ESPE Abstracts

Cerebellar-facial-dental syndrome is a rare autosomal recessive disorder due to biallelic variants in the BRF1 gene. It is characterised by cerebellar hypoplasia, intellectual disability, dysmorphic facial features and short stature. There have been only 12 patients described in the literature to date. We report a case of a 9-year-old non-consanguineous Caucasian boy with cerebellar-facial-dental syndrome and multiple coexisting diagnoses, including Klinefelter syndrome (XXY karyotype), confirmed growth hormone deficiency, alpha-1-antitrypsin deficiency (SZ phenotype) and focal epilepsy. He is pre-pubertal, with otherwise stable pituitary function and normal pituitary on MRI. Both the patient and his brother have cerebellar-facial-dental syndrome with biallelic variants c.413T>C l.Leu138Pro (maternally inherited) and c.422G>A p.Arg141His (Paternally inherited) in the BRF1 gene. The patient’s brother shares several features of the syndrome, but does not have the coexisting diagnoses of Klinefelter syndrome, growth hormone deficiency and alpha-1-antitrypsin deficiency. We confirm features of cerebellar-facial-dental syndrome previously described in the literature, including cerebellar hypoplasia, microcephaly, short stature, scoliosis, dysmorphic facial features, learning difficulties and sensorineural hearing loss. This combination of diagnoses has not been described previously and illustrates the role of genetics, imaging and a multidisciplinary approach in diagnosing and managing children with complex clinical features.