Walker Warburg syndrome (WWS) lies at the severe end of the spectrum of the congenital muscular dystrophies. WWS is a congenital disorder of the O-glycosylation that disrupts in the post-translation modification of dystroglycan proteins. WWS is characterized by the involvement of the central nervous system and rarely by multisystem involvement. Next-generation sequencing discovered that multiple genes are associated with this disorder. FKTN is the rarest cause of WWS. We describe a clinical-autopsy report of a molecularly- confirmed WWS case presenting with ventriculomegaly, agenesis of the corpus callosum with a novel phenotype of Dandy-Walker malformation and unilateral multi-cystic kidney. The whole-exome sequencing confirmed a homozygous variant (c.411C>A) in the FKTN gene with a premature termination codon. This case emphasizes the importance of detailed postnatal phenotyping through an autopsy in any pregnancy with antenatally identified malformations. Obstetricians, pediatricians as well as fetal medicine experts need to counsel the parents and focus on preserving the appropriate sample for genetic testing. WWS, though rare deserves testing especially in the presence of positive family history. Dandy-Walker malformation is a novel feature and expands the phenotypic spectrum.
Keywords
Congenital Disorder of Glycosylation, Walker-Warburg Syndrome, Hydrocephalus
References
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CotareloRP, ValeroMC, PradosB, et al. Two new patients bearing mutations in the fukutingene confirm the relevance of this gene in Walker-Warburg syndrome.
NabhanMM, ElKhateebN, BraunDA, et al. Cystic kidneys in fetal Walker-Warburg syndrome with POMT2 mutation: intrafamilial phenotypic variability in four siblings and review of literature.
AroraV, PuriRD, BhaiP, et al. The first case of antenatal presentation in COG8-congenitaldisorder of glycosylation with a novel splice site mutation and an extendedphenotype.
SframeliM, SarkozyA, BertoliM, et al. Congenital muscular dystrophies in the UK population: clinical and molecular spectrum of a large cohort diagnosed over a 12-year period.
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