Novel CTNNB1 Gene Variants in Spanish CTNNB1 Syndrome Patients: Clinical and Psychological Manifestations

CTNNB1 Syndrome is a neurodevelopmental disorder caused by de novo pathogenic variants characterized by global cognitive impairment, microcephaly, speech and motor delay, abnormal muscle tone, ophthalmologic impairments, behaviour problems and autistic spectrum disorder (ASD) symptoms. The aim of this study is to carry out a thorough clinical and psychological characterization of Spanish CTNNB1 syndrome patients. We used standard clinical assessment instruments and an ad hoc questionnaire to measure motor functioning, neurodevelopmental milestones, sleep problems, daily life activities, behavioural problems, communication and speech impairments, eating disorders and autistic features in 25 participants with CTNNB1 syndrome (15 females, 10 males; mean age 7.1 ± 4.1). Main clinical manifestations reported were microcephaly, motor impairment, sight problems, sleep disturbances and sensorial problems. Attainment of developmental milestones indicated motoric, language and daily living skills to be generally delayed. All participants had adaptative skills below their chronological age, even though verbal individuals had better functioning compared to nonverbal. Regarding behaviour impairments, CTNNB1 syndrome patients scored significantly high at internalizing and externalizing behavioural problems. Additionally, about 60% presented symptoms of ASD. Our findings have important implications for the psychotherapeutic and clinical approaches of CTNNB1 syndrome patients. We show the importance of early stimulation, given that an early attainment of developmental milestones is related to a current better function of many clinical variables. Moreover, previous underrated symptoms such as sleep problems, impaired adaptative skills and high rates of behavioural symptoms should be taken into consideration due to the harmful impact that have on every day life.