Refining the Phenotypic and Genotypic Spectrum of WDR73-Related Galloway-Mowat Syndrome: A Case Series and Systematic...

The aim of this report was to describe the phenotypic and genotypic spectrum of WDR73-related Galloway-Mowat syndrome (GAMOS).

This study comprises a case series conducted from January 2016 to October 2024, along with a systematic review of WDR73-related GAMOS. Analysis was performed on demographic data, clinical features, neuroimaging findings, neurodevelopmental outcomes, and WDR73 gene variants of eligible individuals.

We studied 64 individuals, including 4 from this case series and 60 from previous literature. The median reported age at disease onset ranged from 2.5 to 6 months. The most prevalent neurologic feature was microcephaly (55/64; 85.9%), followed by cerebellar atrophy (29/34; 85.3%), ocular abnormalities (54/64; 84.4%), axial hypotonia (52/64; 81.3%), and movement disorders (40/64; 62.5%). Proteinuria (37/64; 57.8%) was the leading extraneurologic feature while hiatal hernia (2/64; 3.1%) was the least observed classic feature. All individuals exhibited psychomotor impairment. A total of 18 WDR73 variants were identified, including 4 novel variants from this case series: c.21G > A (p.Trp7Ter), c.76G > A (p.Ala26Thr), c.214A > G (p.Arg72Gly), and c.884-171_c.*591del. Homozygous WDR73 variants were predominant (61/64; 95.3%) while 3 individuals carried compound heterozygous WDR73 variants.

WDR73-related GAMOS is an autosomal recessive, infantile-onset neurodevelopmental disorder with multisystem involvement. Recognizing its clinical manifestations prior to genetic testing may help mitigate reproductive risks and facilitate comprehensive, individualized health care.