Tetra-amelia syndrome is a very rare disorder characterized by the absence of all four limbs. ("Tetra" is the Greek word for "four," and "amelia" refers to the failure of an arm or leg to develop before birth.) This syndrome can also cause severe malformations of other parts of the body, including the face and head, heart, nervous system, skeleton, and genitalia. The lungs are underdeveloped in many cases, 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.
Tetra-amelia syndrome has been reported in only a few families worldwide.
Researchers have found a mutation in the WNT3 gene in people with tetra-amelia syndrome from one large family. This gene is part of a family of WNT genes that play critical roles in development before birth. The protein produced from the WNT3 gene is involved in the formation of the limbs and other body systems during embryonic development. Mutations in the WNT3 gene prevent cells from producing functional WNT3 protein, which disrupts normal limb formation and leads to the other serious birth defects associated with tetra-amelia syndrome.
In other affected families, the cause of tetra-amelia syndrome has not been determined. Researchers believe that unidentified mutations in WNT3 or other genes involved in limb development are probably responsible for the disorder in these cases.
In most of the families reported so far, tetra-amelia syndrome appears to have an autosomal recessive pattern of inheritance. Autosomal recessive inheritance means both copies of the gene in each cell have mutations. The parents of an individual with tetra-amelia syndrome each carry one copy of the mutated gene, but do not show signs and symptoms of the condition.
Other Names for This Condition
- Tetra-amelia, autosomal recessive
Additional Information & Resources
Genetic Testing Information
Genetic and Rare Diseases Information Center
Catalog of Genes and Diseases from OMIM
Scientific Articles on PubMed
- Başaran S, Yüksel A, Ermiş H, Kuseyri F, Ağan M, Yüksel-Apak M. Tetra-amelia, lung hypo-/aplasia, cleft lip-palate, and heart defect: a new syndrome? Am J Med Genet. 1994 May 15;51(1):77-80. Citation on PubMed
- Gershoni-Baruch R, Drugan A, Bronshtein M, Zimmer EZ. Roberts syndrome or "X-linked amelia"? Am J Med Genet. 1990 Dec;37(4):569-72. Citation on PubMed
- Krahn M, Julia S, Sigaudy S, Liprandi A, Bernard R, Gonnet K, Heuertz S, Bonaventure J, Chau C, Fredouille C, Levy N, Philip N. Tetra-amelia and lung aplasia syndrome: report of a new family and exclusion of candidate genes. Clin Genet. 2005 Dec;68(6):558-60. Citation on PubMed
- Niemann S, Zhao C, Pascu F, Stahl U, Aulepp U, Niswander L, Weber JL, Müller U. Homozygous WNT3 mutation causes tetra-amelia in a large consanguineous family. Am J Hum Genet. 2004 Mar;74(3):558-63. Epub 2004 Feb 5. Citation on PubMed or Free article on PubMed Central
- Ohdo S, Madokoro H, Sonoda T, Takei M, Yasuda H, Mori N. Association of tetra-amelia, ectodermal dysplasia, hypoplastic lacrimal ducts and sacs opening towards the exterior, peculiar face, and developmental retardation. J Med Genet. 1987 Oct;24(10):609-12. Citation on PubMed or Free article on PubMed Central
- Ohdo S, Sonoda T, Ohba K. Natural history and postmortem anatomy of a patient with tetra-amelia, ectodermal dysplasia, peculiar face, and developmental retardation (MIM 273390). J Med Genet. 1994 Dec;31(12):980-1. Citation on PubMed or Free article on PubMed Central
- Rosenak D, Ariel I, Arnon J, Diamant YZ, Ben Chetrit A, Nadjari M, Zilberman R, Yaffe H, Cohen T, Ornoy A. Recurrent tetraamelia and pulmonary hypoplasia with multiple malformations in sibs. Am J Med Genet. 1991 Jan;38(1):25-8. Citation on PubMed
- Zimmer EZ, Taub E, Sova Y, Divon MY, Pery M, Peretz BA. Tetra-amelia with multiple malformations in six male fetuses of one kindred. Eur J Pediatr. 1985 Nov;144(4):412-4. Citation on PubMed
- Zlotogora J, Sagi M, Shabany YO, Jarallah RY. Syndrome of tetraamelia with pulmonary hypoplasia. Am J Med Genet. 1993 Sep 15;47(4):570-1. Citation on PubMed