What are the main distinguishing features between Type 1 and Type 2 tetra-amelia syndrome?

Type 1 tetra-amelia syndrome is typically characterized by severe gastrointestinal issues, such as abdominal wall defects, abnormalities in the diaphragm, and imperforate anus, along with frequent kidney problems like renal agenesis. Type 2 is usually distinguished by the complete absence of both lungs and often includes heart abnormalities.

Can tetra-amelia syndrome be detected during pregnancy, and if so, how?

Yes, tetra-amelia syndrome can often be detected during pregnancy through prenatal ultrasound examinations, which can visualize the absence of limbs and other severe structural abnormalities. Further imaging like fetal MRI may provide additional details.

Is there a known genetic cause for tetra-amelia syndrome, and how is it inherited?

Yes, tetra-amelia syndrome is a genetic disorder. Mutations in certain genes, such as WNT3, have been identified as causes for some cases. It is often inherited in an autosomal recessive pattern, meaning both parents must carry a copy of the mutated gene for their child to be affected, though other genetic causes and sporadic cases can occur. Genetic testing can help identify the specific cause.

What are the typical outcomes for infants diagnosed with tetra-amelia syndrome?

Due to the severe malformations of multiple organ systems, including underdeveloped lungs, most infants with tetra-amelia syndrome are stillborn or die shortly after birth. Survival beyond infancy is extremely rare.

Tetra-amelia syndrome

Tetra-amelia syndrome is a very rare disorder characterized by the absence of all four limbs and severe malformations of other body parts, with two forms distinguished by their specific symptoms and genetic causes.

Overview

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 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 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 kidney problems, such as a lack of kidney development (renal agenesis).

Tetra-amelia syndrome type 2 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 or absence of the , 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).

Frequency

Tetra-amelia syndrome is a very rare condition that has been described in only a few families worldwide. Because this condition is so severe, the frequency is reported to be at least 30 times higher among stillbirths than among live births.

Causes

Variants (also called mutations) in two genes have been found to cause tetra-amelia syndrome. Variants in the WNT3 gene cause tetra-amelia syndrome type 1 and variants in the RSPO2 gene cause tetra-amelia syndrome type 2.

The WNT3 gene is one of a family of genes that are part of a process called Wnt signaling, which is involved in regulating cell growth and development before birth. The protein produced from the WNT3 gene is particularly involved in the formation of the limbs and neurological development.

The RSPO2 gene provides instructions for making a protein called R-spondin-2. The role of this protein is to increase Wnt signaling. Specifically, R-spondin-2, attaches (binds) to certain proteins on the surface of cells to turn off (inactivate) proteins that block Wnt signaling.

The variants in the WNT3 or RSPO2 gene that cause tetra-amelia syndrome likely prevent cells from producing any functional protein. As a result, Wnt signaling is impaired and normal limb formation is disrupted, which leads to the serious birth defects associated with tetra-amelia syndrome types 1 and 2.

In some affected individuals, the cause of tetra-amelia syndrome has not been determined. Researchers believe that unidentified mutations in WNT3, RSPO2, or other genes involved in limb development are probably responsible for the disorder in these cases.

Learn more about the genes associated with Tetra-amelia syndrome

RSPO2
WNT3

Inheritance

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

TETAMS
Tetra-amelia
Tetra-amelia, autosomal recessive