonatal ichthyosis-sclerosing cholangitis syndrome.

View NORD Rare Disease Centers ↗Undiagnosed Disease Network ↗

Treatment Centers

8 centers
🏥 NORD

Baylor College of Medicine Rare Disease Center

Baylor College of Medicine

📍 Houston, TX

🏥 NORD

Stanford Medicine Rare Disease Center

Stanford Medicine

📍 Stanford, CA

🔬 UDN

NIH Clinical Center Undiagnosed Diseases Program

National Institutes of Health

📍 Bethesda, MD

🔬 UDN

UCLA UDN Clinical Site

UCLA Health

📍 Los Angeles, CA

🔬 UDN

Baylor College of Medicine UDN Clinical Site

Baylor College of Medicine

📍 Houston, TX

🔬 UDN

Harvard/MGH UDN Clinical Site

Massachusetts General Hospital

📍 Boston, MA

🏥 NORD

Mayo Clinic Center for Individualized Medicine

Mayo Clinic

📍 Rochester, MN

👤 Mayo Clinic Center for Individualized Medicine

🏥 NORD

UCLA Rare Disease Day Program

UCLA Health

📍 Los Angeles, CA

Travel Grants

No travel grants are currently matched to Neonatal ichthyosis-sclerosing cholangitis syndrome.

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Caregiver Resources

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Questions for your doctor

Bring these to your next appointment

  • Q1.What is the current state of my child's liver disease, and how will we monitor it over time?,What skin care routine and products do you recommend, and how often should we apply them?,Does my child need vitamin supplements, and which ones?,At what point would a liver transplant be considered, and what does that process involve?,Should other family members be tested as carriers of the CLDN1 gene change?,Are there any clinical trials or research studies we should know about?,What signs should prompt us to go to the emergency room?

Common questions about Neonatal ichthyosis-sclerosing cholangitis syndrome

What is Neonatal ichthyosis-sclerosing cholangitis syndrome?

Neonatal ichthyosis-sclerosing cholangitis syndrome, also known as NISCH syndrome, is a very rare inherited condition that affects the skin and the liver's bile ducts from birth. The name describes the two main features: 'ichthyosis' refers to dry, scaly skin, and 'sclerosing cholangitis' refers to scarring and narrowing of the tubes (bile ducts) that carry bile from the liver. NISCH syndrome is caused by changes in the CLDN1 gene, which provides instructions for making a protein called claudin-1. This protein helps hold cells tightly together in the skin and in the lining of bile ducts. Witho

How is Neonatal ichthyosis-sclerosing cholangitis syndrome inherited?

Neonatal ichthyosis-sclerosing cholangitis syndrome follows a autosomal recessive inheritance pattern. Genetic counseling can help families understand recurrence risk and testing options.

At what age does Neonatal ichthyosis-sclerosing cholangitis syndrome typically begin?

Typical onset of Neonatal ichthyosis-sclerosing cholangitis syndrome is neonatal. Age of onset can vary across affected individuals.