Autosomal recessive limb-girdle muscular dystrophy type 2I

General Information (adopted from Orphanet):

Synonyms, Signs: MDDGC5
LGMD2I
Limb girdle muscular dystrophy due to FKRP deficiency
Muscular dystrophy-dystroglycanopathy, limb-girdle, FRKP-related
Muscular dystrophy, limb-girdle, type 2I
Number of Symptoms 39
OrphanetNr: 34515
OMIM Id: 607155
ICD-10: G71.0
UMLs:
MeSH:
MedDRA:
Snomed:

Prevalence, inheritance and age of onset:

Prevalence: < 9 of 100 000
Inheritance: Autosomal recessive
24843229 [IBIS]
Age of onset: Childhood
Adolescent
Adult
16344347 [IBIS]

Disease classification (adopted from Orphanet):

Parent Diseases: Autosomal recessive limb-girdle muscular dystrophy
 -Rare genetic disease
 -Rare neurologic disease
Congenital disorder of glycosylation with neurological involvement
 -Rare genetic disease
 -Rare neurologic disease
Disorder of O-mannosylglycan synthesis
 -Rare genetic disease
Qualitative or quantitative defects of FKRP
 -Rare genetic disease

Comment:

LGMD2I is an autosomal recessive disease caused most frequently by a homozygous founder mutation (c.826C>A) in the fukutin-related protein gene (FKRP) (PMID:24843229). There was no absolute correlation between skeletal muscle weakness and cardiomyopathy or respiratory insufficiency (PMID:15505776).

Symptom Information: Sort by abundance 

1
 (HPO:0002460) Distal muscle weakness Occasional [IBIS] 25% (n=20) 16344347 IBIS 122 / 7739
2
 (HPO:0003701) Proximal muscle weakness Very frequent [IBIS] 16344347 IBIS 105 / 7739
3
 (HPO:0008994) Proximal muscle weakness in lower limbs Frequent [IBIS] 35% (n=20) 16344347 IBIS 11 / 7739
4
 (HPO:0003749) Pelvic girdle muscle weakness Very frequent [IBIS] 16344347 IBIS 15 / 7739
5
 (HPO:0003547) Shoulder girdle muscle weakness 16344347 IBIS 21 / 7739
6
 (HPO:0003691) Scapular winging Occasional [IBIS] 15% (n=20) 16344347 IBIS 51 / 7739
7
 (HPO:0002515) Waddling gait 16344347 IBIS 56 / 7739
8
 (HPO:0002355) Difficulty walking 16344347 IBIS 61 / 7739
9
 (HPO:0009046) Difficulty running Occasional [IBIS] 21% (n=38) 24587344 IBIS 17 / 7739
10
 (HPO:0003551) Difficulty climbing stairs Occasional [IBIS] 28% (n=38) 24587344 IBIS 23 / 7739
11
 (HPO:0002359) Frequent falls 24587344 IBIS 24 / 7739
12
 (HPO:0002948) Vertebral fusion 14523375 IBIS 28 / 7739
13
 (HPO:0001771) Achilles tendon contracture 12666124 IBIS 27 / 7739
14
 (HPO:0002650) Scoliosis 16344347 IBIS 705 / 7739
15
 (HPO:0002808) Kyphosis 14523375 IBIS 289 / 7739
16
 (HPO:0012548) Fatty replacement of skeletal muscle 24587344 IBIS 8 / 7739
17
 (HPO:0003712) Skeletal muscle hypertrophy 16344347 IBIS 42 / 7739
18
 (HPO:0008981) Calf muscle hypertrophy 16344347 IBIS 28 / 7739
19
 (HPO:0000158) Macroglossia Occasional [IBIS] 15% (n=20) 16344347 IBIS 119 / 7739
20
 (HPO:0003733) Thigh hypertrophy 24587344 IBIS 2 / 7739
21
 (HPO:0003307) Hyperlordosis 16344347 IBIS 122 / 7739
22
 (HPO:0003115) Abnormal EKG 15505776 IBIS 44 / 7739
23
 (HPO:0001638) Cardiomyopathy Frequent [IBIS] 42% (n=38) 24587344 IBIS 192 / 7739
24
 (HPO:0001635) Congestive heart failure Occasional [IBIS] 24% (n=38) 15505776 IBIS 232 / 7739
25
 (HPO:0012664) Reduced ejection fraction Frequent [IBIS] 60% (n=23) 18639457 IBIS 32 / 7739
26
 (HPO:0005162) Left ventricular failure 15505776 IBIS 18 / 7739
27
 (HPO:0001644) Dilated cardiomyopathy 16344347 IBIS 141 / 7739
28
 (HPO:0003236) Elevated serum creatine phosphokinase 16344347 IBIS 214 / 7739
29
 (HPO:0002111) Restrictive deficit on pulmonary function testing 16344347 IBIS 25 / 7739
30
 (HPO:0002792) Reduced vital capacity Frequent [IBIS] 75% (n=12) 16344347 IBIS 17 / 7739
31
 (HPO:0002877) Nocturnal hypoventilation 15505776 IBIS 9 / 7739
32
 (HPO:0008305) Exercise-induced myoglobinuria 25% [HPO:probinson] 22029705 IBIS 7 / 7739
33
 (HPO:0003326) Myalgia Occasional [IBIS] 10% (n=20) 16344347 IBIS 143 / 7739
34
 (HPO:0003394) Muscle cramps 24587344 IBIS 106 / 7739
35
 (HPO:0003741) Congenital muscular dystrophy 16344347 IBIS 22 / 7739
36
 (HPO:0003560) Muscular dystrophy 16344347 IBIS 88 / 7739
37
 (HPO:0003828) Variable expressivity 16344347 IBIS 130 / 7739
38
 (HPO:0040083) Toe walking 24587344 IBIS 15 / 7739
39
 (HPO:0030099) Reduced muscle fiber alpha dystroglycan Frequent [IBIS] 16344347 IBIS 2 / 7739

Associated genes:

FKRP;

ClinVar (via SNiPA)

Gene symbol Variation Clinical significance Reference

Additional Information:

Description: (OMIM) MDGDC5 is an autosomal recessive muscular dystrophy characterized by variable age at onset, normal cognition, and no structural brain changes (Brockington et al., 2001). It is part of a group of similar disorders resulting from defective glycosylation of ...
Clinical Description OMIM Bushby et al. (1998) described 7 patients, including 2 sib pairs, with a late-onset limb-girdle muscular dystrophy. Apart from 1 patient, whose muscle problems began in childhood, the age at onset ranged from 17 to 40 years. The ...
Genotype-Phenotype Correlations OMIM Sveen et al. (2006) identified FKRP mutations in 38 of 99 Danish individuals with a clinical diagnosis of LGMD2, making LGMD2I the most common LGMD subtype in this country. Of the 38 individuals, 27 were homozygous for L276I, ...
Molecular genetics OMIM In 17 families with LGMD2I, Brockington et al. (2001) identified several mutations in the FKRP gene. Affected individuals from 15 of the 17 families had an identical L276I (606596.0004) mutation; individuals in 5 families were homozygous for this ...