Microcephaly-capillary malformation syndrome
Microcephaly-capillary malformation syndrome is a rare inherited disorder defined by an abnormally small head size, brain abnormalities, and distinctive skin vascular malformations.
Overview
Microcephaly-capillary malformation syndrome is characterized by an abnormally small head size (microcephaly) and abnormalities of small blood vessels in the skin known as capillary malformations. The condition is rare, with only about a dozen cases diagnosed.
Symptoms
The disorder involves significant neurological and physical challenges:
- Neurological: Microcephaly is present before birth, associated with an unusually small brain and multiple brain abnormalities. Affected individuals experience intractable epilepsy (seizures that are difficult to treat), leading to profound developmental delay and intellectual impairment. Most individuals do not develop skills beyond those of a 1- or 2-month-old infant.
- Skin: Capillary malformations appear as pink or red spots caused by enlarged capillaries. These spots can range from a few to hundreds, appearing anywhere on the body.
- Physical: Other signs include abnormal movements, feeding difficulties, slow growth, short stature, and abnormalities of the fingers and toes (such as hypoplasia or missing nails).
Causes
The syndrome results from mutations in the STAMBP gene, which provides instructions for the STAM binding protein. This protein is involved in sorting damaged or unneeded proteins for degradation or recycling. A shortage of this protein leads to the buildup of cellular waste, which may cause cells to self-destruct (apoptosis). Researchers believe this process, occurring before birth, causes the brain abnormalities and microcephaly associated with the syndrome.
Inheritance
This condition follows an autosomal recessive pattern of inheritance, meaning both copies of the STAMBP gene in each cell have mutations. Typically, an affected individual inherits one altered copy from each parent. In rare instances, an individual may inherit two mutated copies from a single parent due to a genetic error called uniparental disomy.