Achondrogenesis

Definition

Definition of Achondrogenesis
Achondrogenesis is a group of severe disorders that affect cartilage and bone development. These conditions are characterized by a small body, short limbs, and other skeletal abnormalities. As a result of serious health problems, infants with achondrogenesis usually die before birth, are stillborn, or die soon after birth from respiratory failure. Some infants, however, have lived for a short time with intensive medical support.

Researchers have described at least three forms of achondrogenesis, designated as type 1A, type 1B, and type 2. The types are distinguished by their signs and symptoms, inheritance pattern, and genetic cause; however, types 1A and 1B are often hard to tell apart without genetic testing.

Achondrogenesis type 1A, which has also been called the Houston-Harris type, is the least well understood of the three forms. Affected infants have extremely short limbs, a narrow chest, short ribs that fracture easily, and soft skull bones. They also lack normal bone formation (ossification) in the spine and pelvis.

Achondrogenesis type 1B, also known as the Parenti-Fraccaro type, is characterized by extremely short limbs, a narrow chest, and a prominent, rounded abdomen. The fingers and toes are short and the feet may be rotated inward. Affected infants frequently have a soft out-pouching around the belly-button (an umbilical hernia) or near the groin (an inguinal hernia).

Infants with achondrogenesis type 2, which is sometimes called the Langer-Saldino type, have short arms and legs, a narrow chest with short ribs, and underdeveloped lungs. This condition is also associated with a lack of ossification in the spine and pelvis. Distinctive facial features include a prominent forehead, a small chin, and, in some cases, an opening in the roof of the mouth (a cleft palate). The abdomen is enlarged, and affected infants often have a condition called hydrops fetalis in which excess fluid builds up in the body before birth.

Symptoms

Symptoms of Achondrogenesis
The list of signs and symptoms for Achondrogenesis includes the 19 symptoms listed below:

1. Short Limbs
2. Narrow Chest
3. Prominent Abdomen
4. Rounded Abdomen
5. Short Fingers
6. Short Toes
7. Inward Rotated Toes
8. Umbilical Hernia
9. Inguinal Hernia
10. Small Chest
11. Short Ribs
12. Underdeveloped Lungs
13. Lack of Spinal Bone Formation
14. Lack of Pelvic Bone Formation
15. Prominent Forehead
16. Small Chin
17. Cleft Palate
18. Large Abdomen
19. Hydrops Fetalis

Causes

Causes of Achondrogenesis
There are various causes of Achondrogenesis

1. Type IA is an autosomal recessive disorder with an unknown chromosomal locus. In the current International Nomenclature of Constitutional Disorders of Bone, type IA is classified under spondylodysplastic and other perinatally lethal groups of osteochondrodysplasias.
2. Type IB is an autosomal recessive disorder resulting from mutations of the diastrophic dysplasia sulfate transporter (DDST) gene (SLC26A2), which is located at 5q32-q33.
3. Type II is an autosomal dominant type II collagenopathy resulting from mutations in the COL2A1 gene, which is located at 12q13.1-q13.3.

Diagnosis

Diagnosis of Achondrogenesis
These resources address the diagnosis or management of achondrogenesis and may include treatment providers.

1. Gene Review: Achondrogenesis Type 1BThis link leads to a site outside Genetics Home Reference.
2. Gene Tests: Achondrogenesis Type IAThis link leads to a site outside Genetics Home Reference.
3. Gene Tests: Sulfate Transporter-Related OsteochondrodysplasiaThis link leads to a site outside Genetics Home Reference.
4. Gene Tests: Type II CollagenopathiesThis link leads to a site outside Genetics Home Reference.
5. MedlinePlus Encyclopedia: Achondrogenesis

Prognosis

Prognosis of Achondrogenesis
The outcome is generally very poor. Many infants with achondrogenesis are stillborn or die shortly after birth because of breathing problems related to the abnormally small chest.

Treatment

Treatment of Achondrogenesis
There is no current therapy. Talk to your doctor about care decisions.

Prevention

Prevention of Achondrogenesis
Based on a few infants with achondrogenesis type 1A, researchers believe that this form of the disorder is inherited in an autosomal recessive pattern. Achondrogenesis type 1B also has an autosomal recessive pattern of inheritance. Autosomal recessive inheritance means both copies of the gene in each cell have mutations. Most often, the parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but do not show signs and symptoms of the condition.

Achondrogenesis type 2 is considered an autosomal dominant disorder because one copy of the altered gene in each cell is sufficient to cause the condition. It is almost always caused by new mutations in the COL2A1 gene and typically occurs in people with no history of the disorder in their family.