SNP Shot: Genomic Insights

Achondrogenesis encompasses a group of severe genetic disorders affecting cartilage and bone development. These conditions lead to a small body size, shortened limbs, and various other skeletal abnormalities. Due to the severity of health complications, infants born with achondrogenesis often die before or shortly after birth due to respiratory failure. In rare instances, infants have survived for a brief period with significant medical intervention.

Researchers have identified at least three distinct forms of achondrogenesis: type 1A, type 1B, and type 2. These types are differentiated by their specific signs and symptoms, their inheritance patterns, and the genes responsible. However, distinguishing between types 1A and 1B can be challenging without genetic analysis.

Achondrogenesis type 1A, also referred to as the Houston-Harris type, is the least understood of the three. Infants with this type display extremely short limbs, a constricted chest, easily fractured short ribs, and impaired bone formation (ossification) in the skull, spine, and pelvis.

Achondrogenesis type 1B, also known as the Parenti-Fraccaro type, is characterized by very short limbs, a narrow chest, and a noticeably large, rounded abdomen. The fingers and toes are short, and the feet may be turned inward and upward, resulting in clubfeet. These infants commonly present with a soft bulge near the belly button (umbilical hernia) or in the groin area (inguinal hernia).

Achondrogenesis type 2, sometimes called the Langer-Saldino type, is marked by short arms and legs, a narrow chest with short ribs, and underdeveloped lungs. It also involves impaired ossification in the spine and pelvis. Characteristic facial features include a prominent forehead, a small chin, and, in some cases, a cleft palate. Affected infants often have an enlarged abdomen and may develop hydrops fetalis, a condition where excess fluid accumulates in the body before birth.

Inheritance:

Achondrogenesis types 1A and 1B are inherited in an autosomal recessive manner. This means that both copies of either the TRIP11 or SLC26A2 gene in each cell must carry mutations for the condition to manifest. Typically, the parents of a child with an autosomal recessive disorder each carry one copy of the mutated gene but do not exhibit any symptoms of the disorder themselves. In contrast, achondrogenesis type 2 is considered an autosomal dominant disorder because only one copy of the altered COL2A1 gene in each cell is enough to cause the condition. It almost always arises from new, spontaneous mutations in the COL2A1 gene and usually occurs in individuals with no prior family history of the disorder.