Macrocephaly-capillary malformation

Macrocephaly-capillary malformation
Synonyms	Macrocephaly-cutis marmorata telangiectatica congenita syndrome, Megalencephaly-cutis marmorata telangiectatica congenita syndrome, M-CM syndrome, MCAP
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Field	Medical genetics, Pediatrics, Neurology
Symptoms	Macrocephaly, capillary malformations, developmental delay, hypotonia, connective tissue abnormalities, asymmetry, brain overgrowth, polymicrogyria, syndactyly
Complications	Seizures, intellectual disability, overgrowth syndromes, risk of hydrocephalus
Onset	Congenital
Duration	Lifelong
Types	Overgrowth syndrome
Causes	Somatic mutations in the PIK3CA gene
Risks	Sporadic; not usually inherited
Diagnosis	Clinical examination, MRI, genetic testing
Differential diagnosis	Klippel–Trénaunay syndrome, Proteus syndrome, Sturge–Weber syndrome, other PIK3CA-related overgrowth spectrum conditions
Prevention	None
Treatment	Supportive and symptomatic; includes physical therapy, occupational therapy, seizure management
Medication	Anticonvulsants for seizures; investigational targeted therapies (e.g. PI3K inhibitors)
Prognosis	Variable; depends on severity of symptoms and complications
Frequency	Rare; estimated fewer than 1 in 1,000,000 live births
Deaths	Rare; typically related to neurological complications

Macrocephaly-capillary malformation (M-CM) is a rare genetic disorder characterized by a combination of macrocephaly, capillary malformation, and other distinctive features. It is also known as macrocephaly-capillary malformation syndrome (M-CM syndrome) or macrocephaly-cutis marmorata telangiectatica congenita (M-CMTC).

Clinical Features

Individuals with M-CM typically present with a range of clinical features, which may vary in severity. The hallmark features include:

• Macrocephaly: An abnormally large head size, often present at birth or developing in early infancy.
• Capillary malformations: These are flat, pink or red birthmarks, often referred to as "port-wine stains," that can occur anywhere on the body.
• Overgrowth: Disproportionate overgrowth of one side of the body (hemihyperplasia) or generalized overgrowth.
• Developmental delay: Many individuals experience delays in reaching developmental milestones.
• Hypotonia: Decreased muscle tone, which can affect motor skills.
• Syndactyly: Fusion of fingers or toes, which may be partial or complete.
• Polydactyly: Extra fingers or toes.
• Connective tissue abnormalities: Such as joint hypermobility or skin laxity.

Genetics

M-CM is caused by mutations in the PIK3CA gene, which plays a role in cell growth and division. These mutations are typically not inherited but occur as a de novo event, meaning they arise spontaneously in the affected individual. The condition is part of a group of disorders known as PIK3CA-related overgrowth spectrum (PROS).

Diagnosis

Diagnosis of M-CM is based on clinical evaluation and the presence of characteristic features. Genetic testing can confirm the diagnosis by identifying mutations in the PIK3CA gene. Imaging studies, such as MRI or CT scan, may be used to assess brain structure and identify any associated abnormalities.

Management

There is no cure for M-CM, and treatment is symptomatic and supportive. Management may involve:

• Regular monitoring of head growth and development.
• Physical and occupational therapy to address motor delays and hypotonia.
• Surgical intervention for syndactyly or polydactyly if necessary.
• Educational support for developmental delays.
• Monitoring for potential complications, such as seizures or hydrocephalus.

Prognosis

The prognosis for individuals with M-CM varies depending on the severity of symptoms and associated complications. Early intervention and supportive therapies can improve quality of life and developmental outcomes.

Related pages

• Genetic disorder
• Overgrowth syndrome
• PIK3CA-related overgrowth spectrum
• Capillary malformation

External links

• Genetics Home Reference