Overview
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📜 Demographic Information:
- Incidence: Approximately 1 in 80,000 to 100,000 live births
- Prevalence: Rare, with several hundred cases reported worldwide
- Gender: Affects both males and females equally
- Onset Age: Symptoms typically present in infancy
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📜 Coding:
- ICD-11: LD26.8 - Other specified malformations of the cerebellum
- OMIM: 213300 - Joubert Syndrome
- UMLS: C0175713
- MeSH: C536620
- GARD: 6021
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Overview
Joubert Syndrome (JS) is a rare genetic disorder characterized by a malformation of the brainstem and cerebellar vermis, leading to symptoms such as hypotonia, ataxia, abnormal breathing patterns, and developmental delays. Diagnosis is based on MRI findings and genetic testing. Management involves medical interventions, assistive technologies, and therapeutic techniques aimed at maximizing developmental potential and supporting daily living.
Key Features
- Neurological: Hypotonia (decreased muscle tone), ataxia (lack of muscle control), developmental delays, and intellectual disabilities. Many patients also experience nystagmus (rapid, involuntary eye movements), strabismus (crossed eyes), and oculomotor apraxia (difficulty moving the eyes side to side).
- Respiratory: Abnormal breathing patterns such as episodic hyperpnea (abnormally rapid breathing) and apnea (pauses in breathing).
- Renal and Hepatic: Kidney and liver abnormalities including nephronophthisis (a type of kidney disease) and hepatic fibrosis.
- Skeletal: Polydactyly (extra fingers or toes), scoliosis (curvature of the spine), and facial dysmorphisms like a prominent nasal bridge.
- Other Systems: Cleft lip or palate, tongue abnormalities, and situs inversus totalis (organs on the opposite side of the body).
Medical Features and Pathophysiology
Pathophysiology
- Genetic Basis: JS is caused by mutations in one of at least 34 genes that are involved in the structure and function of primary cilia, which are small, hair-like structures on the surface of cells that play critical roles in cell signaling and function. The most commonly affected genes include AHI1, NPHP1, CEP290, and TMEM67. The inheritance pattern is usually autosomal recessive, meaning both parents must carry one copy of the mutated gene.
- Malformation: JS is characterized by a malformation of the brainstem and cerebellar vermis, which is responsible for balance and coordination. This malformation creates a distinctive "molar tooth sign" visible on brain MRIs. The syndrome affects multiple body systems and can lead to a range of symptoms including hypotonia, ataxia, abnormal breathing patterns, and developmental delays.
Symptoms
Neurological
- Hypotonia (decreased muscle tone)
- Ataxia (lack of muscle control)
- Developmental delays