Macrocephaly-capillary malformation

Medical quality assurance by Dr. Albrecht Nonnenmacher, MD at August 19, 2016
StartDiseasesMacrocephaly-capillary malformation

Macrocephaly-capillary malformation, also referred to as M-CM, is a rare genetic overgrowth syndrome of the skin and other organs. Only recognized within the last several decades, much research remains to understand this complex syndrome. It has been referred to by multiple names, and it may also be called megalencephaly-capillary malformation syndrome (MCAP), which is increasingly becoming the most commonly accepted term for the syndrome.

Contents

Definition & Facts

M-CM is a congenital disorder, meaning that it is present at birth. Most infants and children born with M-CM have an abnormally large head (macrocephaly) or an enlarged brain, as well as capillary malformations which manifest as a lacy pattern on the skin.

M-CM was recognized in 1997 as a distinct disorder. In the years since its recognition, about 150 cases have been reported, but the exact number cannot be determined as some patients are misdiagnosed. Males and females appear to be equally affected.

Symptoms & Complaints

The symptoms, and their severity, of M-CM vary from patient to patient. Some may not exhibit all of the symptoms listed here. Symptoms cluster around abnormalities related to the skin, blood vessels, central nervous system, and limbs.

A great majority of children born with M-CM have an abnormally large head, a condition referred to as macrocephaly, along with an enlarged brain, a condition called megalencephaly. These two symptoms can be observed at birth, and typically the child's head will grow at a faster than usual rate for the first few years of life.

Many also have a birth weight significantly larger than average (fetal macrosomia). Patients may also show signs of asymmetrical growth patterns, which can cause one side of the body to be notably larger than the other. Infants with M-CM often display extensive port-wine stains, which appear as pink to red lacy patches on the trunk, limbs, and face. These birthmarks are capillary malformations caused by abnormal widening of the tiny blood vessels (capillaries) which form a network throughout the human body.

Brain abnormalities present the most serious complications of M-CM, as patients can develop brainstem compression and/or accumulation of excessive cerebrospinal fluid. Children can also show other neurological symptoms, including seizures. Developmental delays occur in nearly all cases.

Limb abnormalities can include extra fingers and toes (polydactyly), webbed fingers and toes (syndactyly), and loose joints. It is important to remember that each individual will exhibit different symptoms. Some complications can become severe, while others may only develop mild symptoms. Families of children with M-CM should work closely with their medical team to seek the best treatment plan.

Causes

There is still need for much research surrounding macrocephaly-capillary malformation. Because it is a newly recognized disorder, the exact cause for M-CM remains unknown, and most cases appear to be random or result from a sporadic mutation. Researchers have determined that the genetic cause for the syndrome is a mutation of gene PIK3CA.

Other overgrowth syndromes are also connected to mutations of this gene, and research is still being done to clarify the connection between different mutations of gene PIK3CA and resulting clinical syndromes. The mutation related to M-CM occurs after cell division begins to create the embryo. This is why there seems to be no familial inheritance of the condition.

Diagnosis & Tests

Diagnosis typically occurs through clinical observation, which requires a full physical examination for M-CM related signs and symptoms. There are no specific tests for M-CM, so diagnosis is done only through evaluation of physical symptom patterns by a medical professional.

Although misdiagnosis and overlooking of symptoms can still occur, increasingly specific diagnostic criteria assists doctors to recognize cases of M-CM early on and ensure the treatment necessary. A continuing lack of consensus about these diagnostic criteria necessitates evaluation by a specialist. A careful evaluation is necessary, as M-CM has similarities to several other rare genetic disorders. Some recent research suggests that diagnosis can be confirmed before birth.

Magnetic resonance imaging (MRI) scans are typically recommended in the diagnosis of M-CM. MRIs are important for children with megalencephaly, or enlarged brains, because of the significant risks of hydrocephalus (fluid on the brain) and cerebellar tonsillar herniation (pressure on the brainstem and spinal cord which blocks the flow of cerebrospinal fluid). Both of these conditions can be developed by children with M-CM and must be monitored. Some doctors may order brain MRIs as often as every six months or more frequently if risk signs for these serious neurological conditions appear.

Some children have elevated risks for certain kinds of cancers due to M-CM. Tests to monitor this risk are highly recommended, including abdominal ultrasounds. There are also risks of cardiac arrhythmias, particularly in early childhood, and echocardiogram or EKG tests may be necessary to evaluate heart conditions.

Treatment & Therapy

There is no cure for macrocephaly-capillary malformation. Because of the range of symptoms related to M-CM, treatment typically includes a wide network of medical and therapeutic specialists. Treatment plans will also vary significantly based on the severity and types of symptoms. These realities continue to reinforce the need for families to work with their medical team to create the best medical action plan for their infant or child.

Developmental delays, which occur almost universally in M-CM patients, can be addressed with the assistance of early intervention and special education programs. Occupational therapy and speech therapy may also be helpful for developmental delays. Physical therapy may be helpful in addressing motor development issues.

Orthopedic surgery may be necessary to address asymmetrical physical development (hemihypertrophy), such as when a child experiences extreme differences in length of limbs. Clearly, the risks of the neurological complications explained above (hydrocephalus and cerebellar tonsillar herniation), necessitate immediate treatment by a neurologist and potentially a neurosurgeon, depending on the severity of the situation. These complications typically develop overtime, so monitoring and treating them will be ongoing. Seizures also must be monitored by a neurologist.

Prevention & Prophylaxis

There does not currently appear to be a way to prevent marocephaly-capillary malformation. The genetic mutations of PIK3CA that cause it cannot be predicted and have no clear familiar link. Genetic testing for M-CM is only currently available for research purposes.