Anxiety disorder is a common psychopathological comorbidity in patients with SHANK pathogenic variants: description of five new cases.

Researchers studied five children and teens with changes in SHANK genes (which are linked to autism). All five had autism, language delays, and motor skill delays. Most importantly, four out of five had anxiety disorders. This suggests that anxiety might be very common in people with SHANK gene changes, which could help doctors better understand and treat these children.

This study identified five patients (aged 6-18 years) with pathogenic variants in SHANK1, SHANK2, and SHANK3 genes through whole exome sequencing of 115 patients with mild intellectual disability and psychiatric comorbidities. All five patients presented with autism spectrum disorder, significant language and motor delays, and notably, four had generalised anxiety disorder while one had non-specific anxiety disorder. The research highlights anxiety disorders as a common psychopathological feature across SHANK gene variants, suggesting this may be an underrecognized but prevalent comorbidity in this genetic subgroup. The authors emphasize that genetic identification can improve clinical management through personalized approaches and enable precise genetic counselling for families.

Clinicians should screen for anxiety disorders in autism patients with SHANK gene variants. Genetic testing may inform personalized treatment approaches. Early identification could enable targeted interventions for both autism and anxiety symptoms, potentially improving outcomes through tailored therapeutic strategies.

Very small sample size (n=5) limits generalizability. Case series design without control group. Limited details on assessment methods or severity measures. No long-term follow-up data provided.

Pathogenic variants in the SHANK family genes have been linked to autism spectrum disorder, as well as to other neuropsychiatric and neurodevelopmental disorders. We aim to characterise the neurodevelopmental, neuropsychiatric and dysmorphic features of five additional patients with SHANK1 and SHANK2 and SHANK3 pathogenic variants to highlight a prevalent neuropsychiatric phenotype common to SHANK family members. Whole exome sequencing was performed in 115 patients (aged 6-18 years) with mild intellectual disability/borderline intellectual functioning and a psychiatric comorbidity. Neurodevelopmental, clinical, psychopathological and dysmorphological features of patients with pathogenic variants in SHANK genes were collected.

Intragenic pathogenic variants in SHANK1, SHANK2, and SHANK3 were identified in five patients. All patients presented significant language and motor delay and autism spectrum disorder as the most prevalent psychiatric comorbidity. Generalised anxiety disorder was present in four out of five patients, while one patient presented a non-specific anxiety disorder. This study identifies five new patients with pathogenic variants in the SHANK genes that present generalised anxiety disorder as a common psychopathological comorbidity.

Identification of the underlying genetic cause in children and adolescents with mild or borderline intellectual disability may improve their clinical management, allowing a personalized approach, and providing precise genetic counselling to the family.