Joubert syndrome with hepatic defect

Joubert syndrome with hepatic defect, also known as Joubert syndrome type 2 or COACH syndrome (Cerebellar vermis hypoplasia, Oligophrenia, Ataxia, Coloboma, and Hepatic fibrosis), is a rare genetic disorder belonging to the group of Joubert syndrome and related disorders (JSRD). It is characterized by the hallmark 'molar tooth sign' on brain MRI, which reflects hypoplasia or aplasia of the cerebellar vermis and abnormalities of the brainstem. In addition to the central nervous system involvement, this subtype is distinguished by significant liver disease, most commonly congenital hepatic fibrosis, which can progress to portal hypertension and liver dysfunction over time. Affected individuals typically present in infancy or early childhood with hypotonia, developmental delay, intellectual disability of variable severity, abnormal eye movements (including oculomotor apraxia), and episodic abnormal breathing patterns such as alternating tachypnea and apnea in the neonatal period. Ocular colobomas and retinal dystrophy may also be present. The hepatic involvement can range from subclinical fibrosis detected on biopsy to clinically significant portal hypertension with hepatosplenomegaly. Some patients may also develop kidney abnormalities, including nephronophthisis, which can lead to progressive renal insufficiency. Joubert syndrome with hepatic defect is caused by mutations in several genes involved in the structure and function of primary cilia, including TMEM67 (also known as MKS3), CC2D2A, and RPGRIP1L, among others. These genes encode proteins essential for ciliary signaling, and their dysfunction underlies the multi-organ manifestations of the disease. There is currently no cure for this condition. Management is supportive and multidisciplinary, involving neurological rehabilitation, monitoring and treatment of liver and kidney complications, ophthalmologic care, and developmental therapies. Regular surveillance of hepatic and renal function is essential, and in severe cases, liver or kidney transplantation may be considered.

Data sourced from FDA regulatory filings and ClinicalTrials.gov. Updated periodically.

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