Child Neurology: TRAPPC4-Related Neurodevelopmental Disorder

Area of Science:

• Genetics
• Neurology
• Rare Diseases

Background:

• A neurodevelopmental disorder associated with the TRAPPC4 gene was identified in 2020.
• This condition presents with epilepsy, spasticity, and brain atrophy, inherited in an autosomal recessive pattern.
• A high carrier frequency for TRAPPC4 variants necessitates increased diagnostic awareness.

Purpose of the Study:

• To report two sisters with homozygous pathogenic variants in the TRAPPC4 gene.
• To review the phenotypic spectrum of TRAPPC4-related neurodevelopmental disorder.
• To enhance recognition and consideration of this diagnosis in clinical practice.

Main Methods:

• Clinical investigation of two affected sisters.
• Genetic analysis to identify pathogenic variants in the TRAPPC4 gene.
• Literature review of the TRAPPC4-related neurodevelopmental disorder.

Main Results:

• Both sisters were found to have pathogenic homozygous variants (c.454+3A>G) in the TRAPPC4 gene.
• The diagnosis required extensive and time-consuming clinical evaluation.
• The study highlights the specific c.454+3A>G variant within the TRAPPC4 gene.

Conclusions:

• TRAPPC4-related neurodevelopmental disorder is a significant genetic condition requiring clinical vigilance.
• The homozygous pathogenic variant c.454+3A>G in TRAPPC4 is a key genetic cause.
• Raising awareness of this disorder can lead to earlier and more accurate diagnoses.