NIH Rare Diseases
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53
The following summary is from Orphanet, a European reference portal for information on rare diseases and orphan drugs.Orpha Number: 60040Disease definitionMegalencephaly-capillary malformation-polymicrogyria syndrome (MCAP) is a polymalfomative syndrome characterized by cutaneous capillary malformations, megalencephaly, cortical brain malformations (most distinctively polymicrogyria), abnormalities of somatic growth with body and brain asymmetry, developmental delay, and characteristic facial dysmorphism.EpidemiologyApproximately 170 patients have been reported in the literature without significant sex predominance.Clinical descriptionSymptoms are usually recognizable at birth. Their severity varies widely among patients. Macrocephaly is a major clinical feature and results from megalencephaly, which sometimes progresses to hydrocephaly. Vascular lesions (not cutis marmorata as previously thought) are often scattered over the limbs, palms, soles and trunk, are frequently pink/red, and are aggravated by crying and emotions. Facial dysmorphism is observed with full cheeks, frontal bossing, and nevus flammeus of the nose and/or philtrum and upper lip. There is a delay in speech and motor skills. Patients may present neurological symptoms, mainly neonatal hypotonia, and less frequently seizures. Additional clinical manifestations include prenatal overgrowth, limb asymmetry, joint laxity, soft skin and thick subcutaneous tissue, and/or toe syndactyly. Some patients develop neoplasias (risk of tumor development estimated at 5-6%). There is also an increased risk for congenital heart defects such as tetralogy of Fallot (see this term).EtiologyRecently, somatic mutations of the PIK3CA gene (3q26), with evidence of postzygotic mosaicism, were found in several patients. PIK3CA encodes the p110α catalytic subunit of phosphatidylinositide 3-kinase, an enzyme that regulates a wide range of processes such as cell growth, metabolism, angiogenesis, and brain development.Diagnostic methodsThree sets of clinical diagnostic criteria have been proposed (Robertson's, Franceschini's, and Martinez-Glez's criteria) that include a combination of major (e.g. macrocephaly) and minor (e.g. neonatal hypotonia, syndactyly, asymmetric overgrowth, capillary malformation, midline facial nevus flammeus and connective tissue defects) criteria. The clinical diagnosis of MCAP may be supported by MRI showing structural cerebral abnormalities like polymicrogyria and focal cortical dysplasia, ventriculomegaly, cerebral/cerebellar asymmetry, cerebellar tonsil herniation, white matter and/or periventricular regions signal abnormalities with increased T2 signal intensity, thick corpus callosum, large venous sinuses and prominent perivascular spaces.Differential diagnosisDifferential diagnoses include Megalencephaly - polymicrogyria - post-axial polydactyly - hydrocephalus, Klippel-Trénaunay syndrome, Beckwith-Wiedemann syndrome, and PTEN hamartoma tumor syndrome (PHTS) (see these terms).Antenatal diagnosisPrenatal ultrasound shows marked fetal overgrowth and progressive macrocephaly in the absence of maternal hyperglycemia or fetal hyperinsulinemia, hydrocephalus, frontal bossing, polydactyly, limb asymmetry, polyhydramnios, hydrops fetalis and pleural effusion.Genetic counselingAll reported cases occurred sporadically; the recurrence risk for sibs is probably low.Management and treatmentManagement requires a multidisciplinary approach (involving neurology, ophthalmology, cardiology, orthopedics, audiometrics, physiotherapy, psychology and dermatology). Neurosurgery can be performed depending on the severity of brain abnormalities (eg. endoscopic third ventriculostomy, posterior fossa decompression). A regular surveillance (brain MRI through the first 6 years of life, renal ultrasound for Wilm's tumor screening through the first 8 years of life) is recommended.PrognosisPrognosis depends on the severity of symptoms. Early death, due to feeding difficulties, complex cardiac heart disease and arrhythmia, has been reported in rare occasions.Visit the Orphanet disease page for more resources.
MalaCards based summary
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Megalencephaly-Capillary Malformation-Polymicrogyria Syndrome, also known as
megalencephaly cutis marmorata telangiectatica congenita, is related to
megalencephaly-polymicrogyria-polydactyly-hydrocephalus syndrome 1 and
megalencephaly, and has symptoms including
seizures An important gene associated with Megalencephaly-Capillary Malformation-Polymicrogyria Syndrome is
PIK3CA (Phosphatidylinositol-4,5-Bisphosphate 3-Kinase Catalytic Subunit Alpha), and among its related pathways/superpathways are
Class I MHC mediated antigen processing and presentation and
Response to elevated platelet cytosolic Ca2+. Affiliated tissues include
skin,
brain and
heart, and related phenotypes are
macrocephaly and
frontal bossing
Genetics Home Reference
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25
Megalencephaly-capillary malformation syndrome (MCAP) is a disorder characterized by overgrowth of several tissues in the body. Its primary features are a large brain (megalencephaly) and abnormalities of small blood vessels in the skin called capillaries (capillary malformations).
OMIM
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57
Megalencephaly-capillary malformation-polymicrogyria syndrome (MCAP) is characterized by a spectrum of anomalies including primary megalencephaly, prenatal overgrowth, brain and body asymmetry, cutaneous vascular malformations, digital anomalies consisting of syndactyly with or without postaxial polydactyly, connective tissue dysplasia involving the skin, subcutaneous tissue, and joints, and cortical brain malformations, most distinctively polymicrogyria (summary by Mirzaa et al., 2012). This disorder is also known as the macrocephaly-capillary malformation (MCM) syndrome (Conway et al., 2007). Mirzaa et al. (2012) suggested use of the term MCAP rather than MCM to reflect the very large brain size, rather than simply large head size, that characterizes this syndrome, and the importance and high frequency of perisylvian polymicrogyria.
(602501)
UniProtKB/Swiss-Prot
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75
Megalencephaly-capillary malformation-polymicrogyria syndrome: A syndrome characterized by a spectrum of anomalies including primary megalencephaly, prenatal overgrowth, brain and body asymmetry, cutaneous vascular malformations, digital anomalies consisting of syndactyly with or without postaxial polydactyly, connective tissue dysplasia involving the skin, subcutaneous tissue, and joints, and cortical brain malformations, most distinctively polymicrogyria.
Rare circulatory system diseases
