Megalencephaly-capillary malformation-polymicrogyria

What is megalencephaly-capillary malformation-polymicrogyria?

Megalencephaly-capillary malformation-polymicrogyria (MCAP) was first described in 1997 and is characterised by:

• Macrocephaly (a condition where the head is abnormally large)
• Cutaneous vascular anomalies
• Polymicrogyria (a brain malformation indicated by several small brain convolutions). 

Additional features include varying degrees of asymmetric somatic overgrowth, distal limb malformations, and hyperelasticity. Fewer than 300 cases have been reported in the literature.

MCAP is also known as macrocephaly-capillary malformation (MCM), to reflect large brain size, large head size, and polymicrogyria that characterise the syndrome.

Who gets megalencephaly-capillary malformation-polymicrogyria?

MCAP occurs sporadically and affects boys and girls equally with no ethnic predilections.

What causes megalencephaly-capillary malformation-polymicrogyria?

Some cases of MCAP have been found to have somatic mutations in the phosphatidylinositol-4, 5-bisphosphate 3-kinase catalytic subunit alpha  (PIK3CA) gene on chromosome 3q26.

What are the clinical features of megalencephaly-capillary malformation-polymicrogyria?

These major criteria must both be present for MCAP to be diagnosed:

• Macrocephaly (> 95th percentile) and progressive megalencephaly
• Capillary malformation.

Minor criteria: variable involvement

• Asymmetrical overgrowth
• Developmental delay
• Midline facial capillary malformation
• Neonatal hypotonia
• Syndactyly
• Frontal bossing (rounded prominence of the frontal and parietal bones of the skull)
• Joint hypermobility
• Hyperelastic and/or doughy skin
• Hydrocephalus
• Seizures

How is the diagnosis of megalencephaly-capillary malformation-polymicrogyria made?

Diagnosis of MCAP is made based on clinical signs and neuro-imaging studies. Both major criteria should be present, with variable minor criteria.

Baseline magnetic resonance imaging (MRI) of the brain and spine is recommended at the time of diagnosis.

What is the differential diagnosis for megalencephaly-capillary malformation-polymicrogyria?

MCAP should be distinguished from other overgrowth syndromes with vascular malformations including:

• Cutis marmorata telangiectatica congenita
• Beckwith Weidemann syndrome
• Proteus syndrome
• CLOVES syndrome (congenital, lipomatous, overgrowth, vascular malformations, epidermal nevi and spinal/skeletal anomalies and/or scoliosis)
• PTEN hamartoma tumour syndrome

What is the outcome of megalencephaly-capillary malformation-polymicrogyria?

Patients with MCAP require ongoing medical surveillance as well as physical and occupational therapy. Early intervention is helpful to overcome disability and achieve developmental milestones.

Patients are at increased risk of developing medulloblastoma, meningioma, Wilms tumour and leukaemia over their lifetime. 

In addition to yearly medical exams, all patients should have cardiology consultation at the time of diagnosis.

Follow-up imaging recommendations include:

• MRI of the brain at diagnosis and every 6 months until the age of 2 years
• Serial abdominal sonography every 3–6 months for the first 7 years of life.