Joubert/Meckel Gruber Syndrome Panel

Joubert syndrome and Meckel-Gruber syndrome are recessive neurodevelopmental conditions caused by pathogenic variants in proteins that are structural or functional components of the primary cilium. Primary cilia are essential for vertebrate development, and pathogenic variants affecting this organelle underlie a large group of human malformation syndromes, the ciliopathies. Both have variable phenotypes, extreme genetic heterogeneity, and display allelism both with each other and other ciliopathies.  Joubert syndrome is characterized by hypotonia, oculomotor apraxia, nystagmus, and intellectual disability. In these patients, brain MRI reveals the pathognomonic “molar tooth sign” with absent or hypoplastic cerebellar vermis, deepened interpenduncular fossa, and elongated superior cerebellar peduncles. The term Joubert syndrome and related disorders (JSRD) is used to describe individuals who, in addition to having the core neurological features, also have additional findings including retinal dystrophy, ocular colobomas, kidney disease, liver fibrosis, occipital encephalocele, oral hamartomas, endocrine abnormalities and polydactyly. Meckel Gruber syndrome is the most common syndromic form of neural tube defect and the classic triad of clinical features is characterized by occipital encephalocele, cystic kidneys and fibrotic changes to the liver. The clinical phenotype has since been broadened to include features such as postaxial polydactyly, skeletal dysplasia, microphthalmia, genital anomalies, cleft lip and palate, and heart defects. The panel includes sequence and deletion/duplication analysis of all the listed genes.