Clinical Guidance
CTNNB1 neurodevelopmental disorder (CTNNB1-NDD) is characterized in all individuals by mild-to-profound cognitive impairment and in some individuals by exudative vitreoretinopathy. Exudative vitreoretinopathy, observed in up to 39% of reported individuals, is often diagnosed in early childhood and may present in infancy in those with significantly compromised vision . Other common findings include truncal hypotonia, peripheral spasticity, dystonia, behavior problems, microcephaly, and refractive errors and/or strabismus. Less common features include intrauterine growth restriction, feeding difficulties, and scoliosis. To date, at least 57 individuals have been identified with a pathogenic variant in CTNNB1 [, , , , , , , , , , , , , , , ]. The following description of the phenotypic features associated with CTNNB1-NDD is based on reports that included sufficient phenotypic information. (Note: Information on three individuals heterozygous for a pathogenic variant in a gene in addition to CTNNB1 are not included in or in the following discussion.) Table 2. Select Features of CTNNB1 Neurodevelopmental Disorder
Feature | # of Persons w/Feature / # Assessed | Comment |
|---|
Neurodevelopmental DD/ID | 57/57 (100%) | — |
Speech delay | 38/39 (97.4%) | — |
Motor delay | 36/36 (100%) | — |
Behaviorproblems | Autistic features | 19/41 (46.3%) |
ADHD | 7/41 (17.1%) | — |
Aggression/ self-mutilation | 18/37 (48.6%) | — |
Sleep disturbances | 9/26 (34.6%) | — |
Truncal hypotonia | 39/47 (83%) | — |
Peripheral spasticity | 43/48 (89.6%) | — |
Dystonia | 8/37 (21.6%) | — |
Ataxia | 10/28 (35.7%) | — |
Microcephaly | 42/52 (80.8%) | — |
Ophthalmologic1 Exudative vitreoretinopathy | 9/23 (39.1%) | Characterized by peripheral retinal avascularity, neovascularization w/secondary fibrosis, vessel pruning, retinal folds assoc w/exudates traction complicated by temporal dragging of macula vessels, retinal holes, retinal detachment |
Strabismus | 31/56 (55.4%) | — |
Refractive errors2 | 15/56 (26.8%) | Incl myopia, hypermetropia, astigmatism |
Other IUGR | 10/44 (22.7%) | — |
Short stature | 8/39 (20.5%) | — |
Feeding difficulties | 14/35 (40%) | — |
Scoliosis | 6/30 (20%) | ADHD = attention-deficit/hyperactivity disorder; DD = developmental delay; ID = intellectual disability; IUGR = intrauterine growth restriction Based on , , , , , , , , , , , , , , , 1. , , , , Myopia was detected in three of 56 reported individuals (5. |
Source: GeneReviews — "CTNNB1 Neurodevelopmental Disorder"
