Tetra-amelia syndrome (''
tetra-
Numeral or number prefixes are prefixes derived from numerals or occasionally other numbers. In English and many other languages, they are used to coin numerous series of words. For example:
* unicycle, bicycle, tricycle (1-cycle, 2-cycle, 3-cyc ...
'' + ''
amelia''), also called autosomal recessive tetraamelia,
is an extremely rare
autosomal
An autosome is any chromosome that is not a sex chromosome. The members of an autosome pair in a diploid cell have the same morphology, unlike those in allosome, allosomal (sex chromosome) pairs, which may have different structures. The DNA in au ...
recessive
In genetics, dominance is the phenomenon of one variant (allele) of a gene on a chromosome masking or overriding the effect of a different variant of the same gene on the other copy of the chromosome. The first variant is termed dominant and t ...
congenital disorder
A birth defect, also known as a congenital disorder, is an abnormal condition that is present at birth regardless of its cause. Birth defects may result in disabilities that may be physical, intellectual, or developmental. The disabilities can ...
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.
The disorder can be caused by
recessive
In genetics, dominance is the phenomenon of one variant (allele) of a gene on a chromosome masking or overriding the effect of a different variant of the same gene on the other copy of the chromosome. The first variant is termed dominant and t ...
mutations in the
WNT3
Proto-oncogene protein Wnt-3 is a protein that in humans is encoded by the ''WNT3'' gene
In biology, the word gene (from , ; "...Wilhelm Johannsen coined the word gene to describe the Mendelian units of heredity..." meaning ''generation'' o ...
or
RSPO2
R-spondin 2 also known as roof plate-specific spondin-2 is a secreted protein that in humans that is encoded by the ''RSPO2'' gene.
R-spondin 2 synergizes with canonical Wnt signaling pathway, WNT to activate beta-catenin. RSPO2 has been proposed ...
genes.
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.
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
RSPO2 and WNT3 genes
Researchers have found loss-of-function
mutation
In biology, a mutation is an alteration in the nucleic acid sequence of the genome of an organism, virus, or extrachromosomal DNA. Viral genomes contain either DNA or RNA. Mutations result from errors during DNA or viral replication, mi ...
s in the
WNT3
Proto-oncogene protein Wnt-3 is a protein that in humans is encoded by the ''WNT3'' gene
In biology, the word gene (from , ; "...Wilhelm Johannsen coined the word gene to describe the Mendelian units of heredity..." meaning ''generation'' o ...
or the
RSPO2
R-spondin 2 also known as roof plate-specific spondin-2 is a secreted protein that in humans that is encoded by the ''RSPO2'' gene.
R-spondin 2 synergizes with canonical Wnt signaling pathway, WNT to activate beta-catenin. RSPO2 has been proposed ...
genes in people with tetra-amelia syndrome from several
consanguineous
Consanguinity ("blood relation", from Latin '' consanguinitas'') is the characteristic of having a kinship with another person (being descended from a common ancestor).
Many jurisdictions have laws prohibiting people who are related by blood fro ...
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
Bruno Reversade (born 1978) is an American human geneticist and developmental biologist . He is a Director of the Institute of Molecular and Cellular Biology and the Genome Institute of Singapore at A*STAR (Singapore) and holds several faculty ...
, the loss of
RSPO2
R-spondin 2 also known as roof plate-specific spondin-2 is a secreted protein that in humans that is encoded by the ''RSPO2'' gene.
R-spondin 2 synergizes with canonical Wnt signaling pathway, WNT to activate beta-catenin. RSPO2 has been proposed ...
, unlike WNT3, also prevents formation of the lungs causing a lethal syndrome of tetra-amelia.
Inheritance within families
In most of the families reported so far, tetra-amelia syndrome appears to have an
autosomal
An autosome is any chromosome that is not a sex chromosome. The members of an autosome pair in a diploid cell have the same morphology, unlike those in allosome, allosomal (sex chromosome) pairs, which may have different structures. The DNA in au ...
recessive pattern of inheritance.
This means the defective gene responsible for the disorder is located on an
autosome
An autosome is any chromosome that is not a sex chromosome. The members of an autosome pair in a diploid cell have the same morphology, unlike those in allosome, allosomal (sex chromosome) pairs, which may have different structures. The DNA in au ...
, 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
Carry or carrying may refer to:
People
*Carry (name)
Finance
* Carried interest (or carry), the share of profits in an investment fund paid to the fund manager
* Carry (investment), a financial term: the carry of an asset is the gain or cost of h ...
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.
People with tetra-amelia syndrome
*
Joanne O'Riordan
Joanne O'Riordan (born 24 April 1996) is an Irish activist and sports journalist who contributes to ''The Irish Times.'' From Millstreet in County Cork, she is one of seven currently living people born with the condition Tetra-amelia syndrome. ...
of
Millstreet
Millstreet () is a town in north County Cork, Ireland, with a population of 1,555 (as of 2016).
Millstreet is within the civil parish of Drishane, and within a Poor Law Union also called Millstreet. The Millstreet Union encompasses the civil ...
,
Cork
Cork or CORK may refer to:
Materials
* Cork (material), an impermeable buoyant plant product
** Cork (plug), a cylindrical or conical object used to seal a container
***Wine cork
Places Ireland
* Cork (city)
** Metropolitan Cork, also known as G ...
,
Ireland
Ireland ( ; ga, Éire ; Ulster Scots dialect, Ulster-Scots: ) is an island in the Atlantic Ocean, North Atlantic Ocean, in Northwestern Europe, north-western Europe. It is separated from Great Britain to its east by the North Channel (Grea ...
. At the age of 16 she addressed the
United Nations
The United Nations (UN) is an intergovernmental organization whose stated purposes are to maintain international peace and international security, security, develop friendly relations among nations, achieve international cooperation, and be ...
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
(born April 6, 1976) is a Japanese sports writer from Tokyo, Japan.
Born without arms and legs due to a genetic disorder called tetra-amelia syndrome, Ototake is most notable for his 1998 memoir (). Within a year of publication, the book became ...
*
Lisa Manyata Olson Lisa or LISA may refer to:
People
People with the mononym
* Lisa Lisa (born 1967), American actress and lead singer of the Cult Jam
* Lisa (Japanese musician, born 1974), stylized "LISA", Japanese singer and producer
* Lisa Komine (born 1978), J ...
, b. 1974 India. Founder of Manyata Ministries, seeking to share God's message of love and acceptance.
*
Nick Vujicic
Nicholas James Vujicic ( ; born 4 December 1982) is an Australian American Christian evangelist and motivational speaker of Serbian descent, born with tetra-amelia syndrome, a rare disorder characterised by the absence of arms and legs.
Early ...
, founder of Life Without Limbs.
*
Prince Randian
Prince Randian (sometimes misspelled Rardion or Randion; October 12, 1871 – December 19, 1934), also nicknamed Pillow Man, The Snake Man, The Human Torso, The Human Caterpillar and a variety of other names, was a Guyanese-born American per ...
*
Violetta (entertainer)
Aloisia Wagner (born 1905/1906, date of death unknown), better known by her stage name Violetta, was a German-American woman who was born without legs or arms with a condition known as tetra-amelia syndrome. She was born in Hemelingen, Germany, an ...
* 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)
Francis Parker School (''Parker)'' is a college preparatory independent day school in San Diego, California, serving students from junior kindergarten through twelfth grade. Parker was founded in 1912 by Clara Sturges Johnson and William Templeton ...
.
* Christian Arndt of Germany, media presenter.
References
External links
*
{{DEFAULTSORT:Tetra-amelia Syndrome
Congenital disorders
Autosomal recessive disorders
Syndromes
Rare diseases
Extracellular ligand disorders
Congenital amputations