Tetra-amelia syndrome also known as tetraamelia-multiple malformations syndrome

Tetra-amelia syndrome (sometimes known as TETAMS) 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 nervous system, face, head, heart, skeleton, gastrointestinal system, urinary tract, 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.

There are two forms of tetra-amelia syndrome

That have been described, and while the features overlap, they are distinguished by their signs and symptoms and genetic cause.

Tetra-amelia syndrome type 1

It is typically characterized by severe gastrointestinal problems. These problems include an opening in the abdomen through which various abdominal organs can protrude (abdominal wall defect), abnormalities in the muscle (diaphragm) that separates the organs in the abdomen from those in the chest, and lack of an anal opening (imperforate anus). People with type 1 also tend to have frequent urinary tract problems, such as a lack of kidney development (renal agenesis).

Tetra-amelia syndrome type 2

It is usually characterized by complete absence of both lungs. Affected individuals often have heart abnormalities, such as defects in the walls between the chambers of the heart (septal defects) or absence of the mitral valve, which connects the two left chambers of the heart. People with type 2 can also have facial abnormalities that include partial or complete fusion of the upper and lower eyelids, the bottom of the tongue attached to the floor of the mouth, or a small lower jaw (micrognathia).

Tetra-amelia syndrome causes

Researchers have found a mutation in the WNT3 gene in people with tetra-amelia syndrome from one large family. The WNT3 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.

Signs and symptoms

Craniofacial

Eyes. Microphthalmia, cataract, microcornea, coloboma, palpebral fusion
Ears. Absence of external ears (microtia), low-set ears
Nose. Single naris, choanal atresia, prominent nose, absence of nose
Mouth. Cleft lip/cleft palate, high and narrow palate, macrostomia, micrognathia

Urogenital

Agenesis of kidney
Rudimentary ovary and salpinx
Persistence of cloaca
Atresia of vagina
Atresia of anus
Atresia of urethra
Hypospadias
Absence of external genitalia
Ambiguous genitalia
Absence of scrotum
Intra-abdominal location of testis

Cardiopulmonary

Hypoplasia/aplasia of lungs, bilobular right lung
Hypoplasia/aplasia of pulmonary vessels
Diaphragmatic defect
Ventricular septal defect
Small right heart
Mitral valve aplasia

Skeletal

Hypoplasia/absence of pelvic bones
Absence of vertebra
Absence of rib

Central nervous system

Agenesis of olfactory nerves
Agenesis of optic nerves
Agenesis of corpus callosum
Hydrocephalus

Other

Polyhydramnios
Absence of nipples
Gastroschisis
Agenesis of suprarenal gland
Agenesis of spleen.

Tetra-amelia syndrome inheritance pattern

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.

It is rare to see any history of autosomal recessive conditions within a family because if someone is a carrier for one of these conditions, they would have to have a child with someone who is also a carrier for the same condition.

Autosomal recessive conditions are individually pretty rare, so the chance that you and your partner are carriers for the same recessive genetic condition are likely low.

Even if both partners are a carrier for the same condition, there is only a 25% chance that they will both pass down the non-working copy of the gene to the baby, thus causing a genetic condition. This chance is the same with each pregnancy, no matter how many children they have with or without the condition.

If both partners are carriers of the same abnormal gene, they may pass on either their normal gene or their abnormal gene to their child. This occurs randomly.
Each child of parents who both carry the same abnormal gene therefore has a 25% (1 in 4) chance of inheriting a abnormal gene from both parents and being affected by the condition.
This also means that there is a 75% ( 3 in 4) chance that a child will not be affected by the condition. This chance remains the same in every pregnancy and is the same for boys or girls.
There is also a 50% (2 in 4) chance that the child will inherit just one copy of the abnormal gene from a parent. If this happens, then they will be healthy carriers like their parents.
Lastly, there is a 25% (1 in 4) chance that the child will inherit both normal copies of the gene. In this case, the child will not have the condition, and will not be a carrier.
These possible outcomes occur randomly. The chance remains the same in every pregnancy and is the same for boys and girls.