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.