Joubert Syndrome (JS) is a rare genetic disorder characterized by cerebellar and brain stem malformation resulting in a “molar tooth” sign seen on brain imaging studies such as magnetic resonance imaging (MRI), increased rigidity and spasticity of muscles (hypertonia), and developmental delay. Brain stem malformation may lead to abnormal eye and tongue movements in addition to respiratory problems. JS may be seen in isolation or may be related to several other disorders including retinal dystrophy, renal disease, ocular colobomas (missing pieces of tissues in or around the eye), occipital encephalocele, hepatic fibrosis, polydactyl (extra fingers and toes), oral hamartomas (nodules of mature cells and tissues), seizures, and other abnormalities. Infants with JS may have abnormally rapid breathing (hyperpnea), decreased muscle tone (hypotonia), jerky eye movements (oculomotor apraxia), intellectual impairment, and the inability to coordinate voluntary muscle movements (ataxia). JS appears to be inherited in an autosomal recessive manner (meaning both parents must have a copy of the mutation) via mutation in a number of genes, including NPHP1, AHI1, and CEP290. JS typically has an autosomal X-linked recessive pattern of inheritance.
DIAGNOSTIC TESTING, PHYSICAL FINDINGS, AND ICD-9-CM CODING
Diagnostic testing: The diagnosis for JS is established by a combination of clinical examination and imaging studies of the midbrain and pons that resemble the characteristic molar tooth sign. Genetic testing for mutations are identified in about 50% of the people with JS, including the NPHP1, CEP290, AHI1, TMEM67 (MKS3), RPGRIP1L, CC2D2A, ARL13B, INPP5E, OFD1, TMEM216, KIF7, TCTN1, TCTN2, TMEM237, CEP41, TMEM138, C5orf42, TMEM231, and TCTN3 genes.
Physical findings: Hypotonia in infancy with later development of ataxia and developmental delays. Additional features in children with JS may include a large head, prominent forehead, high rounded eyebrows, epicanthal folds, ptosis, upturned nose with prominent nostrils, open mouth, tongue protrusion, rhythmic tongue motions, low-set and tilted ears.
ONSET AND PROGRESSION
Prognosis for children with Joubert Syndrome depends on the severity of the condition. The prognosis for infants with JS depends on whether or not the cerebellar vermis is partially developed or entirely absent. In some cases, the cerebellar vermis is almost fully developed, resulting in mild symptoms. The mildest form of the disease often results in mild lapses in motor control and mild intellectual disability. These individuals can live full, productive lives with medical and familial support.
There is no definitive treatment available for JS. Treatment is supportive and symptom specific. Infants and children with abnormal breathing may require stimulatory medications; supplemental oxygen; mechanical support; or tracheostomy in rare cases. Other interventions may include speech therapy; occupational and physical therapy; educational support including special programs for the visually impaired; and feedings by gastrostomy tube. Surgery may be required for polydactyl and symptomatic ptosis or strabismus. End-stage renal disease, liver failure or fibrosis is treated with standard medical approaches. Children may require annual evaluations of growth, vision, and liver and kidney function and, periodic neuropsychological and developmental testing.