Joubert syndrome 2

Joubert Syndrome 2: A Rare Genetic Disorder

Joubert Syndrome 2 (JBTS2) is a rare genetic disorder that affects multiple parts of the body [2]. It is characterized by a specific hindbrain malformation, known as the "molar tooth sign" on brain MRI [9].

Key Features:

• Hindbrain Malformation: The most distinctive feature of JBTS2 is the presence of a molar tooth sign in the hindbrain, which is a characteristic cerebellar and brain stem malformation [5].
• Developmental Delays: Individuals with JBTS2 often experience developmental delays, including delayed speech and motor skills [4].
• Muscle Coordination Issues: People with JBTS2 may have difficulty coordinating muscle movements, leading to problems with balance and coordination [4].
• Eye Movement Abnormalities: Atypical eye movements are a common feature of JBTS2, which can include nystagmus (involuntary eye movements) [8].

Inheritance Pattern:

JBTS2 is inherited in an autosomal recessive pattern, meaning that both parents must have one copy of the mutated gene for their child to inherit the condition [5]. This means that each parent has a 50% chance of passing on the mutated gene to their offspring.

Other Symptoms:

• Hypotonia: Individuals with JBTS2 may experience hypotonia, which is a decrease in muscle tone.
• Sleep Apnea: Some people with JBTS2 may experience sleep apnea or other breathing abnormalities [7].
• Kidney Failure: In severe cases, individuals with JBTS2 may experience kidney failure, which can be life-threatening [11].

References:

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Common Features of Joubert Syndrome 2

Joubert syndrome 2 (JBTS2) is a rare genetic disorder that affects the brain and other vital structures. The signs and symptoms of this condition can vary widely among affected individuals, even within the same family.

• Infancy Symptoms: Many of the clinical symptoms of JBTS2 are apparent in infancy, including:
  • Lack of muscle control (ataxia)
  • Abnormal breathing patterns (hyperpnea)
  • Sleep apnea
  • Abnormal eye and tongue movements
  • Low muscle tone (hypotonia) [1]
• Developmental Delays: Children with JBTS2 often experience delayed acquisition of motor milestones, such as walking and balance. Cerebellar ataxia (staggering gait and imbalance) may develop later in life [9].
• Physical Differences: Individuals with JBTS2 may have distinctive facial features, including a prominent nose and thick eyebrows. They may also experience short stature and vision problems, such as myopia and strabismus [8][10].

Other Key Features

Some other key features of JBTS2 include:

• Abnormality of head or neck
• Depressed nasal bridge
• Abnormal foot morphology
• Abnormality of the eye
• Abnormality of limbs

It's essential to note that the signs and symptoms of JBTS2 can vary widely among affected individuals, even within the same family. A diagnosis is typically made through a combination of medical history, physical examination, brain MRI, and genetic testing.

References

[1] Signs & Symptoms. Many of the clinical symptoms of Joubert syndrome are apparent in infancy and most affected children have delays in gross motor milestones. [8] Some other key features are short stature, vision problems (e.g, myopia, strabismus), distinctive facial features (e.g, prominent nose, thick eyebrows, long ... [9] During infancy, hypotonia may appear. Cerebellar ataxia (staggering gait and imbalance) may develop later. Delayed acquisition of motor milestones is common. [10] What are the symptoms of Joubert syndrome? Joubert syndrome causes different conditions and may change as children grow up. Symptoms may include physical differences, including facial differences, symptoms of certain eye conditions, and liver and kidney disease. Your child may have the following neurological issues or conditions:

Diagnostic Tests for Joubert Syndrome 2

Joubert syndrome 2 (JBTS2) is a rare genetic disorder that can be diagnosed through various tests. The diagnostic process typically involves a combination of clinical evaluation, imaging studies, and molecular genetic testing.

• Molecular Genetic Testing: This is the most definitive test for JBTS2, which can confirm the presence of a pathogenic variant in the TMEM216 gene. Molecular genetic testing can be performed on blood or tissue samples.
  • According to search result [8], the Joubert syndrome 2 test offers molecular detection of one pathogenic variant in the TMEM216 gene, R73L (c.218G>T), which accounts for a significant proportion of cases.
• Imaging Studies: Imaging studies such as MRI and CT scans can help identify characteristic features of JBTS2, including the molar tooth sign.
  • Search result [3] mentions that the molar tooth sign got its name because the characteristic brain abnormalities resemble the cross-section of a molar tooth when seen on an MRI.
• Clinical Evaluation: A thorough clinical evaluation by a healthcare professional is essential to diagnose JBTS2. This includes assessing symptoms, medical history, and physical examination.
  • Search result [10] suggests that a primary care physician (PCP) can help with specialist referrals, ordering diagnostic tests, and coordinating providers as part of the diagnostic process.

Additional Tests

Other tests may be performed to rule out other conditions or to assess the severity of JBTS2. These include:

• Carrier Screening: Carrier screening for JBTS2 is available for individuals of Ashkenazi Jewish descent.
  • Search result [4] mentions that carrier screening or diagnostic testing for Joubert syndrome type 2 for individuals of Ashkenazi Jewish descent can be performed on a 3 mL whole blood sample.
• Prenatal Testing: Prenatal testing is feasible through genetic testing where both disease-causing mutations have been previously identified in an affected family member.
  • Search result [5] suggests that antenatal diagnosis is possible through genetic testing.

Genetic Panel

A 36 gene panel that includes assessment of non-coding variants may be ideal for patients with a clinical suspicion of JBTS2. Search result [7] mentions that this panel can help identify the underlying cause of JBTS2 in individuals with a clinical suspicion of the disorder.

Treatment Overview

Joubert syndrome 2 (JBTS2) is a rare genetic disorder that affects various parts of the body, including the brain, kidneys, and liver. While there is no cure for JBTS2, treatment focuses on managing symptoms and supporting affected individuals.

Medications for Supportive Care

According to search results [1], medications are used to support decreasing kidney function in individuals with JBTS2. This may include:

• Medications for hypertension (high blood pressure)
• Fluid management to prevent dehydration in early disease and fluid overload in late disease
• Dialysis or kidney transplantation in cases of end-stage kidney disease (ESKD)

Other Treatment Options

In addition to medications, supportive care is essential for individuals with JBTS2. This may include:

• Infant stimulation and physical therapy to support motor development [12]
• Ophthalmologic treatment for eye-related symptoms [15]
• Seizure management through appropriate medication based on the type of seizure [14]

Current Research

Research studies have explored various treatment options, including CDK inhibitors, SHH agonists, and mTOR pathway inhibitors such as rapamycin [6]. However, these treatments are still in the experimental stage.

Symptomatic Treatment

As JBTS2 is a complex disorder with varying symptoms, treatment plans are tailored to address specific needs. A medical team can provide regular examinations and support to manage symptoms as they arise [7].

References:

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The differential diagnosis for Joubert syndrome 2 (JS2) includes several conditions that can present with similar clinical features, such as mid-hindbrain malformation, developmental delay, hypotonia, oculomotor apraxia, and breathing abnormalities.

Some of the conditions that need to be considered in the differential diagnosis of JS2 are:

• Meckel syndrome (MIM PS249000): This is a genetically and phenotypically overlapping ciliopathy with JS2. It likely represents the severe end of a Joubert-Meckel spectrum.
• Oral-facial-digital syndrome (MIM PS311200)
• Acrocallosal syndrome (MIM 200990)
• Mainzer-Saldino syndrome (MIM 266920)
• COACH syndrome (MIM 216360, Cerebellar vermis hypo/aplasia)

These conditions can present with similar clinical features to JS2 and may require further evaluation to rule out or confirm the diagnosis.

According to [12], the differential diagnosis for Joubert syndrome 2 also includes other ciliopathies such as Meckel syndrome, which likely represents the severe end of a Joubert-Meckel spectrum. Additionally, [11] mentions that the differential diagnosis should consider genetically and phenotypically overlapping ciliopathies.

It's worth noting that for the majority of JS patients, the diagnosis is not problematic if neuroimaging shows the molar tooth sign, which is the hallmark feature of Joubert syndrome [14].