X-linked Joubert syndrome: Neuroimaging and clinical features associated with a novel mutation in oral-facial-digital syndrome type 1

Abstract

Oral-facial-digital syndrome type 1 (OFD1; OMIM#311200) is a rare developmental disorder characterized by cra- niofacial, oral, skeletal abnormalities, cystic kidneys and neurological involvement including mental retardation. The syndrome is caused by mutations in the OFD1 gene and results in male lethality in the first or second trimester. The spectrum of phenotypes associated with mutations in OFD1 continues to expand, and genotype-phenotype correlations are beginning to be recognized. The spectrum includes Simpson-Golabi-Behmel syndrome type 2 (OMIM#300209) and X-linked Joubert syndrome (type 10) phenotype in addition to the classical OFD1 phenotype with early male lethality. We describe the neuroimaging and clinical findings in a 17-year-old male with a clinical diagnosis of Joubert syndrome associated with a novel mutation in the OFD1 gene (type 10). Our patient confirms the reported association of OFD1 mutation with X-linked recessive Joubert syndrome. This family is the fifth reported with X-linked Joubert syndrome, associated with a novel mutation in exon 17 of the OFD1 gene. We describe unique neuroimaging and clinical features associated with OFD1 mutations and highlight the utility of advanced neu- roimaging techniques in characterizing the phenotype.