BACKGROUND

Zaki syndrome is an autosomal recessive disorder caused by pathogenic variants in the WLS gene, which is essential for Wnt signaling. Altered Wnt signaling disrupts fetal development, organ formation, and tissue regeneration, leading to bone abnormalities and distinctive facial features. Key clinical characteristics of Zaki syndrome include specific facial features, microcephaly, skeletal anomalies, and eye malformations. However, the identification and diagnosis of Zaki syndrome remain challenging.

METHODS

The prenatal data and clinical information of a patient suspected of Zaki syndrome were retrospectively collected. Genetic testing and functional analysis were conducted to confirm the diagnosis of Zaki syndrome. Additionally, we conducted a literature search and review on Zaki syndrome.

RESULTS

A missense variant c.271G > A (p.Val91Met) and a splice site variant c.1279-1G > C in the WLS gene were identified. The diagnosis of Zaki syndrome was confirmed through genetic analysis and functional studies. Through the literature review, the clinical features of Zaki syndrome were refined. Further genotype-phenotype analysis suggested possible links between variant location and clinical features. Missense variants in the transmembrane region were associated with more cases of wide mouth and fewer cases of long fingers or toes. Variants near the ER signaling motif appeared more often with broad distal phalanges of the fingers.

CONCLUSION

Our study expanded the genetic and phenotypic spectrum of Zaki syndrome. It provided new insights into the prenatal and postnatal impact of WLS mutations and highlighted the early identification and intervention for Zaki syndrome.