Cerebellofaciodental syndrome in an adult patient: Expanding the phenotypic and natural history characteristics

• Published in: American journal of medical genetics. Part A Vol. 185; no. 5; pp. 1561 - 1568
• Main Authors: Honjo, Rachel Sayuri, Castro, Matheus Augusto Araújo, Ferraciolli, Suely Fazio, Soares Junior, Luiz Alberto Valente, Pastorino, Antonio Carlos, Bertola, Débora Romeo, Miyake, Noriko, Matsumoto, Naomichi, Kim, Chong Ae
• Format: Journal Article
• Language: English
• Published: Hoboken, USA John Wiley & Sons, Inc 01-05-2021; Wiley Subscription Services, Inc
• Subjects: adult; Cerebellum; Compression; dental; Developing countries; genetic; Heterozygosity; Hypoplasia; Intellectual disabilities; LDCs; Medulla oblongata; Patients; Rare diseases; Spinal cord; WES; genetic; WES; adult; dental; cerebellum
• ISSN: 1552-4825; 1552-4833
• DOI: 10.1002/ajmg.a.62140

Cerebellofaciodental syndrome is characterized by facial dysmorphisms, intellectual disability, cerebellar hypoplasia, and dental anomalies. It is an autosomal‐recessive condition described in 2015 caused by pathogenic variants in BRF1. Here, we report a Brazilian patient who faced a diagnostic challenge beginning at 11 months of age. Fortunately, whole‐exome sequencing (WES) was performed, detecting the BRF1 variants NM_001519.3:c.1649delG:p.(Gly550Alafs*36) and c.421C>T:p.(Arg141Cys) in compound heterozygosity, thus finally achieving a diagnosis of cerebellofaciodental syndrome. The patient is currently 25 years old and is the oldest patient yet reported. The clinical report and a review of published cases are presented. Atlanto‐occipital fusion, a reduced foramen magnum and basilar invagination leading to compression of the medulla‐spinal cord transition are skeletal findings not reported in previous cases. The description of syndromes with dental findings shows that such anomalies can be an important clue to relevant differential diagnoses. The cooperation of groups from different international centers made possible the resolution of this and other cases and is one of the strategies to bring medical advances to developing countries, where many patients with rare diseases are difficult to diagnose definitively.