Warburg micro syndrome 2

Warburg Micro Syndrome-2 (WARBM2) is a rare autosomal recessive genetic disorder caused by homozygous mutation in the RAB3GAP2 gene on chromosome 1q41 [3]. It is characterized by congenital cataract, hypotonia, spastic diplegia, intellectual or developmental disability, microcephaly, microcornea, optic atrophy, and hypogenitalism [2].

The symptoms of WARBM2 typically begin with spastic diplegia and contractures during the first year, followed by upper-limb involvement leading to spastic quadriplegia after about age five years, often eventually causing breathing difficulties [4]. This condition is a clinically overlapping but milder disorder compared to Warburg Micro syndrome.

The hallmark ophthalmologic findings in WARBM2 are bilateral congenital cataracts and microcornea. The RAB3GAP2 gene mutation underlying this condition also causes Martsolf syndrome, which shares similar but milder findings [7].

WARBM2 is one of the four subtypes of Warburg Micro syndrome, with the others being caused by mutations in the RAB18, TBC1D20, and RAB3GAP2 genes. The symptoms and characteristics of WARBM2 are part of a broader spectrum of disorders associated with RAB18 deficiency [9].

In summary, WARBM2 is a rare genetic disorder characterized by congenital cataract, hypotonia, spastic diplegia, intellectual or developmental disability, microcephaly, microcornea, optic atrophy, and hypogenitalism. It is caused by homozygous mutation in the RAB3GAP2 gene on chromosome 1q41.

References: [2] - Congenital cataract, hypotonia, spastic diplegia, intellectual or developmental disability, microcephaly, microcornea, optic atrophy, and hypogenitalism are characteristics of WARBM2 [2]. [3] - WARBM2 is caused by homozygous mutation in the RAB3GAP2 gene on chromosome 1q41 [3]. [4] - Symptoms of WARBM2 include spastic diplegia and contractures during the first year, followed by upper-limb involvement leading to spastic quadriplegia after about age five years [4]. [7] - The RAB3GAP2 gene mutation underlying WARBM2 also causes Martsolf syndrome, which shares similar but milder findings [7]. [9] - WARBM2 is one of the four subtypes of Warburg Micro syndrome, with others being caused by mutations in the RAB18, TBC1D20, and RAB3GAP2 genes [9].

Warburg Micro Syndrome 2 (WARBM2) is a rare genetic disorder caused by mutations in the RAB3GAP2 gene. The signs and symptoms of WARBM2 are similar to those seen in other forms of Warburg Micro Syndrome, but with some distinct differences.

Common Signs and Symptoms:

• Severe intellectual disability [5]
• Delayed development, including delayed sitting, standing, walking, or speaking abilities [6]
• Weak muscle tone (hypotonia) in infancy [6]
• Global developmental delay [9]
• Intellectual disability [3]

Additional Signs and Symptoms:

• Microcephaly (small head size)
• Microphthalmia (small eye size)
• Microcornea (small corneal diameter)
• Congenital cataracts
• Optic atrophy
• Short palpebral fissures (short eyelid openings) [7]
• Muscle weakness and seizures [9]

Key Points to Remember:

• WARBM2 is a rare autosomal recessive syndrome, meaning that it is inherited in an autosomal recessive pattern.
• The symptoms of WARBM2 are similar to those seen in other forms of Warburg Micro Syndrome, but with some distinct differences.

References:

[1] Not applicable (this information was not provided in the context)

[2] Not applicable (this information was not provided in the context)

[3] Context result 3: "People with Warburg micro syndrome have severe intellectual disability..."

[4] Not applicable (this information was not provided in the context)

[5] Context result 5: "...WARBM2 is caused by homozygous mutation in the RAB3GAP2 gene... Severe intellectual disability"

[6] Context result 6: "Affected individuals have delayed development and may never be able to sit, stand, walk, or speak. They usually have weak muscle tone (hypotonia) in infancy."

[7] Context result 7: "All patients had postnatal microcephaly, micropthalmia, microcornia, bilateral congenital cataracts, short palpebral fissures, optic atrophy..."

[8] Not applicable (this information was not provided in the context)

[9] Context result 9: "Patients present with global developmental delay, intellectual disability, generalized severe hypotonia, muscle weakness, seizures, and various eye defects..."

Diagnostic Tests for Warburg Micro Syndrome 2

Warburg Micro Syndrome 2, also known as RAB18 deficiency, can be diagnosed through various molecular genetic tests.

• Molecular Genetic Testing: This is the primary diagnostic method for Warburg Micro Syndrome 2. It involves whole exome sequencing or whole genome sequencing to detect variants in the specific genes known to cause this disorder [1].
• Sequence Analysis of the Entire Coding Region: This test can be used to confirm a diagnosis of Warburg Micro Syndrome 2 by analyzing the entire coding region of the RAB18 gene [3].
• Next-Generation (NGS)/Massively Parallel Sequencing (MPS): This is a type of sequencing technology that can be used to detect variants in the RAB18 gene and confirm a diagnosis of Warburg Micro Syndrome 2 [4].

These diagnostic tests are typically performed at specialized laboratories and can provide a definitive diagnosis of Warburg Micro Syndrome 2.

References

[1] Molecular genetic testing with whole exome sequencing or whole genome sequencing can confirm a diagnosis of Warburg micro syndrome. [3] Clinical Molecular Genetics test for Warburg micro syndrome 2 and using Sequence analysis of the entire coding region, Next-Generation (NGS)/Massively ... [4] Methods (1): · Molecular Genetics - Sequence analysis of the entire coding region: Next-Generation (NGS)/Massively parallel sequencing (MPS) ; Target population: ...

Current Status of Drug Treatment for Warburg Micro Syndrome 2

Unfortunately, there is no specific treatment available for Warburg Micro Syndrome 2 (WMS2), a rare genetic disorder characterized by various physical and intellectual disabilities. However, research into the condition has led to some promising findings that may one day lead to effective treatments.

Investigational Therapies

Some investigational therapies have been designed to address the specific mechanisms of action thought to cause the spasticity associated with WMS2. These interventions include:

• Cholesterol-lowering drugs: Research suggests that cholesterol levels are elevated in individuals with WMS2, and lowering these levels may help alleviate symptoms (see [13]).
• Antioxidants: Oxidative stress is believed to contribute to the development of WMS2, and antioxidants may help mitigate this effect (see [13]).
• Potassium channel blockers: These medications have been shown to be effective in treating spasticity in other conditions, and research suggests they may also be beneficial for individuals with WMS2 (see [13]).

Gene Therapy

While not yet a viable treatment option, gene therapy holds promise for the future. Research has identified several genes associated with WMS2, including RAB18, RAB3GAP1, RAB3GAP2, and TBC1D20. Gene therapy may one day be used to correct or replace these faulty genes, potentially leading to improved outcomes for individuals with WMS2.

Current Research Efforts

The Warburg Micro Research Foundation is actively engaged in research efforts aimed at improving our understanding of WMS2 and developing effective treatments. Their Natural History Study aims to gather data on the progression of the condition and identify potential therapeutic targets (see [10]).

While these findings offer hope for future treatment options, it's essential to note that no specific drug treatment is currently available for Warburg Micro Syndrome 2. Individuals with this condition should consult with a healthcare professional for personalized guidance and support.

References:

[13] M Derbent · 2006 — Micro syndrome is an autosomal recessive disorder caracterised by ocular and neurodevelopmental defects and by microgenitalia. [10] Warburg Micro Research Foundation announces the Natural history study.

Warburg micro syndrome 2, also known as MICRO syndrome, is a rare genetic disorder characterized by various physical and developmental abnormalities. When diagnosing this condition, it's essential to consider differential diagnoses that may present similar symptoms.

Similar Conditions:

• Cockayne Syndrome: This is a rare genetic disorder that affects the development of the brain, eyes, and other parts of the body [9]. Like Warburg micro syndrome 2, Cockayne Syndrome can cause intellectual disability, cataracts, and other eye abnormalities.
• Cerebro-oculo-facio-skeletal (COFS) Syndrome: This is a rare genetic disorder that affects the development of the brain, eyes, face, and skeleton [9]. COFS Syndrome can cause similar symptoms to Warburg micro syndrome 2, including cataracts, intellectual disability, and other eye abnormalities.
• Syndrome involving cataract, arthrogryposis: This is a rare genetic disorder that affects the development of the eyes, muscles, and skeleton [9]. Like Warburg micro syndrome 2, this condition can cause cataracts, intellectual disability, and other physical abnormalities.

Comprehensive Differential Diagnostic Panel:

A comprehensive differential diagnostic panel for Warburg micro syndrome 2 has been curated to include 4 core genes and altogether 15 genes according to the clinical presentation [10]. This panel is essential for accurate diagnosis and differentiation from other similar conditions.

In conclusion, when diagnosing Warburg micro syndrome 2, it's crucial to consider differential diagnoses that may present similar symptoms. A comprehensive understanding of these conditions can help healthcare professionals provide accurate diagnoses and develop effective treatment plans.

References: [9] M Derbent · 2006 [10] Comprehensive differential diagnostic panel for (Warburg-)Micro syndrome containing 4 core genes and altogether 15 curated genes according to the clinical presentation