| Macrocephaly-capillary malformation | |
|---|---|
| Classification and external resources | |
| OMIM | 602501 |
| DiseasesDB | 34862 |
Macrocephaly-capillary malformation (M-CM) is a multiple malformation syndrome causing abnormal body and head overgrowth and cutaneous, vascular, neurologic, and limb abnormalities. The disorder is assumed to have a genetic basis, but the precise genetic cause for M-CM is unknown and diagnosis is currently based on clinical observations. Though not every patient has all features, commonly found signs include macrocephaly, congenital macrosomia, extensive cutaneous capillary malformation (naevus flammeus or port-wine stain type birthmark over much of the body; a capillary malformation of the upper lip or philtrum is seen in many patients with this condition), body asymmetry (also called hemihyperplasia or hemihypertrophy), polydactyly or syndactyly of the hands and feet, lax joints, doughy skin, variable developmental delay and other neurologic problems such as seizures and low muscle tone.
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This disorder was recognized as a distinct syndrome in 1997 and named macrocephaly-cutis marmorata telangiectasia congenita or M-CMTC.[1][2] A new name, macrocephaly-capillary malformation, was recommended in 2007.[3] This new name was chosen to more accurately describe the skin markings associated with this disorder.
The genetic cause for M-CM remains unknown, so diagnosis is based on clinical observation. Various sets of criteria have been suggested to identify the disorder in an individual patient, all of which include macrocephaly and a number of the following: somatic overgrowth, cutis marmorata, midline facial birthmark, polydactyly/syndactyly, asymmetry (hemihyperplasia or hemihypertrophy), hypotonia at birth, developmental delay, connective tissue defect and frontal bossing[4][5]. Currently no consensus exists about which diagnostic criteria are definitive and so evaluation by a medical geneticist or other clinician with familiarity with the syndrome is usually needed to provide diagnostic certainty. It is not clear if there are some features which are mandatory to make the diagnosis, but macrocephaly appears essentially universal though may not be congenital. The distinctive vascular abnormalities of the skin may fade over time, making the diagnosis challenging in older children with this condition.
The brain can be affected in several ways in this syndrome. Some children are born with structural brain anomalies such as cortical dysplasia or polymicrogyria. While developmental delay is nearly universal in this syndrome it is variable in severity, with the majority having mild to moderate delays and a minority having severe cognitive impairment. Some patients are affected with a seizure disorder. White matter abnormalities on magnetic resonance imaging (MRI), suggesting a delay in white matter myelination, is commonly seen in early childhood. Some patients may have asymmetry of the brain, with one side being noticeably larger than the other. One interesting phenomenon that seems very common in this syndrome is the tendency for disproportionate brain growth in the first few years of life, with crossing of percentiles on the head circumerance growth charts. A consequence of this disproportionate brain growth appears to be a significantly increased risk of cerebellar tonsillar herniation (descent of the cerebellar tonsils through the foramen magnum of the skull, resembling a Chiari I malformation neuroradiologically) and ventriculomegaly/hydrocephalus.[6]. Such cerebellar tonsil herniation may occur in up to 70% of children with M-CM.
The medical literature suggests that there is a risk of cardiac arrhythmias in early childhood.[7] The cause for this is unknown. In addition, a variety of different congenital cardiac malformations have been reported in a small number of patients with this disorder.
Like other syndromes associated with disproportionate growth, there appears to be a slightly increased risk of certain types of childhood malignancies in M-CM (such as Wilms' tumor). However, the precise incidence of these malignancies is unclear.
There is no cure for this condition. Treatment is supportive and varies depending on how symptoms present and their severity.
Physical therapy and orthopedic bracing can help young children with gross motor development. Occupational therapy or speech therapy may also assist with developmental delays. Attention from an orthopedic surgeon may be required for leg length discrepancy due to hemihyperplasia.
Children with hemihyperplasia are thought to have an elevated risk for certain types of cancers. Because of the association with hemihyperplasia, screening for these cancers is sometimes prescribed for M-CM patients but there is a lack of general consensus about the best screening methodologies or how often to prescibe them. Screening may consist of regular abdominal ultrasounds to detect Wilms' tumor and AFP testing to detect liver cancer.
Some authors have suggested routine MRI with repeat studies throughout early childhood to assess for the brain anomalies and acquired cerebellar tonsil herniation and ventriculomegaly/hydrocephalus commonly seen in this syndrome. Surgical decompression and ventricular shunting have been options used to treat these problems.
Assessment of cardiac health with echocardiogram and EKG may be prescribed.
Prognosis varies widely depending on severity of symptoms, degree of intellectual impairment, and associated complications. Because the syndrome is rare and so newly identified, there are no long term studies.