TARP syndrome

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). The Robin sequence (also known as Pierre Robin’s sequence) is characterized by a small lower jaw at birth that prevents proper feeding of the infant, followed by a retracted or displaced tongue. A high-arched, cleft soft palate is also commonly seen.^[1] Affected individuals also have persistent left superior vena cava. TARP syndrome has been reported to cause death before birth or soon after birth. This condition is caused by mutations in the RBM10 gene and is inherited in an X-linked recessive fashion.^[2]

TARP is an acronym for the 4 main features that were present in individuals originally diagnosed with TARP syndrome:

• Talipes equinovarus (clubfoot)
• Atrial septal defect (ASD) - a heart defect at birth characterized by failure of an opening of the upper heart chambers to close
• Robin sequence
• Persistence of the left superior vena cava (SVC).

More recently, some affected individuals (confirmed by genetic testing) have been described having a more diverse range of signs and symptoms. Two boys from one family with TARP syndrome were born without clubfoot, but had additional features including polydactyly (additional fingers and/or toes); cutaneous syndactyly (webbing of the skin between the fingers and/or toes); and masses on the underside of the tongue (sublingual tongue masses). An individual in another family had only one of the 4 main features. An individual in a third family had only 2 of the 4 features of TARP.^[3]

Additional abnormalities that have been reported in the medical literature in affected individuals include failure to thrive; abnormal skull shape; round face; short palpebral fissures (decreased width of each eye); small or abnormally-shaped ears; poor muscle tone (hypotonia); developmental delay; eye or visual abnormalities; hearing loss; airway or lung abnormalities; undescended testicles (cryptorchidism); structural brain abnormalities; and intellectual disability.^[3][4]

Most affected males have died before birth or shortly after birth. However, in 2011 there was a report of an affected individual who was 3 years, 7 months old and was surviving with intensive medical care. The authors of this report concluded that long-term survival is possible for individuals with TARP syndrome and that older affected individuals may exist.^[4]

TARP syndrome is a genetic condition caused by mutations in the RBM10 gene, which is located on the X chromosome. There is little information available about how mutations in this gene specifically cause TARP syndrome. However, in 2010 researchers showed that the RBM10 gene is expressed in mouse embryos in the branchial arches (embryonic structures that give rise to parts of the head and neck) and limbs, which is consistent with body parts known to be affected in individuals with TARP syndrome. The signs and symptoms of TARP syndrome occur when this gene does not function correctly.^[5]

TARP syndrome is inherited in an X-linked recessive manner. This means that the mutated gene responsible for TARP syndrome (RBM10) is located on the X chromosome, and typically only affects males. Males have one X chromosome and one Y chromosome, while females have two X chromosomes. If a female has one mutated copy of RBM10 and one normal copy, she would typically be an unaffected carrier of this condition.

When a female carrier of an X-linked condition has children, each daughter has a 50% (1 in 2) risk to also be a carrier, and a 50% risk to not be a carrier (and have 2 normal copies of the gene). Each son has a 50% risk to be affected and a 50% risk to be unaffected.

Yes, genetic testing (including carrier testing) is available for TARP syndrome. The Genetic Testing Registry (GTR) provides information about the labs that offer genetic testing for this condition. On the GTR Web site, click on the title "Test for TARP syndrome" to find out more information about each test. The intended audience for the GTR is health care providers and researchers. Therefore, patients and consumers with specific questions about a genetic test should contact a health care provider or a genetics professional.

To find a medical professional who specializes in genetics, you can ask your doctor for a referral or you can search for one yourself. Online directories are provided by the American College of Medical Genetics and the National Society of Genetic Counselors. If you need additional help, contact a GARD Information Specialist. You can also learn more about genetic consultations from Genetics Home Reference.