Rare Gastroenterology News

Disease Profile

TARP syndrome

Prevalence
Prevalence estimates on Rare Medical Network websites are calculated based on data available from numerous sources, including US and European government statistics, the NIH, Orphanet, and published epidemiologic studies. Rare disease population data is recognized to be highly variable, and based on a wide variety of source data and methodologies, so the prevalence data on this site should be assumed to be estimated and cannot be considered to be absolutely correct.
<1 / 1 000 000

< 331

US Estimated

< 514

Europe Estimated

Age of onset

Antenatal

ICD-10

Q87.8

Inheritance

Autosomal dominant A pathogenic variant in only one gene copy in each cell is sufficient to cause an autosomal dominant disease

no.svg

Autosomal recessive Pathogenic variants in both copies of each gene of the chromosome are needed to cause an autosomal recessive disease and observe the mutant phenotype

no.svg

X-linked
dominant X-linked dominant inheritance, sometimes referred to as X-linked dominance, is a mode of genetic inheritance by which a dominant gene is carried on the X chromosome.

no.svg

X-linked
recessive Pathogenic variants in both copies of a gene on the X chromosome cause an X-linked recessive disorder

no.svg

Mitochondrial or multigenic Mitochondrial genetic disorders can be caused by changes (mutations) in either the mitochondrial DNA or nuclear DNA that lead to dysfunction of the mitochondria and inadequate production of energy.

no.svg

Multigenic or multifactor Inheritance involving many factors, of which at least one is genetic but none is of overwhelming importance, as in the causation of a disease by multiple genetic and environmental factors.

no.svg

Not applicable

no.svg

Other names (AKA)

Talipes equinovarus, atrial septal defect, robin sequence, and persistence of left superior vena cava; TARPS; Pierre Robin syndrome with congenital heart malformation and clubfoot;

Categories

Congenital and Genetic Diseases; Ear, Nose, and Throat Diseases; Heart Diseases;

Summary

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]

Symptoms

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

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]

This table lists symptoms that people with this disease may have. For most diseases, symptoms will vary from person to person. People with the same disease may not have all the symptoms listed. This information comes from a database called the Human Phenotype Ontology (HPO) . The HPO collects information on symptoms that have been described in medical resources. The HPO is updated regularly. Use the HPO ID to access more in-depth information about a symptom.

Medical Terms Other Names
Learn More:
HPO ID
80%-99% of people have these symptoms
Atrial septal defect
An opening in the wall separating the top two chambers of the heart
Hole in heart wall separating two upper heart chambers

[ more ]

0001631
Persistent left superior vena cava
0005301
Pierre-Robin sequence
0000201
Talipes equinovarus
Club feet
Club foot
Clubfeet
Clubfoot

[ more ]

0001762
30%-79% of people have these symptoms
Cleft palate
Cleft roof of mouth
0000175
Cyanosis
Blue discoloration of the skin
0000961
Failure to thrive
Faltering weight
Weight faltering

[ more ]

0001508
Generalized hypotonia
Decreased muscle tone
Low muscle tone

[ more ]

0001290
Global developmental delay
0001263
Glossoptosis
Retraction of the tongue
0000162
Hypertelorism
Wide-set eyes
Widely spaced eyes

[ more ]

0000316
Intellectual disability
Mental deficiency
Mental retardation
Mental retardation, nonspecific
Mental-retardation

[ more ]

0001249
Intrauterine growth retardation
Prenatal growth deficiency
Prenatal growth retardation

[ more ]

0001511
Micrognathia
Little lower jaw
Small jaw
Small lower jaw

[ more ]

0000347
Rocker bottom foot
Rocker bottom feet
Rocker-bottom feet
Rockerbottom feet

[ more ]

0001838
Sloping forehead
Inclined forehead
Receding forehead

[ more ]

0000340
Underdeveloped supraorbital ridges
Flattened bony protrusion above eyes
0009891
Wide nasal bridge
Broad nasal bridge
Broad nasal root
Broadened nasal bridge
Increased breadth of bridge of nose
Increased breadth of nasal bridge
Increased width of bridge of nose
Increased width of nasal bridge
Nasal bridge broad
Wide bridge of nose
Widened nasal bridge

[ more ]

0000431
5%-29% of people have these symptoms
Abnormal corpus callosum morphology
0001273
Anteverted nares
Nasal tip, upturned
Upturned nasal tip
Upturned nose
Upturned nostrils

[ more ]

0000463
Apnea
0002104
Broad-based gait
Wide based walk
0002136
Cerebellar hypoplasia
Small cerebellum
Underdeveloped cerebellum

[ more ]

0001321
Clinodactyly
Permanent curving of the finger
0030084
Cryptorchidism
Undescended testes
Undescended testis

[ more ]

0000028
Extramedullary hematopoiesis
0001978
Finger syndactyly
0006101
Hand polydactyly
Extra finger
0001161
Hearing impairment
Deafness
Hearing defect

[ more ]

0000365
Horseshoe kidney
Horseshoe kidneys
0000085
Hydronephrosis
0000126
Hypoplasia of proximal radius
0006434
Low-set, posteriorly rotated ears
0000368
Myopia
Close sighted
Near sighted
Near sightedness
Nearsightedness

[ more ]

0000545
Optic atrophy
0000648
Pectus excavatum
Funnel chest
0000767
Postaxial polydactyly
0100259
Prominent antihelix
0000395
Scoliosis
0002650
Seizure
0001250
Short palpebral fissure
Short opening between the eyelids
0012745
Short sternum
0000879
Single transverse palmar crease
0000954
Small earlobe
Small earlobes
0000385
Tetralogy of Fallot
0001636
Thick eyebrow
Bushy eyebrows
Dense eyebrow
Heavy eyebrows
Prominent eyebrows
Thick eyebrows

[ more ]

0000574
Tongue nodules
0000199
Widely patent fontanelles and sutures
0004492
1%-4% of people have these symptoms
Abnormal duodenum morphology
0002246
Abnormal hair pattern
Abnormal distribution of hair
0010720
Alveolar ridge overgrowth
Overgrowth of gum ridge

Cause

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]

Diagnosis

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.

Testing Resources

  • The Genetic Testing Registry (GTR) provides information about the genetic tests for this condition. The intended audience for the GTR is health care providers and researchers. Patients and consumers with specific questions about a genetic test should contact a health care provider or a genetics professional.

    Organizations

    Support and advocacy groups can help you connect with other patients and families, and they can provide valuable services. Many develop patient-centered information and are the driving force behind research for better treatments and possible cures. They can direct you to research, resources, and services. Many organizations also have experts who serve as medical advisors or provide lists of doctors/clinics. Visit the group’s website or contact them to learn about the services they offer. Inclusion on this list is not an endorsement by GARD.

    Organizations Supporting this Disease

      Learn more

      These resources provide more information about this condition or associated symptoms. The in-depth resources contain medical and scientific language that may be hard to understand. You may want to review these resources with a medical professional.

      In-Depth Information

      • The Monarch Initiative brings together data about this condition from humans and other species to help physicians and biomedical researchers. Monarch’s tools are designed to make it easier to compare the signs and symptoms (phenotypes) of different diseases and discover common features. This initiative is a collaboration between several academic institutions across the world and is funded by the National Institutes of Health. Visit the website to explore the biology of this condition.
      • Online Mendelian Inheritance in Man (OMIM) is a catalog of human genes and genetic disorders. Each entry has a summary of related medical articles. It is meant for health care professionals and researchers. OMIM is maintained by Johns Hopkins University School of Medicine. 
      • Orphanet is a European reference portal for information on rare diseases and orphan drugs. Access to this database is free of charge.
      • PubMed is a searchable database of medical literature and lists journal articles that discuss TARP syndrome. Click on the link to view a sample search on this topic.

        References

        1. Campbell, RM. Femoral Hypoplasia-Unusual Facies Syndrome, NORD Guide to Rare Disorders. Philadelphia: Lippincott Williams & Wilkins; 2003;
        2. Johnston JJ, Teer JK, Cherukuri PF, Hansen NF, Loftus SK; NIH Intramural Sequencing Center (NISC), Chong K, Mullikin JC, Biesecker LG. Massively parallel sequencing of exons on the X chromosome identifies RBM10 as the gene that causes a syndromic form of cleft palate. Am J Hum Genet. 2010; 86(5):743-748. https://www.ncbi.nlm.nih.gov/pubmed/20451169.
        3. Johnston JJ. et. al. Expansion of the TARP syndrome phenotype associated with de novo mutations and mosaicism. Am J Med Genet A. November 20, 2013; Epub ahead of print:Accessed 12/5/2013.
        4. Gripp KW, Hopkins E, Johnston JJ, Krause C, Dobyns WB, Biesecker LG. Long-term survival in TARP syndrome and confirmation of RBM10 as the disease-causing gene. Am J Med Genet A. October 2011; 155A(10):2516-2520. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3183328/. Accessed 12/5/2013.
        5. Ingrid M. Wentzensen. TARP syndrome; TARPS. OMIM. June 19, 2014; https://omim.org/entry/311900.

        Rare Gastroenterology News