MCAP
MCID: MGL038
MIFTS: 51

Megalencephaly-Capillary Malformation-Polymicrogyria Syndrome (MCAP)

Categories: Cardiovascular diseases, Fetal diseases, Genetic diseases, Rare diseases, Skin diseases

Aliases & Classifications for Megalencephaly-Capillary Malformation-Polymicrogyria Syndrome

MalaCards integrated aliases for Megalencephaly-Capillary Malformation-Polymicrogyria Syndrome:

Name: Megalencephaly-Capillary Malformation-Polymicrogyria Syndrome 57 43 58 72 29 6
Megalencephaly-Capillary Malformation Syndrome 57 20 43 58 72 36
Mcmtc 57 43 58 72
Mcap 57 43 58 72
Megalencephaly-Capillary Malformation-Polymicrogyria Syndrome, Somatic 57 13 39
Megalencephaly Cutis Marmorata Telangiectatica Congenita 20 43 70
Macrocephaly-Capillary Malformation 57 20 72
Mcm 57 58 72
Megalencephaly-Cutis Marmorata Telangiectatica Congenita 57 72
Macrocephaly-Cutis Marmorata Telangiectatica Congenita 57 72
Macrocephaly Cutis Marmorata Telangiectatica Congenita 20 43
Macrocephaly-Capillary Malformation Syndrome 43 58
M-Cm 20 43
Megalencephaly-Cutis Marmorata Telangiectatica Congenita Syndrome 58
Macrocephaly-Cutis Marmorata Telangiectatica Congenita Syndrome 58
Macrocephaly-Cutis Marmorata Telangiectatica Congenita; Mcmtc 57
Megalocephaly Cutis Marmorata Telangiectatica Congenita 20
Macrocephaly-Capillary Malformation; Mcm 57
M-Cmtc 20

Characteristics:

Orphanet epidemiological data:

58
megalencephaly-capillary malformation-polymicrogyria syndrome
Inheritance: Not applicable; Prevalence: <1/1000000 (Worldwide); Age of onset: Infancy,Neonatal; Age of death: any age;

OMIM®:

57 (Updated 05-Apr-2021)
Inheritance:
somatic mutation


HPO:

31
megalencephaly-capillary malformation-polymicrogyria syndrome:
Inheritance somatic mutation sporadic


Classifications:

Orphanet: 58  
Rare circulatory system diseases
Rare skin diseases
Developmental anomalies during embryogenesis


Summaries for Megalencephaly-Capillary Malformation-Polymicrogyria Syndrome

GARD : 20 The following summary is from Orphanet, a European reference portal for information on rare diseases and orphan drugs. Orpha Number: 60040 Definition A rare developmental defect during embryogenesis that is characterized by growth dysregulation with overgrowth of the brain and multiple somatic tissues, with capillary skin malformations, megalencephaly (MEG) or hemimegalencephaly (HMEG), cortical brain abnormalities (in particular polymicrogyria), typical facial dysmorphisms, abnormalities of somatic growth with asymmetry of the body and brain, developmental delay and digital anomalies. Epidemiology Over 200 patients have been reported without sex predominance. Clinical description Symptoms are usually recognizable at birth. Their severity varies widely among patients. Megalencephaly is a major clinical feature (MEG: occipitofrontal circumference [OFC] greater than or equal to 3 SD above the mean), which sometimes progresses to hydrocephaly, malformations of cortical development with polymicrogyria and Chiari malformation. Cutaneous capillary anomalies 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 frontal bossing, full cheeks, prominent lips 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, ''doughy'' subcutaneous tissue, postaxial polydactyly and/or syndactyly of toes 2-3 or fingers 3-4. Some patients develop neoplasias (risk of tumor development estimated at 2-3%). There is a slight increased risk for congenital heart defects and/or cardiac rhythm abnormalities. Adult OFCs range from +2 to +10 SDs above the mean. Etiology Somatic mutations of the PIK3CA gene (3q26), with evidence of postzygotic mosaicism, were found in several patients. Two individuals had a de novo germline pathogenic variant in PIK3CA. The gene PIK3CA encodes the alpha catalytic subunit of phosphatidylinositol-4,5-bisphosphate 3-kinase. PIK3CA mutations are found in several benign overgrowth syndromes, collectively known as PIK3CA -related overgrowth spectrum (PROS). The mutational spectrum in children with the disorder is broader than other PIK3CA -related overgrowth disorders. Diagnostic methods The disorder can be diagnosed based on clinical findings in individuals with classic features of MEG or HMEG (major finding 1) associated with neurologic findings of hypotonia, seizures, and mild to severe intellectual disability and characteristic capillary malformations (major finding 2) with focal or generalized somatic overgrowth.. Mosaic mutations of the PIK3CA gene were mainly identified with the advent of massively parallel or next-generation sequencing (NGS) methods. that facilitate detection of low-frequency variation. The level of mosaicism is often lowest in blood-derived DNA, and higher in saliva and fibroblast -derived DNA: multiple tissue samples should be tested, prioritizing samples other than blood. Differential diagnosis Differential diagnoses include Hemimegalencephaly (HMEG), Megalencephaly - polymicrogyria - post-axial polydactyly - hydrocephalus (MPPH), Klippel-Trenaunay syndrome (KTS), Beckwith-Wiedemann syndrome (BWS), PTEN-related overgrowth disorders. Antenatal diagnosis Findings of prenatal ultrasound include marked fetal overgrowth and progressive macrocephaly in the absence of maternal hyperglycemia or fetal hyperinsulinemia, ventriculomegaly, hydrocephalus, frontal bossing, polydactyly, limb asymmetry, polyhydramnios, hydrops fetalis and pleural effusions. Genetic counseling The risk to sibs of a proband with somatic mosaicism for a pathogenic variant in PIK3CA would be expected to be the same as in the general population. However, low-level germline mosaicism may theoretically be present in a parent of a very rare child with a germline PIK3CA pathogenic variant. Management and treatment Management requires a multidisciplinary approach (involving pediatrician, neurologist, ophthalmologist, cardiologist, orthopedist, physiatrist, ENT, and dermatologist ). Neurologic complications (obstructive hydrocephalus, increased intracranial pressure, cerebellar tonsillar ectopia or Chiari malformation; epilepsy in those with HMEG) may warrant neurosurgical intervention. Regular surveillance is recommended (brain MRI in the first 8 years of life, kidney ultrasound for Wilms tumor screening in the first 8 years of life). However, tumor risk in the disorder appears to be lower than in BWS. Prognosis Prognosis depends on the severity of symptoms. Early death, due to complex cardiac heart disease and arrhythmia, has been reported in rare occasions.

MalaCards based summary : Megalencephaly-Capillary Malformation-Polymicrogyria Syndrome, also known as megalencephaly-capillary malformation syndrome, is related to megalencephaly-polymicrogyria-polydactyly-hydrocephalus syndrome 1 and polymicrogyria, 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 mTOR signaling pathway and Pathways of neurodegeneration - multiple diseases. Affiliated tissues include brain, skin and heart, and related phenotypes are macrocephaly and arteriovenous malformation

MedlinePlus Genetics : 43 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).In individuals with MCAP, megalencephaly leads to an unusually large head size (macrocephaly), which is typically evident at birth. After birth, the brain and head continue to grow at a fast rate for the first few years of life; then, the growth slows to a normal rate, although the head remains larger than average. Additional brain abnormalities are common in people with MCAP; these can include excess fluid within the brain (hydrocephalus) and abnormalities in the brain's structure, such as those known as Chiari malformation and polymicrogyria. Abnormal brain development leads to intellectual disability in most affected individuals and can also cause seizures or weak muscle tone (hypotonia). In particular, polymicrogyria is associated with speech delays and difficulty chewing and swallowing.The capillary malformations characteristic of MCAP are composed of enlarged capillaries that increase blood flow near the surface of the skin. These malformations usually look like pink or red spots on the skin. In most affected individuals, capillary malformations occur on the face, particularly the nose, the upper lip, and the area between the nose and upper lip (the philtrum). In other people with MCAP, the malformations appear as patches spread over the body or as a reddish net-like pattern on the skin (cutis marmorata).In some people with MCAP, excessive growth affects not only the brain but other individual parts of the body, which is known as segmental overgrowth. This can lead to one arm or leg that is bigger or longer than the other or a few oversized fingers or toes. Some affected individuals have fusion of the skin between two or more fingers or toes (cutaneous syndactyly).Additional features of MCAP can include flexible joints and skin that stretches easily. Some affected individuals are said to have doughy skin because the tissue under the skin is unusually thick and soft.The gene involved in MCAP is also associated with several types of cancer. Only a small number of individuals with MCAP have developed tumors (in particular, a childhood form of kidney cancer known as Wilms tumor and noncancerous tumors in the nervous system known as meningiomas).

OMIM® : 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) (Updated 05-Apr-2021)

KEGG : 36 Megalencephaly-capillary malformation (MCAP) syndrome is a rare overgrowth syndrome. The main symptoms are progressive megalencephaly, polymicrogyria, capillary malformations, syndactyly, and connective tissue dysplasia. Mutations in PIK3CA have been reported in MCAP patients.

UniProtKB/Swiss-Prot : 72 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.

Wikipedia : 73 Macrocephaly-capillary malformation (M-CM) is a multiple malformation syndrome causing abnormal body and... more...

Related Diseases for Megalencephaly-Capillary Malformation-Polymicrogyria Syndrome

Diseases related to Megalencephaly-Capillary Malformation-Polymicrogyria Syndrome via text searches within MalaCards or GeneCards Suite gene sharing:

(show top 50) (show all 71)
# Related Disease Score Top Affiliating Genes
1 megalencephaly-polymicrogyria-polydactyly-hydrocephalus syndrome 1 31.5 PIK3R2 AKT3
2 polymicrogyria 30.4 PIK3R2 AKT3
3 megalencephaly 29.9 PIK3R2 PIK3CA AKT3
4 hemimegalencephaly 29.8 PIK3CA AKT3
5 megalencephaly-polymicrogyria-polydactyly-hydrocephalus syndrome 2 11.0
6 klippel-trenaunay-weber syndrome 10.9
7 atrial septal aneurysm 10.5
8 macrocephaly/megalencephaly syndrome, autosomal recessive 10.5
9 polymicrogyria with or without vascular-type ehlers-danlos syndrome 10.5
10 candidiasis, familial, 1 10.4
11 cardiac arrhythmia 10.4
12 dowling-degos disease 1 10.4
13 retinoblastoma 10.4
14 telangiectasis 10.4
15 heart septal defect 10.4
16 atrial heart septal defect 10.4
17 hyperinsulinism 10.4
18 intracranial hypertension 10.4
19 hypermobile ehlers-danlos syndrome 10.4
20 lymphangiectasis 10.4
21 weber syndrome 10.4
22 aneurysm 10.4
23 angioosteohypertrophic syndrome 10.4
24 multiple congenital anomalies/dysmorphic syndrome-intellectual disability 10.4
25 chromosome 2q35 duplication syndrome 10.2
26 cutis marmorata telangiectatica congenita 10.2
27 pik3ca-related overgrowth spectrum 10.2
28 pik3ca-related overgrowth syndrome 10.2
29 overgrowth syndrome 10.2
30 tetralogy of fallot 10.2
31 hemihyperplasia, isolated 10.2
32 hemangioma 10.2
33 hypotonia 10.2
34 syringomyelia, noncommunicating isolated 10.1
35 scoliosis 10.1
36 syringomyelia 10.1
37 hypoglycemia 10.1
38 growth hormone deficiency 10.1
39 polydactyly 10.1
40 chiari malformation type ii 10.0
41 meningioma, familial 10.0
42 capillary malformation of the lower lip, lymphatic malformation of face and neck, asymmetry of face and limbs, and partial/generalized overgrowth 10.0
43 thrombosis 10.0
44 intracranial meningioma 10.0
45 epilepsy 10.0
46 capillary hemangioma 10.0
47 sagittal sinus thrombosis 10.0
48 secretory meningioma 10.0
49 lymphoplasmacyte-rich meningioma 10.0
50 polyhydramnios 10.0

Graphical network of the top 20 diseases related to Megalencephaly-Capillary Malformation-Polymicrogyria Syndrome:



Diseases related to Megalencephaly-Capillary Malformation-Polymicrogyria Syndrome

Symptoms & Phenotypes for Megalencephaly-Capillary Malformation-Polymicrogyria Syndrome

Human phenotypes related to Megalencephaly-Capillary Malformation-Polymicrogyria Syndrome:

58 31 (show top 50) (show all 57)
# Description HPO Frequency Orphanet Frequency HPO Source Accession
1 macrocephaly 58 31 hallmark (90%) Very frequent (99-80%) HP:0000256
2 arteriovenous malformation 58 31 hallmark (90%) Very frequent (99-80%) HP:0100026
3 telangiectasia of the skin 58 31 hallmark (90%) Very frequent (99-80%) HP:0100585
4 wide mouth 58 31 hallmark (90%) Very frequent (99-80%) HP:0000154
5 facial asymmetry 58 31 hallmark (90%) Very frequent (99-80%) HP:0000324
6 hand polydactyly 58 31 hallmark (90%) Very frequent (99-80%) HP:0001161
7 foot polydactyly 58 31 hallmark (90%) Very frequent (99-80%) HP:0001829
8 nevus flammeus 58 31 hallmark (90%) Very frequent (99-80%) HP:0001052
9 finger syndactyly 58 31 hallmark (90%) Very frequent (99-80%) HP:0006101
10 visceral angiomatosis 58 31 hallmark (90%) Very frequent (99-80%) HP:0100761
11 toe syndactyly 58 31 hallmark (90%) Very frequent (99-80%) HP:0001770
12 asymmetric growth 58 31 hallmark (90%) Very frequent (99-80%) HP:0100555
13 intellectual disability 58 31 frequent (33%) Frequent (79-30%) HP:0001249
14 failure to thrive 58 31 frequent (33%) Frequent (79-30%) HP:0001508
15 frontal bossing 58 31 frequent (33%) Frequent (79-30%) HP:0002007
16 hydrocephalus 58 31 frequent (33%) Frequent (79-30%) HP:0000238
17 global developmental delay 58 31 frequent (33%) Frequent (79-30%) HP:0001263
18 full cheeks 58 31 frequent (33%) Frequent (79-30%) HP:0000293
19 aplasia/hypoplasia of the cerebellum 58 31 frequent (33%) Frequent (79-30%) HP:0007360
20 ventriculomegaly 58 31 frequent (33%) Frequent (79-30%) HP:0002119
21 joint hyperflexibility 58 31 frequent (33%) Frequent (79-30%) HP:0005692
22 high forehead 58 31 frequent (33%) Frequent (79-30%) HP:0000348
23 hypermelanotic macule 58 31 frequent (33%) Frequent (79-30%) HP:0001034
24 cutis marmorata 58 31 frequent (33%) Frequent (79-30%) HP:0000965
25 hypotonia 31 frequent (33%) HP:0001252
26 depressed nasal bridge 58 31 occasional (7.5%) Occasional (29-5%) HP:0005280
27 optic atrophy 58 31 occasional (7.5%) Occasional (29-5%) HP:0000648
28 arrhythmia 58 31 occasional (7.5%) Occasional (29-5%) HP:0011675
29 deeply set eye 58 31 occasional (7.5%) Occasional (29-5%) HP:0000490
30 arnold-chiari malformation 58 31 occasional (7.5%) Occasional (29-5%) HP:0002308
31 cerebral ischemia 58 31 occasional (7.5%) Occasional (29-5%) HP:0002637
32 polymicrogyria 58 31 occasional (7.5%) Occasional (29-5%) HP:0002126
33 megalencephaly 31 HP:0001355
34 muscular hypotonia 58 Frequent (79-30%)
35 hypertelorism 31 HP:0000316
36 smooth philtrum 31 HP:0000319
37 malformation of the heart and great vessels 58 Occasional (29-5%)
38 hernia 31 HP:0100790
39 epicanthus 31 HP:0000286
40 joint laxity 31 HP:0001388
41 downslanted palpebral fissures 31 HP:0000494
42 neoplasm 58 Occasional (29-5%)
43 microphthalmia 31 HP:0000568
44 leukemia 31 HP:0001909
45 ventricular septal defect 31 HP:0001629
46 broad forehead 31 HP:0000337
47 abnormality of nervous system morphology 58 Frequent (79-30%)
48 meningioma 31 HP:0002858
49 large earlobe 31 HP:0009748
50 nephroblastoma 31 HP:0002667

Symptoms via clinical synopsis from OMIM®:

57 (Updated 05-Apr-2021)
Neurologic Central Nervous System:
seizures
hydrocephalus
ventriculomegaly
polymicrogyria
cavum septum pellucidum
more
Head And Neck Eyes:
hypertelorism
epicanthus
downslanting palpebral fissures
unilateral microphthalmia

Skeletal:
joint laxity

Skin Nails Hair Skin:
cutis marmorata
thick, loose, doughy skin
cutaneous vascular malformations
patchy, reticular stains

Skeletal Feet:
polydactyly
syndactyly

Neoplasia:
increased risk of leukemia
increased risk of meningioma
increased risk of wilms tumor

Head And Neck Nose:
flattened nasal bridge

Growth Other:
somatic overgrowth, asymmetric
hemihyperplasia

Muscle Soft Tissue:
thickened subcutaneous tissue

Head And Neck Head:
megalencephaly
macrocephaly, progressive in infancy

Head And Neck Face:
smooth philtrum
broad forehead

Cardiovascular Heart:
ventricular septal defect

Skeletal Hands:
polydactyly
syndactyly

Growth Weight:
increased birth weight

Growth Height:
increased birth length

Head And Neck Ears:
fleshy earlobes

Head And Neck Mouth:
narrow arched palate

Clinical features from OMIM®:

602501 (Updated 05-Apr-2021)

UMLS symptoms related to Megalencephaly-Capillary Malformation-Polymicrogyria Syndrome:


seizures

GenomeRNAi Phenotypes related to Megalencephaly-Capillary Malformation-Polymicrogyria Syndrome according to GeneCards Suite gene sharing:

26 (show all 12)
# Description GenomeRNAi Source Accession Score Top Affiliating Genes
1 Decreased viability GR00055-A-1 10.11 PIK3CA
2 Decreased viability GR00055-A-2 10.11 PIK3CA
3 Decreased viability GR00173-A 10.11 PIK3R2
4 Decreased viability GR00221-A-1 10.11 AKT3 PIK3R2 PIK3CA
5 Decreased viability GR00221-A-2 10.11 AKT3 PIK3R2 PIK3CA
6 Decreased viability GR00221-A-3 10.11 AKT3
7 Decreased viability GR00221-A-4 10.11 AKT3 PIK3R2 PIK3CA
8 Decreased viability GR00249-S 10.11 PIK3R2
9 Decreased viability GR00301-A 10.11 AKT3 PIK3R2
10 Decreased viability GR00402-S-2 10.11 PIK3CA
11 Decreased cell migration GR00055-A-1 9.13 AKT3 PIK3R2
12 Decreased cell migration GR00055-A-3 9.13 PIK3CA

MGI Mouse Phenotypes related to Megalencephaly-Capillary Malformation-Polymicrogyria Syndrome:

46
# Description MGI Source Accession Score Top Affiliating Genes
1 neoplasm MP:0002006 8.8 AKT3 PIK3CA PIK3R2

Drugs & Therapeutics for Megalencephaly-Capillary Malformation-Polymicrogyria Syndrome

Search Clinical Trials , NIH Clinical Center for Megalencephaly-Capillary Malformation-Polymicrogyria Syndrome

Genetic Tests for Megalencephaly-Capillary Malformation-Polymicrogyria Syndrome

Genetic tests related to Megalencephaly-Capillary Malformation-Polymicrogyria Syndrome:

# Genetic test Affiliating Genes
1 Megalencephaly-Capillary Malformation-Polymicrogyria Syndrome 29 PIK3CA

Anatomical Context for Megalencephaly-Capillary Malformation-Polymicrogyria Syndrome

MalaCards organs/tissues related to Megalencephaly-Capillary Malformation-Polymicrogyria Syndrome:

40
Brain, Skin, Heart, Cerebellum, Eye, Tonsil, Breast

Publications for Megalencephaly-Capillary Malformation-Polymicrogyria Syndrome

Articles related to Megalencephaly-Capillary Malformation-Polymicrogyria Syndrome:

(show all 42)
# Title Authors PMID Year
1
Megalencephaly-capillary malformation (MCAP) and megalencephaly-polydactyly-polymicrogyria-hydrocephalus (MPPH) syndromes: two closely related disorders of brain overgrowth and abnormal brain and body morphogenesis. 6 57 61
22228622 2012
2
De novo somatic mutations in components of the PI3K-AKT3-mTOR pathway cause hemimegalencephaly. 57 6
22729223 2012
3
De novo germline and postzygotic mutations in AKT3, PIK3R2 and PIK3CA cause a spectrum of related megalencephaly syndromes. 57 6
22729224 2012
4
A combination of genetic and biochemical analyses for the diagnosis of PI3K-AKT-mTOR pathway-associated megalencephaly. 6
28086757 2017
5
Characterisation of mutations of the phosphoinositide-3-kinase regulatory subunit, PIK3R2, in perisylvian polymicrogyria: a next-generation sequencing study. 6
26520804 2015
6
Sudden death in a case of megalencephaly capillary malformation associated with a de novo mutation in AKT3. 6
25416470 2015
7
Germline activating AKT3 mutation associated with megalencephaly, polymicrogyria, epilepsy and hypoglycemia. 6
25523067 2015
8
AKT3 and PIK3R2 mutations in two patients with megalencephaly-related syndromes: MCAP and MPPH. 6
23745724 2014
9
Megalencephaly syndromes: exome pipeline strategies for detecting low-level mosaic mutations. 6
24497998 2014
10
Macrocephaly-capillary malformation: Analysis of 13 patients and review of the diagnostic criteria. 57
21077203 2010
11
Significant overlap and possible identity of macrocephaly capillary malformation and megalencephaly polymicrogyria-polydactyly hydrocephalus syndromes. 57
19353582 2009
12
Macrocephaly-cutis marmorata telangiectatica congenita: a report on the natural history of a mild case. 57
18978660 2008
13
Accurately renaming macrocephaly-cutis marmorata telangiectatica congenita (M-CMTC) as macrocephaly-capillary malformation (M-CM). 57
17963258 2007
14
Neuroimaging findings in macrocephaly-capillary malformation: a longitudinal study of 17 patients. 57
18000912 2007
15
Oncogenic PIK3CA mutations occur in epidermal nevi and seborrheic keratoses with a characteristic mutation pattern. 6
17673550 2007
16
PIK3CA gene is frequently mutated in breast carcinomas and hepatocellular carcinomas. 6
15608678 2005
17
MRI and neurological findings in macrocephaly-cutis marmorata telangiectatica congenita syndrome: report of ten cases and review of the literature. 57
16080291 2005
18
Mutation of the PIK3CA gene in ovarian and breast cancer. 6
15520168 2004
19
Macrocephaly-cutis marmorata telangiectatica congenita: report of six new patients and a review. 57
15368495 2004
20
Macrocephaly-cutis marmorata telangiectatica congenita: seven cases including two with unusual cerebral manifestations. 57
15039980 2004
21
Macrocephaly-cutis marmorata telangiectatica congenita: report of a patient with a translocation. 57
12872811 2003
22
Association of arrhythmia and sudden death in macrocephaly-cutis marmorata telangiectatica congenita syndrome. 57
11477607 2001
23
Macrocephaly-Cutis marmorata telangiectatica congenita without cutis marmorata? 57
10710221 2000
24
MRI findings in macrocephaly-cutis marmorata telangiectatica congenita. 57
9511980 1998
25
The macrocephaly-cutis marmorata telangiectatica congenita syndrome. Long-term follow-up data in 4 children and adolescents. 57
9894160 1998
26
Macrocephaly with cutis marmorata, haemangioma and syndactyly--a distinctive overgrowth syndrome. 57
9354837 1997
27
Macrocephaly-cutis marmorata telangiectatica congenita: a distinct disorder with developmental delay and connective tissue abnormalities. 57
9129744 1997
28
Detailed analysis of phenotypes and genotypes in megalencephaly-capillary malformation-polymicrogyria syndrome caused by somatic mosaicism of PIK3CA mutations. 61
32778138 2020
29
Growth hormone deficiency in megalencephaly-capillary malformation syndrome: An association with activating mutations in PIK3CA. 61
31729162 2020
30
One of the First Cases with PIK3CA-related Overgrowth Spectrum (PROS) in Saudi Arabia: A Case Report and Literature Review. 61
31929958 2020
31
Gingival Biopsy to Detect Mosaicism in Overgrowth Syndromes: Report of Two Cases of Megalencephaly-Capillary Malformation Syndrome with Periodontal Anomalies. 61
33005459 2020
32
Clinical pitfalls in the diagnosis of segmental overgrowth syndromes: a child with the c.2740G > A mutation in PIK3CA gene. 61
30231930 2018
33
In vitro efficacy of ARQ 092, an allosteric AKT inhibitor, on primary fibroblast cells derived from patients with PIK3CA-related overgrowth spectrum (PROS). 61
29549527 2018
34
Commentary on "Megalencephaly-capillary malformation-polymicrogyria syndrome: the first case report in Korea". 61
29441111 2018
35
Update on classification and diagnosis of vascular malformations. 61
28654575 2017
36
Megalencephaly-capillary malformation-polymicrogyria syndrome: the first case report in Korea. 61
28018470 2016
37
Severe holocord syrinx in a child with megalencephaly-capillary malformation syndrome. 61
27035547 2016
38
Detection of a mosaic PIK3CA mutation in dental DNA from a child with megalencephaly capillary malformation syndrome. 61
26351730 2016
39
Capillary malformations: a classification using specific names for specific skin disorders. 61
25864701 2015
40
Germline PTPN11 and somatic PIK3CA variant in a boy with megalencephaly-capillary malformation syndrome (MCAP)--pure coincidence? 61
24939587 2015
41
Expanding the differential diagnosis of fetal hydrops: an unusual prenatal presentation of megalencephaly-capillary malformation syndrome. 61
23754335 2013
42
PIK3CA-Related Segmental Overgrowth 61
23946963 2013

Variations for Megalencephaly-Capillary Malformation-Polymicrogyria Syndrome

ClinVar genetic disease variations for Megalencephaly-Capillary Malformation-Polymicrogyria Syndrome:

6 (show all 15)
# Gene Name Type Significance ClinVarId dbSNP ID Position
1 PIK3CA NM_006218.4(PIK3CA):c.1133G>A (p.Cys378Tyr) SNV Pathogenic 39704 rs397514565 GRCh37: 3:178922364-178922364
GRCh38: 3:179204576-179204576
2 PIK3CA NM_006218.4(PIK3CA):c.335T>A (p.Ile112Asn) SNV Pathogenic 218236 rs863225460 GRCh37: 3:178916948-178916948
GRCh38: 3:179199160-179199160
3 AKT3 NM_005465.7(AKT3):c.686A>G (p.Asn229Ser) SNV Pathogenic 39815 rs397514605 GRCh37: 1:243776983-243776983
GRCh38: 1:243613681-243613681
4 PIK3CA NM_006218.4(PIK3CA):c.3139C>T (p.His1047Tyr) SNV Pathogenic 39705 rs121913281 GRCh37: 3:178952084-178952084
GRCh38: 3:179234296-179234296
5 PIK3CA NM_006218.4(PIK3CA):c.3139C>T (p.His1047Tyr) SNV Pathogenic 39705 rs121913281 GRCh37: 3:178952084-178952084
GRCh38: 3:179234296-179234296
6 PIK3CA NM_006218.4(PIK3CA):c.3140A>T (p.His1047Leu) SNV Pathogenic 13653 rs121913279 GRCh37: 3:178952085-178952085
GRCh38: 3:179234297-179234297
7 PIK3CA NM_006218.4(PIK3CA):c.1356_1358AGA[1] (p.Glu453del) Microsatellite Pathogenic 39706 rs587776933 GRCh37: 3:178928078-178928080
GRCh38: 3:179210290-179210292
8 PIK3CA NM_006218.4(PIK3CA):c.1633G>A (p.Glu545Lys) SNV Pathogenic 13655 rs104886003 GRCh37: 3:178936091-178936091
GRCh38: 3:179218303-179218303
9 PIK3R2 NM_005027.4(PIK3R2):c.1117G>A (p.Gly373Arg) SNV Pathogenic 39808 rs587776934 GRCh37: 19:18273784-18273784
GRCh38: 19:18162974-18162974
10 PIK3CA NM_006218.4(PIK3CA):c.1357G>A (p.Glu453Lys) SNV Pathogenic 376470 rs1057519925 GRCh37: 3:178928079-178928079
GRCh38: 3:179210291-179210291
11 PIK3CA NM_006218.4(PIK3CA):c.2740G>A (p.Gly914Arg) SNV Pathogenic/Likely pathogenic 39703 rs587776932 GRCh37: 3:178947865-178947865
GRCh38: 3:179230077-179230077
12 PIK3CA NM_006218.4(PIK3CA):c.1345C>T (p.Pro449Ser) SNV Likely pathogenic 864863 GRCh37: 3:178928067-178928067
GRCh38: 3:179210279-179210279
13 PIK3CA NM_006218.4(PIK3CA):c.436G>A (p.Val146Ile) SNV Uncertain significance 526641 rs755969956 GRCh37: 3:178917561-178917561
GRCh38: 3:179199773-179199773
14 PIK3CA NM_006218.4(PIK3CA):c.1A>G (p.Met1Val) SNV Uncertain significance 844646 GRCh37: 3:178916614-178916614
GRCh38: 3:179198826-179198826
15 PIK3CA NM_006218.4(PIK3CA):c.1130C>G (p.Pro377Arg) SNV Uncertain significance 403909 rs113613074 GRCh37: 3:178922361-178922361
GRCh38: 3:179204573-179204573

UniProtKB/Swiss-Prot genetic disease variations for Megalencephaly-Capillary Malformation-Polymicrogyria Syndrome:

72 (show all 15)
# Symbol AA change Variation ID SNP ID
1 PIK3CA p.Arg88Gln VAR_026167 rs121913287
2 PIK3CA p.Glu545Lys VAR_026178 rs104886003
3 PIK3CA p.Tyr1021Cys VAR_026184 rs121913288
4 PIK3CA p.Ala1035Val VAR_026189 rs124294537
5 PIK3CA p.Met1043Ile VAR_026190 rs121913283
6 PIK3CA p.His1047Tyr VAR_026193 rs121913281
7 PIK3CA p.Glu81Lys VAR_069251 rs105751992
8 PIK3CA p.Gly364Arg VAR_069252
9 PIK3CA p.Glu365Lys VAR_069253 rs106479373
10 PIK3CA p.Cys378Tyr VAR_069254 rs397514565
11 PIK3CA p.Glu726Lys VAR_069256 rs867262025
12 PIK3CA p.Gly914Arg VAR_069257 rs587776932
13 PIK3CA p.Thr1025Ala VAR_069258 rs397517202
14 PIK3CA p.Gly1049Ser VAR_069259 rs121913277
15 PIK3CA p.Ile112Asn VAR_075634 rs863225460

Expression for Megalencephaly-Capillary Malformation-Polymicrogyria Syndrome

Search GEO for disease gene expression data for Megalencephaly-Capillary Malformation-Polymicrogyria Syndrome.

Pathways for Megalencephaly-Capillary Malformation-Polymicrogyria Syndrome

Pathways related to Megalencephaly-Capillary Malformation-Polymicrogyria Syndrome according to KEGG:

36
# Name Kegg Source Accession
1 mTOR signaling pathway hsa04150

Pathways related to Megalencephaly-Capillary Malformation-Polymicrogyria Syndrome according to GeneCards Suite gene sharing:

(show top 50) (show all 129)
# Super pathways Score Top Affiliating Genes
1
Show member pathways
13.16 PIK3R2 PIK3CA AKT3
2
Show member pathways
13.15 PIK3R2 PIK3CA AKT3
3
Show member pathways
13.1 PIK3R2 PIK3CA AKT3
4
Show member pathways
13.04 PIK3R2 PIK3CA AKT3
5
Show member pathways
12.96 PIK3R2 PIK3CA AKT3
6
Show member pathways
12.89 PIK3R2 PIK3CA AKT3
7
Show member pathways
12.84 PIK3R2 PIK3CA AKT3
8
Show member pathways
12.79 PIK3R2 PIK3CA AKT3
9
Show member pathways
12.75 PIK3R2 PIK3CA AKT3
10
Show member pathways
12.72 PIK3R2 PIK3CA AKT3
11
Show member pathways
12.71 PIK3R2 PIK3CA AKT3
12
Show member pathways
12.7 PIK3R2 PIK3CA AKT3
13
Show member pathways
12.69 PIK3R2 PIK3CA AKT3
14
Show member pathways
12.68 PIK3R2 PIK3CA AKT3
15
Show member pathways
12.68 PIK3R2 PIK3CA AKT3
16 12.66 PIK3R2 PIK3CA AKT3
17
Show member pathways
12.65 PIK3R2 PIK3CA AKT3
18 12.63 PIK3R2 PIK3CA AKT3
19
Show member pathways
12.61 PIK3R2 PIK3CA AKT3
20
Show member pathways
12.6 PIK3R2 PIK3CA AKT3
21
Show member pathways
12.6 PIK3R2 PIK3CA AKT3
22
Show member pathways
12.58 PIK3R2 PIK3CA AKT3
23
Show member pathways
12.57 PIK3R2 PIK3CA AKT3
24
Show member pathways
12.56 PIK3R2 PIK3CA AKT3
25
Show member pathways
12.55 PIK3R2 PIK3CA AKT3
26
Show member pathways
12.52 PIK3R2 PIK3CA AKT3
27
Show member pathways
12.51 PIK3R2 PIK3CA AKT3
28
Show member pathways
12.5 PIK3R2 PIK3CA AKT3
29
Show member pathways
12.49 PIK3R2 PIK3CA AKT3
30
Show member pathways
12.48 PIK3R2 PIK3CA AKT3
31
Show member pathways
12.47 PIK3R2 PIK3CA AKT3
32
Show member pathways
12.45 PIK3R2 PIK3CA AKT3
33
Show member pathways
12.44 PIK3R2 PIK3CA AKT3
34
Show member pathways
12.44 PIK3R2 PIK3CA AKT3
35
Show member pathways
12.42 PIK3R2 PIK3CA AKT3
36
Show member pathways
12.36 PIK3R2 PIK3CA AKT3
37
Show member pathways
12.35 PIK3R2 PIK3CA AKT3
38
Show member pathways
12.34 PIK3R2 PIK3CA AKT3
39
Show member pathways
12.32 PIK3R2 PIK3CA AKT3
40
Show member pathways
12.31 PIK3R2 PIK3CA AKT3
41
Show member pathways
12.28 PIK3R2 PIK3CA AKT3
42
Show member pathways
12.27 PIK3R2 PIK3CA AKT3
43
Show member pathways
12.27 PIK3R2 PIK3CA AKT3
44 12.27 PIK3R2 PIK3CA AKT3
45
Show member pathways
12.27 PIK3R2 PIK3CA AKT3
46
Show member pathways
12.27 PIK3R2 PIK3CA AKT3
47
Show member pathways
12.26 PIK3R2 PIK3CA AKT3
48
Show member pathways
12.26 PIK3R2 PIK3CA AKT3
49
Show member pathways
12.23 PIK3R2 PIK3CA AKT3
50 12.21 PIK3R2 PIK3CA AKT3

GO Terms for Megalencephaly-Capillary Malformation-Polymicrogyria Syndrome

Cellular components related to Megalencephaly-Capillary Malformation-Polymicrogyria Syndrome according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 phosphatidylinositol 3-kinase complex GO:0005942 8.62 PIK3R2 PIK3CA

Biological processes related to Megalencephaly-Capillary Malformation-Polymicrogyria Syndrome according to GeneCards Suite gene sharing:

(show all 11)
# Name GO ID Score Top Affiliating Genes
1 leukocyte migration GO:0050900 9.49 PIK3R2 PIK3CA
2 positive regulation of protein kinase B signaling GO:0051897 9.48 PIK3R2 PIK3CA
3 T cell receptor signaling pathway GO:0050852 9.46 PIK3R2 PIK3CA
4 Fc-epsilon receptor signaling pathway GO:0038095 9.43 PIK3R2 PIK3CA
5 Fc-gamma receptor signaling pathway involved in phagocytosis GO:0038096 9.4 PIK3R2 PIK3CA
6 phosphatidylinositol biosynthetic process GO:0006661 9.37 PIK3R2 PIK3CA
7 vascular endothelial growth factor receptor signaling pathway GO:0048010 9.32 PIK3R2 PIK3CA
8 phosphatidylinositol phosphorylation GO:0046854 9.26 PIK3R2 PIK3CA
9 phosphatidylinositol-mediated signaling GO:0048015 9.16 PIK3R2 PIK3CA
10 phosphatidylinositol 3-kinase signaling GO:0014065 8.96 PIK3R2 PIK3CA
11 positive regulation of TOR signaling GO:0032008 8.62 PIK3CA AKT3

Sources for Megalencephaly-Capillary Malformation-Polymicrogyria Syndrome

3 CDC
7 CNVD
9 Cosmic
10 dbSNP
11 DGIdb
17 EFO
18 ExPASy
19 FMA
20 GARD
28 GO
29 GTR
30 HMDB
31 HPO
32 ICD10
33 ICD10 via Orphanet
34 ICD9CM
35 IUPHAR
36 KEGG
37 LifeMap
39 LOVD
41 MedGen
44 MeSH
45 MESH via Orphanet
46 MGI
49 NCI
50 NCIt
51 NDF-RT
53 NINDS
54 Novoseek
56 OMIM via Orphanet
57 OMIM® (Updated 05-Apr-2021)
61 PubMed
63 QIAGEN
68 SNOMED-CT via HPO
69 Tocris
70 UMLS
71 UMLS via Orphanet
Content
Loading form....