FKTN Compound Heterozygosity Associated With Walker-Warburg Spectrum Features and Severe Cochlear Hypoplasia With...

Pathogenic fukutin (FKTN) variants cause different α-dystroglycanopathies, ranging from Fukuyama congenital muscular dystrophy to Walker-Warburg syndrome. We report a female neonate with compound heterozygous FKTN variants presenting with Walker-Warburg spectrum features and severe cochlear hypoplasia with preserved basal turn. The proband presented with marked hypotonia and early respiratory compromise at birth. Trio sequencing revealed compound heterozygous FKTN variants, including a common 3-kb founder insertion (NM_006731.2:c.4392_4393ins) and an early nonsense variant (NM_001079802.2:c.139C>T; p.Arg47Ter). Brain magnetic resonance imaging demonstrated extensive cobblestone lissencephaly and temporal bone imaging revealed bilateral severe cochlear hypoplasia with preserved basal turn and sensorineural hearing loss. Typical Walker-Warburg features such as hydrocephalus or a clear Z-shaped brainstem configuration were absent. This genotype, predicted to markedly reduce FKTN activity, likely caused severe α-dystroglycan dysfunction. The coexistence of cobblestone lissencephaly and cochlear hypoplasia suggests that profound α-dystroglycan impairment can affect both early organogenesis and later neuronal migration through altered extracellular matrix-dependent developmental signaling pathways. Overall, this case expands the phenotypic spectrum of FKTN-related dystroglycanopathy and highlights inner ear malformations as an under-recognized feature of severe FKTN deficiency.