TARP syndrome

What is TARP Syndrome?

TARP syndrome, also known as TARPS (Talipes equinovarus, Atrial septal defect, Robin sequence), is a rare genetic condition that affects males. It is characterized by a combination of birth defects, including:

• Talipes equinovarus: Also known as clubfoot, this is a congenital deformity of the foot where one or both feet are turned inward.
• Atrial septal defect (ASD): A hole in the wall between the heart's two upper chambers, which can lead to heart problems.
• Robin sequence: A rare condition characterized by micrognathia (small lower jaw), cleft palate, and glossoptosis (tongue displacement).

Other associated features

In addition to these classic features, TARP syndrome may also be associated with:

• Developmental delay
• Feeding difficulties
• Congenital heart defects

References:

• [1] - A rare developmental defect during embryogenesis syndrome characterized by Robin sequence (micrognathia, glossoptosis, and cleft palate), atrial septal defect. ([2])
• TARP syndrome is an X-linked syndromic condition including Robin sequence, congenital heart defects, developmental delay, feeding difficulties and ... ([3], [4])
• The classic features of TARP syndrome are talipes equinovarus, atrial septal defect, Robin sequence (micrognathia, cleft palate, and glossoptosis), ... ([6])
• TARP syndrome is a rare condition affecting males that causes several birth defects. TARP stands for Talipes equinovarus, Atrial septal defect, Robin sequence. ([7], [8])

Common Signs and Symptoms of TARP Syndrome

TARP syndrome, also known as Talipes equinovarus, Atrial septal defect, Robin sequence, and Persistent left superior vena cava syndrome, is a rare condition affecting males that causes several birth defects. The classic features of this syndrome include:

• Clubfoot deformity (talipes equinovarus): A congenital deformity of the foot where one or both feet are turned inward or outward.
• Congenital heart defects: Involving failure of the upper heart chambers to close, leading to abnormal heart sounds during a heartbeat (heart murmur) and rapid breathing (tachypnea).
• Robin sequence: A condition characterized by micrognathia (small lower jaw), glossoptosis (tongue displacement), and cleft palate.
• Persistent left superior vena cava: A rare congenital anomaly where the left superior vena cava fails to develop properly.

Other symptoms that may be present in individuals with TARP syndrome include:

• Abnormal heart sound during a heartbeat (heart murmur)
• Rapid breathing (tachypnea)
• Low blood pressure
• Failure to thrive
• Developmental delay

It's essential to note that not all patients have all classic features, and some may experience additional symptoms such as central nervous system dysfunction, renal abnormalities, or variable degrees of thrombocytopenia.

References:

• [1] TARP syndrome is a rare condition affecting males that causes several birth defects. TARP stands for Talipes equinovarus, Atrial septal defect, Robin sequence, and Persistent left superior vena cava. Those with TARP syndrome have clubfoot deformity (talipes equinovarus) and congenital heart defects involving failure of the upper heart chambers to close (atrial septal defect). [6]
• The classic features of TARP syndrome are talipes equinovarus, atrial septal defect, Robin sequence (micrognathia, cleft palate, and glossoptosis), and persistent left superior vena cava. Not all patients have all classic features. Some patients have the additional features of central nervous system dysfunction, renal abnormalities, variable degrees of thrombocytopenia, or other symptoms. [13]
• TARP syndrome is a rare condition affecting males that causes several birth defects. TARP stands for Talipes equinovarus, Atrial septal defect, Robin sequence, and Persistent left superior vena cava. Those with TARP syndrome have clubfoot deformity (talipes equinovarus) and congenital heart defects involving failure of the upper heart chambers to close (atrial septal defect). [12]

Diagnostic Tests for TARP Syndrome

TARP syndrome, a rare developmental defect during embryogenesis syndrome, requires accurate diagnosis to provide appropriate care and management. Several diagnostic tests can help identify the condition.

• Exome Sequencing: This is a comprehensive genetic testing approach that analyzes all protein-coding genes in the genome (exome). Exome sequencing has been shown to be an effective tool for diagnosing individuals with suspected genetic conditions, including TARP syndrome [4].
• Diagnostic Whole-Exome Sequencing: This test involves analyzing the entire coding region of the genome and can identify mutations in the RBM10 gene associated with TARP syndrome [9].
• Sequence Analysis: This test analyzes the entire coding region of the RBM10 gene to detect any mutations that may be causing TARP syndrome. Bi-directional Sanger Sequence Analysis is a type of sequence analysis offered by some laboratories, such as PreventionGenetics and Molecular Diagnostics Lab [11][14].

Other Diagnostic Tests

• Coagulation tests: These tests are not specific to TARP syndrome but can be part of the diagnostic evaluation for patients with bleeding or clotting disorders.
• Imaging studies: Imaging studies, such as X-rays or ultrasounds, may be used to confirm the presence of talipes equinovarus, atrial septal defect, and other physical abnormalities associated with TARP syndrome.

Important Considerations

• A negative test result does not rule out a diagnosis of TARP syndrome since a mutation could be in a region not sequenced or in another gene [12].
• Genetic testing for TARP syndrome is available, including carrier testing. Patients and consumers should consult with a healthcare provider to discuss the risks and benefits of genetic testing [8].

References

[4] by Z Powis · 2017 · Cited by 28 — Diagnostic Exome Sequencing (DES) has been shown to be an effective tool for diagnosis individuals with suspected genetic conditions. [9] by H Daicheng et al. 2022 [11] Clinical Molecular Genetics test for TARP syndrome and using Sequence analysis of the entire coding region, Bi-directional Sanger Sequence Analysis offered by PreventionGenetics. [12] RBM10 is the only gene known to be associated with TARP syndrome. [14] Clinical Molecular Genetics test for TARP syndrome and using Sequence analysis of the entire coding region, Bi-directional Sanger Sequence Analysis offered by Molecular Diagnostics Lab.

Based on the provided context, it appears that there are limited treatment options available for TARP syndrome, and most information focuses on its clinical characteristics rather than specific drug treatments.

However, I found some relevant information in the search results:

• In result 5, it mentions that the FDA has granted accelerated approval for Tarpeyo (budesonide) delayed release capsules to reduce proteinuria (increased protein levels in the urine) in adults. However, there is no direct connection made between this treatment and TARP syndrome.
• Result 10 mentions that Nobias Therapeutics has received rare pediatric disease designation and orphan drug designation for their small-molecule metabotropic glutamate receptor modulator NB-001 for the treatment of a rare disease, but it does not specify TARP syndrome.
• In result 8, there is a case report discussing the use of landiolol for atrial tachyarrhythmia in a patient with tetralogy of Fallot and TARP syndrome. However, this appears to be an isolated case and not a general treatment recommendation.

It's essential to note that these results do not provide conclusive evidence of specific drug treatments for TARP syndrome. The majority of the search results focus on the clinical characteristics and genetic aspects of the condition rather than its treatment.

Based on the available information, it seems that there is limited research or established treatment protocols specifically targeting TARP syndrome. Further investigation would be necessary to determine potential treatment options for this rare condition.

References:

• [5] FDA grants accelerated approval for Tarpeyo (budesonide) delayed release capsules to reduce proteinuria in adults.
• [8] Case report on the use of landiolol for atrial tachyarrhythmia in a patient with tetralogy of Fallot and TARP syndrome.
• [10] Nobias Therapeutics receives rare pediatric disease designation and orphan drug designation for their small-molecule metabotropic glutamate receptor modulator NB-001.

Differential Diagnosis of TARP Syndrome

TARP (Talipes equinovarus, Atrial septal defect, Robin sequence, and Persistence of the left superior vena cava) syndrome is a rare X-linked genetic disorder that can be challenging to diagnose. The differential diagnosis for TARP syndrome includes several other syndromes and conditions that present with similar clinical features.

Key Differential Diagnoses:

• Robin Sequence: A condition characterized by micrognathia, glossoptosis, and cleft palate, which are also hallmarks of TARP syndrome.
• Smith-Lemli-Optz Syndrome: A genetic disorder that presents with a range of clinical features, including developmental delay, feeding difficulties, and congenital heart defects, similar to those seen in TARP syndrome.
• Oro-facial-digital syndrome: A rare genetic disorder characterized by abnormalities of the face, hands, and feet, which can be confused with the physical features of TARP syndrome.

Other Conditions to Consider:

• Congenital Heart Defects: While congenital heart defects are a key feature of TARP syndrome, they can also occur in isolation or as part of other syndromes.
• Developmental Delay and Feeding Difficulties: These symptoms can be seen in a range of conditions, including genetic disorders and neurological impairments.

Importance of Genetic Testing:

In cases where TARP syndrome is suspected, genetic testing for the RBM10 gene mutation is essential to confirm the diagnosis. This can help differentiate TARP syndrome from other syndromes and conditions with similar clinical features.

References:

• [3] Differential diagnoses of TARP syndrome should be made with the Robin sequence, Smith-Lemli-Optz syndrome and oro-facial-digital syndrome.
• [5] genetic diagnosis of TARP syndrome and expansion of the phenotype in a patient with a newly reported RBM10 alteration.
• [9] TARP syndrome (TARPS) is an X-linked syndromic condition including Robin sequence, congenital heart defects, developmental delay, feeding difficulties and talipes equinovarus.