Individuals with CIC haploinsufficiency syndrome present with a clinical spectrum of neurodevelopmental features. The most penetrant phenotype affecting >90% of patients is developmental delay/intellectual disability, however, the severity can vary from mild developmental delay to severe intellectual disability. Other neurodevelopmental features observed include autism spectrum disorder, epilepsy, and attention deficit hyperactivity disorder. Additionally, some individuals have presented with cardiovascular abnormalities including pulmonary stenosis and heart murmurs.
Somatic mutations in CIC have been observed in a number of cancers, including hematopoietic malignancies (t-cell lymphoblastic lymphoma) and oligodendroglioma and can occur independently of CIC haploinsufficiency syndrome. One patient with CIC haploinsufficiency developed acute lymphoblastic leukaemia (ALL). There is not sufficient evidence to determine if patients with CIC haploinsufficiency syndrome are at increased risk of cancer, however, we recommend routine cancer screening in all patients with CIC haploinsufficiency syndrome as a preventative measure.