Tetra-amelia syndrome

Tetra-amelia syndrome (tetra- + amelia), also called autosomal recessive tetraamelia,[1] is an extremely rare autosomal recessive[2] congenital disorder characterized by the absence of all four limbs. Other areas of the body are also affected by malformations, such as the face, skull, reproductive organs, anus, lungs and pelvis.[1] The disorder can be caused by recessive mutations in the WNT3 or RSPO2 genes.[2][3]

Tetra-amelia syndrome
Other namesAutosomal recessive tetraamelia
Violetta, a 1920s sideshow performer with tetra-amelia syndrome

Presentation

Tetra-amelia syndrome is characterized by the complete absence of all four limbs. The syndrome causes severe malformations of various parts of the body, including the face and head, heart, nervous system, skeleton, and genitalia.[1] In many cases, the lungs are underdeveloped, which makes breathing difficult or impossible. Because children with tetra-amelia syndrome have such serious medical problems, most are stillborn or die shortly after birth.

Cause
Tetra-amelia syndrome has an autosomal recessive pattern of inheritance.

RSPO2 and WNT3 genes

Researchers have found loss-of-function mutations in the WNT3 or the RSPO2 genes in people with tetra-amelia syndrome from several consanguineous families. These two gene encode proteins belonging to the WNT pathway which plays critical roles during development.

The protein produced from the WNT3 and RSPO2 genes are involved in the formation of the limbs and other body systems during embryonic development. Mutations in the WNT3 or RSPO2 genes prevent cells from producing functional WNT3 and RSPO2 proteins, which disrupts normal limb formation and leads to the other serious birth defects associated with tetra-amelia syndrome.

According to a 2018 study by Bruno Reversade, the loss of RSPO2, unlike WNT3, also prevents formation of the lungs causing a lethal syndrome of tetra-amelia.[3]

Inheritance within families

In most of the families reported so far, tetra-amelia syndrome appears to have an autosomal recessive pattern of inheritance.[1][2] This means the defective gene responsible for the disorder is located on an autosome , and two copies of the defective gene (one inherited from each parent) are required in order to be born with the disorder. The parents of an individual with an autosomal recessive disorder both carry one copy of the defective gene, but usually do not experience any signs or symptoms of the disorder.

Epidemiology

Tetra-amelia syndrome has been reported in only a few families worldwide. According to a 2011 study by Bermejo-Sanchez, amelia – that is, the lacking of one or more limbs – occurs in roughly 1 out of every 71,000 pregnancies.[1]

People with tetra-amelia syndrome
Nick Vujicic, a motivational speaker who was born with tetra-amelia syndrome, speaking during the session "Inspired for a Lifetime" at the Annual Meeting 2011 of the World Economic Forum in Davos, Switzerland, on 30 January 2011 [4][5]
  • Joanne O'Riordan of Millstreet, Cork, Ireland. At the age of 16 she addressed the United Nations in New York. She appeared before the International Telecommunication Union’s conference ‘Girls in Technology’, receiving a standing ovation after delivering the keynote speech.
  • Hirotada Ototake
  • Nick Vujicic, founder of Life Without Limbs.[6]
  • Prince Randian
  • Violetta (entertainer)
  • Kent Bell (1965-2015) of Jacksonville, FL, scoreboard operator and disabled rights advocate, appeared on Oprah Winfrey show and in numerous print articles over the course of his life.
  • Rob Mendez, varsity football team offensive coordinator at Francis Parker School (San Diego).[7]
  • Christian Arndt of Germany, media presenter.

References
  1. Online Mendelian Inheritance in Man (OMIM): 273395
  2. Niemann, S.; Zhao, C.; Pascu, F.; Stahl, U.; Aulepp, U.; Niswander, L.; Weber, J.; Muller, U. (Mar 2004). "Homozygous WNT3 Mutation Causes Tetra-Amelia in a Large Consanguineous Family". The American Journal of Human Genetics (Free full text). 74 (3): 558–563. doi:10.1086/382196. PMC 1182269. PMID 14872406.
  3. Szenker-Ravi, Emmanuelle; Altunoglu, Umut; Leushacke, Marc; Bosso-Lefèvre, Célia; Khatoo, Muznah; Thi Tran, Hong; Naert, Thomas; Noelanders, Rivka; Hajamohideen, Amin; Beneteau, Claire; de Sousa, Sergio B. (May 2018). "RSPO2 inhibition of RNF43 and ZNRF3 governs limb development independently of LGR4/5/6". Nature. 557 (7706): 564–569. doi:10.1038/s41586-018-0118-y. ISSN 1476-4687. PMID 29769720.
  4. Overcoming hopelessness | Nick Vujicic | TEDxNoviSad, retrieved 2019-08-15
  5. "TED Prize winner Sugata Mitra to speak at conference in Kuala Lumpur". The Star Online. 2013-11-12. Retrieved 2019-08-15.
  6. VUJICIC, NICK. "Life Without Limbs // Nick Vujicic". Life Without Limbs. Retrieved 2019-07-30.
  7. "San Diego high school football coach born with rare disability sets example for perseverance". 10news.com. Retrieved 2021-10-13.
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