Human CNTNAP1 Variants Associated With Severe Neurological Deficits: Additional Cases and Literature Review

Area of Science:

• Neuroscience
• Genetics
• Molecular Biology

Background:

• Contactin-Associated Protein 1 (CNTNAP1/Caspr1) is crucial for nervous system function, organizing myelinated axon domains.
• Proper CNTNAP1 function enables saltatory conduction, vital for rapid neuronal communication.

Purpose of the Study:

• To compile and analyze all reported cases of biallelic CNTNAP1 variants.
• To present seven new cases, expanding the total to 54 individuals.
• To elucidate the phenotypic spectrum and key clinical features associated with CNTNAP1 mutations.

Main Methods:

• Systematic review of published literature on CNTNAP1 variants.
• Inclusion of seven newly identified patient cases.
• Detailed analysis of genetic variants and associated clinical manifestations.

Main Results:

• A total of 54 individuals with biallelic CNTNAP1 variants were analyzed.
• Common clinical features include respiratory distress, generalized hypotonia, hypomyelination, intellectual disabilities, and reduced life expectancy.
• Phenotypic presentation shows significant diversity despite recurring key symptoms.

Conclusions:

• Biallelic CNTNAP1 variants result in a spectrum of neurological disorders, often severe.
• Understanding the genotype-phenotype correlation is crucial for diagnosis and management.
• Further research is needed to explore therapeutic strategies for CNTNAP1-related disorders.