CTNNB1‐related neurodevelopmental disorder in a Chinese population: A case series

Abstract

CTNNB1‐related disorder is an autosomal dominant neurodevelopmental disorder characterized by a variable degree of cognitive impairment, microcephaly, truncal hypotonia, peripheral spasticity, visual defects, and dysmorphic features. In this case series, we report the clinical and molecular findings of nine Chinese patients affected by CTNNB1‐related disorders. The facial features of these affected individuals appear to resemble what had been previously described, with thin upper lip (77.8%) and hypoplastic alae nasi (77.8%) being the most common. Frequently reported clinical characteristics in our cohort include developmental delay (100%), peripheral spasticity (88.9%), truncal hypotonia (66.7%), microcephaly (66.7%), and dystonia (44.4%). While various eye manifestations were reported, two affected individuals (22.2%) in our cohort had familial exudative vitreoretinopathy. One of the affected individuals had craniosynostosis, a feature not reported in the literature before. To our knowledge, this is the first reported Chinese case series of CTNNB1‐related neurodevelopmental disorders. Further studies are required to look into whether ethnic differences play a role in phenotypic variations.

The extended clinical and genetic spectrum of CTNNB1-related neurodevelopmental disorder

“…As already linked with NEDSDV (MIM# 615075) and exudative vitreoretinopathy 7 (MIM# 617572), clinical features such as developmental delay, intellectual disability, spastic diplegia, and ocular problems have been well established in CTNNB1-related neurodevelopmental disorder (1,(3)(4)(5)(6)(7)(8). Although most of our patients shared such key phenotypes, the severity of each symptom was different patient by patient.…”

“…Although we searched for associations between mutation type or location and disease phenotype, we could not find any significant genotype-phenotype correlations in our cohort. A recent study also reported that no genotypephenotype correlations have been identified in CTNNB1-related neurodevelopmental disorder to date (15,29).…”

“…In addition, none of our patients had any seizure history during follow-up. As shown in Figure 2A, we reviewed a total of 69 patients with CTNNB1-related neurodevelopmental disorder reported in the literature, including our patients, and found that only one (1.4%) and three (5.4%) patients had seizure history and brain abnormalities, respectively (1,(3)(4)(5)(6)(7)(8)(9)(10)(11)(13)(14)(15). The patient with seizure history was suspected as having absence seizure in early childhood.…”

“…Interestingly, all three patients with autistic features were female in this study. Autistic features have been reported frequently (1,(3)(4)(5)(6)(7)(8)(9)(10)(11)(13)(14)(15), shown in around 30% of patients with CTNNB1-related neurodevelopmental disorder (Figure 2A). Consistent with our study, autistic features were significantly more frequent in female patients (54.3%, 19 out of 35) than in male patients (5.9%, 2 out of 34) with a P-value = 1.3 × 10 −5 by Fisher's exact test (Figure 2B).…”

“…This is an autosomal dominant disorder, mostly caused by loss-offunction mutations resulting in disruption of normal molecular function. Although several studies had reported additional cases of NEDSDV, their clinical presentations are different from each other (1,(3)(4)(5)(6)(7)(8)(9)(10)(11).…”