MUSCULAR DYSTROPHY-DYSTROGLYCANOPATHY (CONGENITAL WITH BRAIN AND EYEANOMALIES), TYPE A, 4

General Information (adopted from Orphanet):

Synonyms, Signs: FUKUYAMA CONGENITAL MUSCULAR DYSTROPHY
WALKER-WARBURG SYNDROME OR MUSCLE-EYE-BRAIN DISEASE, FKTN-RELATED
MDDGA4
FCMD
Number of Symptoms 62
OrphanetNr:
OMIM Id: 253800
ICD-10:
UMLs:
MeSH:
MedDRA:
Snomed:

Prevalence, inheritance and age of onset:

Prevalence: No data available.
Inheritance: Autosomal recessive inheritance
[Omim]
Age of onset: Infantile onset
[Omim]

Disease classification (adopted from Orphanet):

Parent Diseases: No data available.

Symptom Information: Sort by abundance 

1
(HPO:0002084) Encephalocele 70 / 7739
2
(HPO:0000568) Microphthalmia 183 / 7739
3
(HPO:0011815) Cephalocele 5 / 7739
4
(HPO:0000545) Myopia 286 / 7739
5
(HPO:0000518) Cataract 454 / 7739
6
(HPO:0000556) Retinal dystrophy 65 / 7739
7
(HPO:0000486) Strabismus 576 / 7739
8
(HPO:0001135) Chorioretinal dystrophy 18 / 7739
9
(HPO:0000648) Optic atrophy 238 / 7739
10
(HPO:0000541) Retinal detachment 87 / 7739
11
(HPO:0007731) Chorioretinal dysplasia 16 / 7739
12
(HPO:0000540) Hypermetropia 99 / 7739
13
(HPO:0000496) Abnormality of eye movement 79 / 7739
14
(HPO:0007973) Retinal dysplasia rare [HPO:skoehler] 27 / 7739
15
(HPO:0002267) Exaggerated startle response rare [HPO:skoehler] 42 / 7739
16
(HPO:0001284) Areflexia 198 / 7739
17
(HPO:0001249) Intellectual disability 1089 / 7739
18
(HPO:0001250) Seizures 1245 / 7739
19
(HPO:0002650) Scoliosis 705 / 7739
20
(HPO:0001371) Flexion contracture 220 / 7739
21
(HPO:0003306) Spinal rigidity 30 / 7739
22
(HPO:0008981) Calf muscle hypertrophy 28 / 7739
23
(HPO:0001685) Myocardial fibrosis 30 / 7739
24
(HPO:0001642) Pulmonic stenosis 89 / 7739
25
(HPO:0001631) Atria septal defect 274 / 7739
26
(HPO:0001669) Transposition of the great arteries 36 / 7739
27
(HPO:0001644) Dilated cardiomyopathy 141 / 7739
28
(HPO:0003236) Elevated serum creatine phosphokinase 214 / 7739
29
(HPO:0002093) Respiratory insufficiency 410 / 7739
30
(HPO:0003202) Skeletal muscle atrophy 281 / 7739
31
(HPO:0003560) Muscular dystrophy 88 / 7739
32
(HPO:0001324) Muscle weakness 859 / 7739
33
(HPO:0003741) Congenital muscular dystrophy 22 / 7739
34
(HPO:0010547) Muscle flaccidity 466 / 7739
35
(HPO:0008947) Infantile muscular hypotonia 482 / 7739
36
(HPO:0001252) Muscular hypotonia 990 / 7739
37
(HPO:0007260) Type II lissencephaly 13 / 7739
38
(HPO:0001360) Holoprosencephaly rare [HPO:skoehler] 29 / 7739
39
(HPO:0001274) Agenesis of corpus callosum 142 / 7739
40
(HPO:0002350) Cerebellar cyst 14 / 7739
41
(HPO:0003593) Infantile onset 249 / 7739
42
(HPO:0002365) Hypoplasia of the brainstem 41 / 7739
43
(OMIM) Focal interhemispheric fusion 1 / 7739
44
(HPO:0002139) Arrhinencephaly 13 / 7739
45
(HPO:0007348) Hypoplasia of the pyramidal tract 1 / 7739
46
(OMIM) Double subaortic ventricular defect 1 / 7739
47
(OMIM) Hypoplastic left ventricular outlet 1 / 7739
48
(OMIM) White matter changes 7 / 7739
49
(OMIM) Poor motor development 3 / 7739
50
(HPO:0002126) Polymicrogyria 64 / 7739
51
(OMIM) Low density white matter on CT scan 1 / 7739
52
(HPO:0001339) Lissencephaly 30 / 7739
53
(HPO:0001321) Cerebellar hypoplasia 114 / 7739
54
(HPO:0001302) Pachygyria 60 / 7739
55
(OMIM) Cardiac defects 5 / 7739
56
(OMIM) Pyramidal tract hypoplasia 1 / 7739
57
(OMIM) Leptomeningeal thickening 2 / 7739
58
(HPO:0000238) Hydrocephalus 278 / 7739
59
(OMIM) Muscle biopsy shows decreased glycosylation of alpha-dystroglycan 9 / 7739
60
(OMIM) Contractures, progressive 1 / 7739
61
(HPO:0000007) Autosomal recessive inheritance 2538 / 7739
62
(OMIM) Hypo- or areflexia 4 / 7739

Associated genes:

ClinVar (via SNiPA)

Gene symbol Variation Clinical significance Reference

Additional Information:

Description: (OMIM) MDDGA4 is a severe autosomal recessive muscular dystrophy-dystroglycanopathy with characteristic brain and eye malformations, seizures, and mental retardation. Cardiac involvement in FCMD/MEB occurs in the second decade of life in those who survive. FKTN-related Walker-Warburg syndrome is a ...
Clinical Description OMIM This disorder has been described as FCMD/muscle-eye-brain disease (MEB) and the more severe Walker-Warburg syndrome; these designations have been retained here when used in the literature.

- Fukuyama Congenital Muscular Dystrophy/FKTN-Related Muscle-Eye-Brain Disease

Fukuyama ...

Genotype-Phenotype Correlations OMIM Kondo-Iida et al. (1999) noted that the frequency of severe phenotypes, including Walker-Warburg syndrome-like manifestations such as hydrocephalus and microphthalmia, was significantly higher among probands who were compound heterozygotes carrying a point mutation on one allele and a ...
Molecular genetics OMIM Kobayashi et al. (1998) described a haplotype that is shared by more than 80% of FCMD chromosomes, indicating that most chromosomes bearing the FCMD mutation could be derived from a single ancestor. They reported that there is a ...
Population genetics OMIM Kobayashi et al. (1998) reported that the retroposon sequence insertion (607440.0001) was found in 125 of 144 (87%) FCMD chromosomes, whereas it was found in only 1 of 176 chromosomes in unrelated normal individuals; the frequency of 1 ...
Diagnosis GeneReviews The diagnosis of Fukuyama congenital muscular dystrophy (FCMD) is suspected in individuals with the following findings [Fukuyama et al 1960, Fukuyama et al 1981, Osawa et al 1997, Saito & Kobayashi 2001]:...
Clinical Description GeneReviews Fukuyama congenital muscular dystrophy (FCMD) is characterized by dystrophic changes in the skeletal muscle and by CNS migration disturbances resulting in cerebral and cerebellar cortical dysplasia. The clinical features are hypotonia, weakness, and psychomotor retardation. Mild, typical, and severe phenotypes are recognized. The phenotypic spectrum ranges from a Walker-Warburg syndrome (WWS)-like phenotype at the severe end [Chang et al 2009] to a limb-girdle muscular dystrophy-like phenotype at the mild end [Akiyama et al 2006, Godfrey et al 2006, Godfrey et al 2007, Puckett et al 2009]....
Genotype-Phenotype Correlations GeneReviews Haplotype analysis. Saito et al [2000a] used microsatellite markers closest to FKTN for haplotype analysis of 56 Japanese families, including 35 families with a typical phenotype, 12 families with a mild phenotype, and nine families with a severe phenotype. In total, 38 of 56 families were homozygous for the ancestral haplotype, including 27 of the 35 families with a typical phenotype:...
Differential Diagnosis GeneReviews Fukuyama congenital muscular dystrophy (FCMD) is one of the congenital muscular dystrophies, a clinically and genetically heterogeneous group of inherited muscle disorders, characterized by muscle weakness evident at birth or in early infancy. The main congenital muscular dystrophy (CMD) subtypes are laminin alpha-2 (merosin) deficiency (MDC1A), collagen VI-deficient CMD, the dystroglycanopathies (caused by mutations in POMT1, POMT2, FKTN, FKRP, LARGE, and POMGNT1), SEPN1-related CMD (previously known as rigid spine syndrome, RSMD1) and LMNA-related CMD (L-CMD). (See Congenital Muscular Dystrophy Overview). ...
Management GeneReviews To establish the extent of disease in an individual diagnosed with Fukuyama congenital muscular dystrophy (FCMD), the following evaluations are recommended:...
Molecular genetics GeneReviews Information in the Molecular Genetics and OMIM tables may differ from that elsewhere in the GeneReview: tables may contain more recent information. —ED....