Professionals

Overview:
Pathogenic variants in WDR4impair the METTL1–WDR4 tRNA methyltransferase complex responsible for installing the conserved m⁷G46 tRNA modification. Loss of this modification disrupts tRNA stability and global protein translation, particularly affecting organs with high developmental demands such as the brain and kidneys. As a result, WDR4–related disorders presents primarily with neurological, growth, and, in GAMOS6, renal manifestations.

Prevalence:
WDR4-related disorders are very rare. Reported cases include consanguineous families from Egypt, India, China, and Europe.

Clinical Spectrum:
•    GAMOS6 typically involves microcephaly, developmental delay, seizures, cerebellar or gyral abnormalities, and variable renal disease ranging from proteinuria to early-onset nephrotic syndrome.

•    MIGSB presents with severe congenital microcephaly, profound developmental disability, seizures, structural brain malformations, growth deficiency, skeletal findings, and facial dysmorphism.