Megalencephaly - polymicrogyria - postaxial polydactyly - hydrocephalus

General Information (adopted from Orphanet):

Synonyms, Signs: MEG-PMG-MEGACC SYNDROME
MEGALENCEPHALY, POLYMICROGYRIA, MEGA CORPUS CALLOSUM SYNDROME
MEGALENCEPHALY, MEGA CORPUS CALLOSUM, AND COMPLETE LACK OF MOTOR DEVELOPMENT
MPPH
MPPH syndrome
Number of Symptoms 62
OrphanetNr: 83473
OMIM Id: 603387
ICD-10: Q04.8
UMLs:
MeSH:
MedDRA:
Snomed:

Prevalence, inheritance and age of onset:

Prevalence: 6 cases [Orphanet]
Inheritance: Autosomal dominant
Not applicable
[Orphanet]
Age of onset: Neonatal
Infancy
[Orphanet]

Disease classification (adopted from Orphanet):

Parent Diseases: Genetic syndrome with a central nervous system malformation as major feature
 -Rare genetic disease
Other syndrome with a central nervous system malformation as major feature
 -Rare developmental defect during embryogenesis
 -Rare neurologic disease

Symptom Information: Sort by abundance 

1
 (HPO:0100542) Abnormal localization of kidney Frequent [Orphanet] 64 / 7739
2
 (HPO:0002007) Frontal bossing 366 / 7739
3
 (HPO:0000316) Hypertelorism Frequent [Orphanet] 644 / 7739
4
 (HPO:0000506) Telecanthus Frequent [Orphanet] 156 / 7739
5
 (HPO:0000185) Cleft soft palate 18 / 7739
6
 (HPO:0000637) Long palpebral fissure 21 / 7739
7
 (HPO:0005105) Abnormal nasal morphology Frequent [Orphanet] 114 / 7739
8
 (HPO:0000256) Macrocephaly Very frequent [Orphanet] 298 / 7739
9
 (HPO:0000160) Narrow mouth Frequent [Orphanet] 188 / 7739
10
 (HPO:0001090) Large eyes 20 / 7739
11
 (HPO:0000176) Submucous cleft hard palate 19 / 7739
12
 (HPO:0005280) Depressed nasal bridge Frequent [Orphanet] 381 / 7739
13
 (HPO:0000348) High forehead Frequent [Orphanet] 157 / 7739
14
 (HPO:0011819) Submucous cleft soft palate 12 / 7739
15
 (HPO:0000508) Ptosis 459 / 7739
16
 (HPO:0000618) Blindness 124 / 7739
17
 (HPO:0001263) Global developmental delay 853 / 7739
18
 (HPO:0001250) Seizures Frequent [Orphanet] 1245 / 7739
19
 (HPO:0002267) Exaggerated startle response 42 / 7739
20
 (HPO:0007034) Generalized hyperreflexia 33 / 7739
21
 (HPO:0001347) Hyperreflexia 363 / 7739
22
 (HPO:0002187) Intellectual disability, profound 44 / 7739
23
 (HPO:0001162) Postaxial hand polydactyly Very frequent [Orphanet] 119 / 7739
24
 (HPO:0100259) Postaxial polydactyly 85 / 7739
25
 (HPO:0002943) Thoracic scoliosis 12 / 7739
26
 (HPO:0002808) Kyphosis 289 / 7739
27
 (HPO:0006380) Knee flexion contracture 56 / 7739
28
 (HPO:0001629) Ventricular septal defect Frequent [Orphanet] 316 / 7739
29
 (HPO:0001631) Atria septal defect 274 / 7739
30
 (HPO:0001633) Abnormality of the mitral valve Frequent [Orphanet] 69 / 7739
31
 (HPO:0004760) Congenital septal defect Frequent [Orphanet] 69 / 7739
32
 (HPO:0010775) Vascular ring 3 / 7739
33
 (HPO:0001653) Mitral regurgitation 64 / 7739
34
 (HPO:0008936) Muscular hypotonia of the trunk 77 / 7739
35
 (HPO:0003202) Skeletal muscle atrophy 281 / 7739
36
 (OMIM) Small birth length 1 / 7739
37
 (HPO:0000006) Autosomal dominant inheritance 2518 / 7739
38
 (OMIM) Prominent philtral groove 1 / 7739
39
 (OMIM) Diffuse hypotonia 3 / 7739
40
 (HPO:0007074) Thick corpus callosum 5 / 7739
41
 (OMIM) Mildly thin corpus callosum 1 / 7739
42
 (OMIM) S-scoliosis of thoracic spine 1 / 7739
43
 (OMIM) Cavum septi pellucidi 3 / 7739
44
 (HPO:0000238) Hydrocephalus Very frequent [Orphanet] 278 / 7739
45
 (OMIM) Wide Sylvian fissures with incomplete opercularization 1 / 7739
46
 (OMIM) Increased risk of medulloblastoma (rare) 1 / 7739
47
 (OMIM) Duplicated kidney 4 / 7739
48
 (OMIM) Focal pachygyria 2 / 7739
49
 (HPO:0002079) Hypoplasia of the corpus callosum 161 / 7739
50
 (OMIM) Ventricles slightly enlarged 1 / 7739
51
 (OMIM) Pale optic nerves 2 / 7739
52
 (OMIM) Low bridge 1 / 7739
53
 (OMIM) Asperger-like features 1 / 7739
54
 (HPO:0001302) Pachygyria 60 / 7739
55
 (HPO:0002536) Abnormal cortical gyration Very frequent [Orphanet] 72 / 7739
56
 (HPO:0001355) Megalencephaly 39 / 7739
57
 (OMIM) No language 1 / 7739
58
 (OMIM) Enlarged white matter 1 / 7739
59
 (OMIM) Cavum Vergae 4 / 7739
60
 (HPO:0002126) Polymicrogyria 64 / 7739
61
 (OMIM) Small cavum septum 1 / 7739
62
 (OMIM) Tent-shaped mouth 2 / 7739

Associated genes:

ClinVar (via SNiPA)

Gene symbol Variation Clinical significance Reference

Additional Information:

Description: (OMIM) This disorder comprises megalencephaly, hydrocephalus, and polymicrogyria; polydactyly may also be seen. There is considerable phenotypic similarity between this disorder and the megalencephaly-capillary malformation syndrome (MCAP; 602501) (summary by Gripp et al., 2009).
Diagnosis OMIM Mirzaa et al. (2012) reviewed the phenotypic features of 42 patients with a megalencephalic syndrome in an attempt to clarify and simplify the categorization and diagnosis of these disorders. Statistical analysis of particular features yielded 2 main groups: ...
Clinical Description OMIM Gohlich-Ratmann et al. (1998) reported 3 sporadic cases of in utero-onset megalencephaly. The children were born to healthy nonconsanguineous parents after uneventful pregnancies. Head circumferences were just above the 97th centile at birth in 2 patients, 2 cm ...
Molecular genetics OMIM Riviere et al. (2012) performed exome sequencing in the oldest of 3 affected sibs with MPPH and identified a heterozygous mutation in the PIK3R2 gene (G373R; 603157.0001), which encodes the p85B regulatory subunit of class IA PI3K. Sanger ...