SNP Shot: Genomic Insights

Mandibuloacral dysplasia is a disorder characterized by diverse abnormalities affecting bone growth, skin pigmentation, and fat distribution. Individuals with this condition may experience slowed growth after birth. A prominent feature is an underdeveloped lower jaw (mandible) and small collarbones (clavicles), resulting in a small chin and sloped shoulders. Other skeletal issues can include bone loss from the fingertips (acroosteolysis), leading to bulbous fingertips, delayed closure of specific skull bones, and joint deformities (contractures).

Individuals affected by mandibuloacral dysplasia may exhibit uneven skin pigmentation or other skin irregularities. Some individuals display characteristics of premature aging (progeria), such as thin skin, tooth loss, hair loss, and a beaked nose. Furthermore, some individuals with this condition may experience metabolic complications like diabetes.

A hallmark of mandibuloacral dysplasia is the absence of subcutaneous fat (lipodystrophy) in particular areas of the body. The two subtypes, mandibuloacral dysplasia with type A lipodystrophy (MADA) and mandibuloacral dysplasia with type B lipodystrophy (MADB), are differentiated by the pattern of fat loss across the body. Type A involves partial lipodystrophy, where individuals experience fat loss from the trunk and extremities, but potentially increased fat around the neck and shoulders. Type B involves generalized lipodystrophy, with fat loss affecting the face, trunk, and extremities.

MADA typically has an onset in adulthood, although children can also be affected. In contrast, MADB appears earlier, frequently shortly after birth. Many infants with MADB are born prematurely.

Inheritance:

This condition follows an autosomal recessive inheritance pattern. This means that both copies of the relevant gene within each cell possess mutations. The parents of an affected individual each carry a single copy of the mutated gene but usually do not exhibit symptoms of the condition themselves.