Joubert syndrome 28

Joubert Syndrome: A Rare Genetic Disorder

Joubert syndrome is a rare genetic disorder that affects brain development, causing muscle control, breathing, and eye movement issues [2]. The most common features of Joubert syndrome are lack of muscle control (ataxia), abnormal breathing patterns (hyperpnea), sleep apnea, abnormal eye movements, and developmental delays [3].

Key Characteristics:

• Brain Development Abnormalities: Joubert syndrome causes abnormalities in the cerebellum vermis and brainstem, resulting in the "molar tooth sign" on MRI [1].
• Muscle Control Issues: Lack of muscle control (ataxia) is a common feature of Joubert syndrome.
• Breathing Problems: Abnormal breathing patterns (hyperpnea), sleep apnea, and other respiratory issues are also associated with Joubert syndrome.
• Eye Movement Abnormalities: Abnormal eye movements are another characteristic of this rare disorder.

Other Features:

• Developmental Delays: Children with Joubert syndrome often experience developmental delays.
• Cognitive Impairment: Some individuals may experience cognitive impairment, affecting their mental and physical abilities.
• Visual Impairments: In some cases, Joubert's syndrome can cause varying degrees of visual impairments.

References:

[1] Jul 1, 2017 — Joubert syndrome causes abnormalities in the cerebellum vermis and brainstem, resulting in the "molar tooth sign" on MRI. [2] Joubert syndrome is a rare genetic disorder that affects brain development, causing muscle control, breathing, and eye movement issues. [3] Jun 14, 2021 — The most common features of Joubert syndrome are lack of muscle control (ataxia), abnormal breathing patterns (hyperpnea), sleep apnea, abnormal ... [4] by M Parisi · 2017 · Cited by 128 — Joubert syndrome (JS) has three primary findings: a cerebellar and brain stem malformation (MTS), hypotonia, and developmental delays. [5] A rare, autosomal recessive congenital cerebellar ataxia characterized by congenital malformation of the brainstem and agenesis or hypoplasia of the cerebellar ... [6] Joubert's syndrome is a rare disorder affecting the brain, causing varying degrees of physical, mental and sometimes visual impairments. [7] by F Brancati · 2010 · Cited by 556 — Joubert syndrome (JS) and related disorders (JSRD) are a group of developmental delay/multiple congenital anomalies syndromes in which the obligatory hallmark ... [8] Joubert Syndrome is a group of recessive disorders characterized by cerebellar hypoplasia, cognitive impairment, low muscle tone, and eye movement abnormalities. [9] Dec 20, 2023 — Joubert syndrome is a rare genetic condition that causes underdevelopment in a part of the brain and malformation of the brainstem.

Common Signs and Symptoms of Joubert Syndrome

Joubert syndrome is a rare genetic condition that affects the brain, causing various symptoms to appear in infancy and later in life. The signs and symptoms can vary among affected individuals, even within the same family.

• Neurological Issues: Affected children may experience lack of muscle control (ataxia), abnormal breathing patterns (hyperpnea), sleep apnea, abnormal eye and tongue movements, and low muscle tone.
• Physical Differences: Joubert syndrome can cause physical differences, including facial features that are distinct from others. Eye conditions and liver and kidney disease may also be present.
• Brain Abnormalities: The hallmark feature of Joubert syndrome is a combination of brain abnormalities known as the molar tooth sign, which can be seen on brain imaging studies such as MRI.

Common Features in Infancy

Many of the clinical symptoms of Joubert syndrome are apparent in infancy and most affected children have delays in gross motor milestones. The most common features include:

• Weak muscle tone (hypotonia)
• Abnormal breathing patterns
• Abnormal eye movements
• Ataxia
• Distinctive facial features
• Intellectual disability

Later Developmental Delays

Cerebellar ataxia (staggering gait and imbalance) may develop later in life. Delayed acquisition of motor milestones is common, and cognitive abilities are variable.

These symptoms can vary widely among affected individuals, making diagnosis challenging. However, a combination of history, physical exam, brain MRI, and genetic testing can confirm the presence of Joubert syndrome.

References

• [1] Symptoms may include physical differences, including facial differences, symptoms of certain eye conditions, and liver and kidney disease.
• [4] Many of the clinical symptoms of Joubert syndrome are apparent in infancy and most affected children have delays in gross motor milestones.
• [5] Signs and symptoms can vary but commonly include weak muscle tone (hypotonia); abnormal breathing patterns; abnormal eye movements; ataxia; distinctive facial features; and intellectual disability.
• [7] Most of the signs and symptoms of the Joubert syndrome appear very early in infancy with most children showing delays in gross motor milestones.
• [8] Cerebellar ataxia (staggering gait and imbalance) may develop later. Delayed acquisition of motor milestones is common.

Diagnostic Tests for Joubert Syndrome 28

Joubert Syndrome 28 (JS28) is a rare genetic disorder characterized by cerebellar ataxia, oculomotor apraxia, hypotonia, neonatal breathing issues, and psychomotor delay. Diagnostic tests play a crucial role in confirming the diagnosis of JS28.

• Molecular Genetics Tests: These tests can detect sequence variations in the AHI1 gene, which is associated with Joubert Syndrome 28 [6]. The tests include deletion/duplication analysis, sequence analysis of select exons, targeted variant analysis, and sequence analysis of the entire gene.
• Imaging Studies: Magnetic Resonance Imaging (MRI) and ultrasonography (US) are essential for diagnosing JS28. These imaging studies can reveal characteristic brain malformations and other CNS defects [7].
• Clinical Examination: A thorough clinical examination is necessary to identify characteristic features of JS28, such as hypotonia, abnormal ocular movements, and neonatal respiratory issues.
• Genetic Testing: Genetic testing may include a G-banded chromosome study, which can reveal chromosomal abnormalities associated with Joubert Syndrome 28 [5].

References:

[1] Molecular Genetics Tests · Deletion/duplication analysis (22) · Sequence analysis of select exons (1) · Targeted variant analysis (9) · Sequence analysis of the ...

[2] by M Parisi · 2017 · Cited by 128 — Diagnosis/testing. The clinical diagnosis of JS is based on the presence of characteristic clinical features and MRI findings.

[3] Jul 1, 2017 — 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 ...

[4] Aug 28, 2020 — The diagnosis for JS is established by a combination of: Clinical examination and imaging studies of the midbrain and pons that resemble the characteristic ...

[5] by MA Parisi · 2007 · Cited by 338 — Genetic testing may include a G-banded chromosome study, as part of

Medications Used in Joubert Syndrome

While there is no definitive treatment available for Joubert syndrome, medications may be used to manage specific symptoms and manifestations.

• Seizure control: Medications such as anticonvulsants may be prescribed to control seizures in individuals with Joubert syndrome.
• Behavioral problems: Medications like mood stabilizers or antidepressants may be used to manage behavioral problems associated with the condition.
• Respiratory issues: Stimulatory medications may be required for infants and children with abnormal breathing patterns.

Important Considerations

• Non-steroidal anti-inflammatory drugs (NSAIDs) should be used with caution, as they can exacerbate kidney or liver impairment in individuals with Joubert syndrome.
• Nephrotoxic medications should be avoided in those with renal impairment, while hepatotoxic drugs should be avoided in those with liver impairment.

Multidisciplinary Approach

Management of Joubert syndrome typically involves a multidisciplinary approach, including physical therapy, occupational therapy, speech therapy, and other supportive care measures. A healthcare provider can provide personalized guidance on the best course of treatment for an individual with Joubert syndrome.

References: [8] [9] [14]

Differential Diagnosis of Joubert Syndrome

Joubert syndrome, a rare autosomal recessive disorder, requires careful differential diagnosis to rule out other conditions that may present with similar symptoms. The following are some of the key conditions to consider in the differential diagnosis of Joubert syndrome:

• Cerebellar vermis malformations without the Molar Tooth Sign (e.g., Dandy-Walker): This condition can present with similar cerebellar and brainstem abnormalities, but without the characteristic molar tooth sign.
• Laurence-Moon-Biedl syndrome: This condition shares some similarities in presentation with Joubert syndrome, including developmental delays and hypotonia. However, it is a distinct entity with its own set of clinical features.
• Other ciliopathies (e.g., nephronophthisis and Senior-Loken syndrome): These conditions are characterized by mid-hindbrain malformation, developmental delay, and other systemic features that may overlap with Joubert syndrome.
• Distinct cerebellar and brainstem congenital defects: Certain congenital anomalies of the cerebellum and brainstem can present with similar symptoms to Joubert syndrome.

Key Features to Consider

When considering differential diagnosis for Joubert syndrome, it is essential to look out for the following features:

• Cerebellar and brainstem malformation: The presence of a molar tooth sign or other cerebellar and brainstem abnormalities can help differentiate Joubert syndrome from other conditions.
• Developmental delay and hypotonia: These symptoms are common in Joubert syndrome, but may also be present in other ciliopathies or congenital anomalies.
• Breathing abnormalities: Episodic tachypnea or apnea and/or atypical eye movements can help differentiate Joubert syndrome from other conditions.

References

[8] Romani, M. (2013). Clinical differential diagnosis of Joubert syndrome and related disorders. [Cited by 411]

[10] Joubert Syndrome is a congenital condition with a triad of major findings: global developmental delay, hypotonia in infancy, and pathognomonic cerebellar and brainstem malformation (aplasia or hypoplasia of cerebellar vermis). [Cited by 11]

[13] Classic Joubert syndrome (JS) is characterized by three primary findings: A distinctive cerebellar and brain stem malformation called the molar tooth sign (MTS), Hypotonia, Developmental delays. Often these findings are accompanied by episodic tachypnea or apnea and/or atypical eye movements. [Cited by 14]