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CNTNAP1-Related Congenital Hypomyelinating Neuropathy
Harry Lesmana1, Marissa Vawter Lee2, Seyed Ali Hosseini3
1Department of Hematology, St. Jude Children's Research Hospital, University of Tennessee Health Science Center, Memphis, Tennessee; Department of Oncology, St. Jude Children's Research Hospital, University of Tennessee Health Science Center, Memphis, Tennessee.
Congenital hypomyelinating neuropathy caused by contactin-associated protein 1 (CNTNAP1) mutations affects the central and peripheral nervous systems. This rare condition presents with severe hypotonia and can have variable outcomes, including survival beyond infancy.
Area of Science:
- Genetics and Neurology
- Rare Diseases
- Peripheral Neuropathy
Background:
- Congenital hypomyelinating neuropathy is a rare inherited peripheral neuropathy.
- Characterized by weakness, hypotonia, and reduced nerve conduction.
- Mutations in contactin-associated protein 1 (CNTNAP1) are a known cause.
Observation:
- Whole-exome sequencing identified a novel CNTNAP1 mutation in two siblings with congenital hypotonia.
- Phenotypic data were compared with 17 previously reported patients with CNTNAP1 mutations.
- All patients exhibited severe hypotonia, respiratory distress, and cranial nerve palsies at birth.
Findings:
- A novel, heterozygous compound mutation in CNTNAP1 was identified.
- Six of 19 patients survived infancy, requiring mechanical ventilation.
- Seizures were common in surviving patients, indicating potential central nervous system involvement.
Implications:
- CNTNAP1-related neuropathy is a distinct hereditary disorder affecting both central and peripheral nervous systems.
- No clear phenotype-genotype correlation was observed.
- Arthrogryposis multiplex congenita and early lethality are not universal outcomes.
