What Is It, Causes, Treatment, and More
Author: Ashley Mauldin, MSN, ARPN, FNP-BC, CNE
Editors: Alyssa Haag, Ian Mannarino, MD, MBA, Kelsey LaFayette, DNP
Illustrator: Jessica Reynolds, MS
Copyeditor: David G. Walker
What is Joubert syndrome?
Joubert syndrome is a rare genetic disorder where the brain develops abnormally, causing an absent or underdeveloped cerebellar vermis (i.e., part of the brain that controls balance and coordination) and brainstem. The condition is typically apparent in infancy and more common in those of Ashkenazi Jewish, French-Canadian, and Hutterite ethnicities.There are numerous types of Joubert syndrome depending on the specific characteristics that the affected child presents with, which can include Joubert syndrome with retinal disease, Joubert syndrome with renal disease, Joubert syndrome with oculorenal disease, Joubert syndrome with oral-facial-digital features, and Joubert syndrome with hepatic disease.
What causes Joubert syndrome?
Joubert syndrome is typically inherited but can be sporadic. When inherited, there is a wide variety of genes implicated, including CPLANE1, TMEM67, AHI1, and CC2D2A. Joubert syndrome typically has an autosomal recessive inheritance pattern, meaning to have the condition, an individual must inherit two altered genes: one from each parent. There is a more rare form of Joubert syndrome that is inherited in an X-linked recessive pattern, which is when the altered gene is located on the X chromosome and mostly affects those assigned male at birth.The altered gene causes changes to the structure and function of primary cilia. Primary cilia are small projections that are located on the surface of cells, specifically cells in the brain, liver, and kidneys. They are responsible for the recognition of sensory input (e.g., sight, smell, hearing) and cell signaling during development. With this alteration to primary cilia, developmental and intellectual delays occur, though specific manifestations depend on the exact gene involved. For example, if the AHI1 gene is altered, then the individual will most likely have retinal dystrophy, which can cause impaired vision.
What are the signs and symptoms of Joubert syndrome?
The signs and symptoms of Joubert syndrome are often apparent during infancy and can vary widely but primarily include developmental or intellectual delays and low muscle tone (i.e., hypotonia). Other manifestations can include lack of muscle control (i.e., ataxia), abnormal breathing patterns (i.e., hyperpnea), sleep apnea, abnormal tongue and eye movement (i.e., nystagmus), and seizures. Other eye abnormalities can include widely spaced eyes, crossed eyes (i.e. strabismus), and visual impairment. Individuals may also present with anatomical abnormalities, such as tongue abnormalities, cleft lip or palate, and polydactyly (i.e., more than five fingers or toes on a single hand or foot).Additionally, other organ involvement can occur, resulting in liver and kidney disease.
How is Joubert syndrome diagnosed?
Joubert syndrome is diagnosed through a history and physical examination as well as with magnetic resonance imaging (MRI) of the brain. History and physical examination will reveal hypotonia and/or ataxia as well as developmental or intellectual delays. A brain MRI will show the molar tooth sign, which includes hypoplasia of the cerebellar vermis, a deep interpeduncular fossa, and thickened misoriented superior cerebellar peduncles—all of which resemble a molar tooth on MRI. In suspected cases with a genetic component, diagnosis can be confirmed with genetic testing.
How is Joubert syndrome treated?
Treatment for Joubert syndrome is usually supportive and aimed at addressing the affected child’s specific symptoms.
A child with intellectual or developmental delays may undergo physical therapy, speech therapy, and occupational therapy as well as educational support programs to provide help meeting their goals. If there are any respiratory or breathing issues, they may require supplemental oxygen, mechanical ventilation, or a tracheostomy. With eye abnormalities, surgery or corrective lenses may be required. And lastly, with any liver or kidney abnormalities, dialysis or kidney transplantation may be needed. While anatomical issues (e.g., polydactyly) can be treated surgically, symptoms (e.g., eizures) may be treated with medication.
Individuals with Joubert syndrome benefit from care through an interdisciplinary team, including neurologists, ophthalmologists, nephrologists, and geneticists as well as regular follow-up appointments to monitor the condition.
What are the most important facts to know about Joubert syndrome?
Joubert syndrome is a rare genetic disorder where the brain develops abnormally, thereby causing an absent or underdeveloped cerebellar vermis and brainstem. Joubert syndrome is most commonly an autosomal recessive disorder with the altered gene affecting the structure and function of primary cilia. Alterations in the primary cilia can cause issues with the developmental signaling pathways. The signs and symptoms of Joubert syndrome are often apparent during infancy and can vary widely but typically include hypotonia and intellectual and developmental delays. Joubert syndrome is diagnosed through a history; physical exam; brain MRI; and in genetic cases, can be confirmed with genetic testing. Treatment for Joubert syndrome is usually supportive and aimed at treating the affected child's specific symptoms.
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Resources for research and reference
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