Mandibuloacral dysplasia
Mandibuloacral dysplasia is a condition characterized by abnormalities in bone development, skin pigmentation, and fat distribution.
Overview
Mandibuloacral dysplasia causes a variety of physical abnormalities. Affected individuals may experience slow growth after birth and are often born with an underdeveloped lower jaw bone (mandible) and small collar bones (clavicles), resulting in a small chin and sloped shoulders. Other skeletal issues include loss of bone from the tips of the fingers (acroosteolysis), delayed closure of skull bones, and joint deformities (contractures).
Skin abnormalities, such as mottled or patchy pigmentation, are common. Some individuals exhibit features of premature aging (progeria), including thin skin, hair loss, tooth loss, and a beaked nose. Metabolic problems, such as diabetes, may also occur.
Lipodystrophy
A common feature is a lack of fatty tissue under the skin (lipodystrophy). The condition is divided into two types based on fat distribution:
- Type A (MADA): Partial lipodystrophy; loss of fatty tissue from the torso and limbs, with potential buildup around the neck and shoulders.
- Type B (MADB): Generalized lipodystrophy; loss of fatty tissue in the face, torso, and limbs.
Causes
The two forms are caused by mutations in different genes involved in maintaining the structure of the nuclear envelope:
- LMNA gene: Mutations cause MADA. This gene provides instructions for making lamin A and lamin C proteins, which act as scaffolding for the nuclear envelope.
- ZMPSTE24 gene: Mutations cause MADB. This gene is involved in processing immature lamin A into mature lamin A. Mutations lead to a buildup of the immature protein and a shortage of the mature version.
Inheritance
Mandibuloacral dysplasia is inherited in an autosomal recessive pattern, meaning both copies of the gene in each cell have mutations. Parents of an affected individual each carry one copy of the mutated gene but typically do not show symptoms.
