Macrocephaly-capillary malformation
Encyclopedia
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.
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
.. 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. 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.
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.
Vascular
Vascular in zoology and medicine means "related to blood vessels", which are part of the circulatory system. An organ or tissue that is vascularized is heavily endowed with blood vessels and thus richly supplied with blood....
, 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
Macrocephaly
Macrocephaly , occurs when the head is abnormally large; this includes the scalp, the cranial bone, and the contents of the cranium.-Causes:...
, congenital macrosomia, extensive cutaneous capillary malformation (naevus flammeus or port-wine stain
Port-wine stain
A port-wine stain or naevus flammeus is a vascular anomaly consisting of superficial and deep dilated capillaries in the skin which produce a reddish to purplish discoloration of the skin. They are so called for their colour, resembling that of port wine...
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
Hemihypertrophy
Hemihypertrophy is a condition in which one side of the body or a part of one side is larger than the other. Children with hemihypertrophy have an increased risk of developing certain types of cancer, including Wilms tumor and liver cancer...
), polydactyly
Polydactyly
Polydactyly or polydactylism , also known as hyperdactyly, is a congenital physical anomaly in humans, dogs, and cats having supernumerary fingers or toes....
or syndactyly
Syndactyly
Syndactyly is a condition wherein two or more digits are fused together. It occurs normally in some mammals, such as the siamang and kangaroo, but is an unusual condition in humans.-Classification:...
of the hands and feet, lax joints, doughy skin, variable developmental delay and other neurologic problems such as seizures and low muscle tone.
History and Nomenclature
This disorder was recognized as a distinct syndrome in 1997 and named macrocephaly-cutis marmorata telangiectasia congenita or M-CMTC. A new name, macrocephaly-capillary malformation, was recommended in 2007. This new name was chosen to more accurately describe the skin markings associated with this disorder.Diagnosis and Characteristics
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. 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 macrocephalyMacrocephaly
Macrocephaly , occurs when the head is abnormally large; this includes the scalp, the cranial bone, and the contents of the cranium.-Causes:...
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
Cortical dysplasia
Cortical dysplasia is a congenital abnormality where the neurons in an area of the brain failed to migrate in the proper formation in utero. Occasionally neurons will develop that are larger than normal in certain areas. This causes the signals sent through the neurons in these areas to misfire,...
or polymicrogyria
Polymicrogyria
Polymicrogyria is a developmental malformation of the human brain characterized by an excessive number of small convolutions on the surface of the brain...
. 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
White matter
White matter is one of the two components of the central nervous system and consists mostly of myelinated axons. White matter tissue of the freshly cut brain appears pinkish white to the naked eye because myelin is composed largely of lipid tissue veined with capillaries. Its white color is due to...
abnormalities on magnetic resonance imaging
Magnetic resonance imaging
Magnetic resonance imaging , nuclear magnetic resonance imaging , or magnetic resonance tomography is a medical imaging technique used in radiology to visualize detailed internal structures...
(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
Ventriculomegaly
Ventriculomegaly is a brain condition that occurs when the lateral ventricles become dilated. The most common definition uses a width of the atrium of the lateral ventricle of greater than 10 mm. This occurs in around 1% of pregnancies. When this measurement is between 10 and 15 mm, the...
/hydrocephalus
Hydrocephalus
Hydrocephalus , also known as "water in the brain," is a medical condition in which there is an abnormal accumulation of cerebrospinal fluid in the ventricles, or cavities, of the brain. This may cause increased intracranial pressure inside the skull and progressive enlargement of the head,...
.. 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. 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
Wilms' tumor
Wilms' tumor or nephroblastoma is cancer of the kidneys that typically occurs in children, rarely in adults.Its common name is an eponym, referring to Dr. Max Wilms, the German surgeon who first described this kind of tumor....
). However, the precise incidence of these malignancies is unclear.
Treatment
There is no cure for this condition. Treatment is supportive and varies depending on how symptoms present and their severity.Physical therapy
Physical therapy
Physical therapy , often abbreviated PT, is a health care profession. Physical therapy is concerned with identifying and maximizing quality of life and movement potential within the spheres of promotion, prevention, diagnosis, treatment/intervention,and rehabilitation...
and orthopedic bracing can help young children with gross motor development. Occupational therapy
Occupational therapy
Occupational therapy is a discipline that aims to promote health by enabling people to perform meaningful and purposeful activities. Occupational therapists work with individuals who suffer from a mentally, physically, developmentally, and/or emotionally disabling condition by utilizing treatments...
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
Wilms' tumor
Wilms' tumor or nephroblastoma is cancer of the kidneys that typically occurs in children, rarely in adults.Its common name is an eponym, referring to Dr. Max Wilms, the German surgeon who first described this kind of 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
Ventriculomegaly
Ventriculomegaly is a brain condition that occurs when the lateral ventricles become dilated. The most common definition uses a width of the atrium of the lateral ventricle of greater than 10 mm. This occurs in around 1% of pregnancies. When this measurement is between 10 and 15 mm, the...
/hydrocephalus
Hydrocephalus
Hydrocephalus , also known as "water in the brain," is a medical condition in which there is an abnormal accumulation of cerebrospinal fluid in the ventricles, or cavities, of the brain. This may cause increased intracranial pressure inside the skull and progressive enlargement of the head,...
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.