Macrocephaly-capillary malformation (M-CM) is a multiple malformation syndrome causing body and head overgrowth and abnormalities of the skin, vascular system, brain and limbs. The disorder has recently (June 2012) been attributed to a genetic mutation in a gene called PIK3CA. The mutation in M-CM is thought to always occur after cell division begins and is therefore very unlikely to be inherited. A mutation that happens at this stage results in different percentages of cells being affected in different individuals, so there is significant variability in how severely each individual is affected.
Information courtesy of M-CM Network. (See for more information) Resource: http://www.m-cm.net/
CHARACTERISTICS OF M-CM
A key sign of M-CM is progressive brain overgrowth, resulting in macrocephaly (larger than normal head). Complications from brain overgrowth can include hydrocephalus and/ or brain stem compression. Additionally, a variety of brain abnormalities are sometimes seen in M-CM patients.
Other common characteristics of M-CM include body asymmetry (hemihypertrophy or hemihyperplasia), vascular birthmarks that cover a significant portion of the body at birth, doughy skin, hypermobile joints, finger and/or toe polydactyly (extra digits) or syndactyly (fused digits), wide feet, and distinctive facial features. Many children will have a red birthmark on the upper lip at birth. The vascular birthmarks in most individuals will fade over time, distinguishing them from "port-wine stain" birthmarks.
Most affected individuals will have some degree of developmental delay and/or disability.
Not all children with M-CM will have every one of the described problems.
Just like anyone with or without an underlying condition, every patient is different.
The underlying gene for M-CM was identified in 2012, but genetic testing to detect causal mutations requires a type of sequencing that is only available on a research basis. Most cases will be diagnosed by a geneticist based on the observation of characteristics rather than genetic testing. Not all signs listed are required to point to an M-CM diagnosis, and the degree to which individuals are affected varies widely.
PIK3CA, OVERGROWTH AND CANCER
The gene mutations found to cause M-CM occur in a gene called PIK3CA. Several other conditions have recently been found to be caused by mutations in the same gene, and all cause abnormal growth. PIK3CA mutations are also known to make cancerous tumors more aggressive. There may be an elevated risk of cancer in individuals with M-CM. A screening protocol for Wilms’ tumor is recommended for children under 8 years. Caregivers and clinicians should be sensitive to a possible elevated cancer risk in general.
Macrocephaly-capillary malformation syndrome is…
There are approximately 150 documented cases of M-CM worldwide.
M-CM was first documented as a syndrome in 1997. At this time, the vast majority of diagnosed cases are in children. The full natural history of M-CM, particularly how it affects older children and adults, is unknown.
GENETIC AND NON-HEREDITARY
M-CM is usually caused by a mutation that happens after cell division begins, resulting in only a percentage of the body’s cells being affected. This is called somatic mosaicism. The affected gene that causes M-CM is called PIK3CA.
Individuals can be affected in dramatically different degrees. Physical and cognitive disability runs the gamut from very mild to severe.
Specialists required for most patients include neurology, neurosurgery, orthopedics, and genetics. Many patients also require cardiology, ENT, ophthalmology, endocrinology, vascular anomaly specialists, and general surgery. Recommended monitoring includes brain and spine MRI for brain overgrowth complications, as well as abdominal ultrasounds in childhood for kidney tumors.