A de novo CTNNB1 nonsense mutation associated with syndromic atypical hyperekplexia, microcephaly and intellectual disability: a case report. Issue 1 (December 2016) - Winczewska-Wiktor, Anna
Abstract Background In addition to its role in cell adhesion and gene expression in the canonical Wingless/integrated Wnt signaling pathway, β-catenin also regulates genes that underlie the transmission of nerve impulses. Mutations ofCTNNB1 (β-catenin) have recently been described in patients with a wide range of neurodevelopmental disorders (intellectual disability, microcephaly and other syndromic features). We for the first time associateCTNNB1 mutation with hyperekplexia identifying it as an additional candidate for consideration in patients with startle syndrome. Case presentation We describe an 11 year old male Polish patient with ade novo nonsense mutation inCTNNB1 who in addition to the major features ofCTNNB1 -related syndrome including intellectual disability and microcephaly, exhibited hyperekplexia and apraxia of upward gaze. The patient became symptomatic at the age of 20 months exhibiting delayed speech and psychomotor development. Social and emotional development was normal but mild hyperactivity was noted. Episodic falls when startled by noise or touch were observed from the age of 8.5 years, progressively increasing but never with loss of consciousness. Targeted gene panel next generation sequencing (NGS) and patient-parents trio analysis revealed a heterozygousde novo nonsense mutation in exon 3 ofCTNNB1 identifying a novel association of β-catenin with hyperekplexia. Conclusion We report for the first time a clear association of mutation inCTNNB1 with an atypical syndromic heperekplexia expanding the phenotype ofCTNNB1 -related syndrome. ConsequentlyCTNNB1 should be added to the growing list of genes to be considered as a cause of startle disease or syndromic hyperekplexia.