Congenital muscular dystrophies with cognitive impairment. A population study.
BACKGROUND
Cognitive impairment has been reported in a significant proportion of patients with congenital muscular dystrophies (CMD), generally associated with brain changes.


OBJECTIVE
The aim of this study was to establish 1) the overall prevalence of CMD and cognitive impairment in the Italian population; 2) the frequency of individual genetically defined forms; and 3) the presence of distinct phenotypes not associated with mutations in the known genes.


METHODS
We included all patients with CMD and cognitive impairment followed in all the Italian tertiary neuromuscular centers. Clinical, brain MRI, and morphologic data were collected. Genetic screening of the known genes was performed according to clinical and muscle biopsy findings.


RESULTS
Ninety-two of the 160 (58%) patients with CMD followed in our centers had cognitive impairment. alpha-Dystroglycan (alpha-DG) reduction on muscle biopsy was found in 73/92 (79%), with 42/73 carrying mutations in the known genes. Another 6/92 (7%) showed a laminin alpha2 deficiency on muscle biopsy and 5 of the 6 carried mutations in LAMA2. The remaining 13/92 (14%) patients had normal alpha-DG and laminin alpha2 expression on muscle.


CONCLUSIONS
This is the first population study establishing the prevalence of CMD and cognitive impairment and providing a classification on the basis of clinical, MRI, and genetic findings. We also showed that cognitive impairment was not always associated with alpha-DG or laminin alpha2 reduction or with structural brain changes.
Messina
S
S
Department of Child Neurology, Policlinico Gemelli, Catholic University, Largo Gemelli, Rome, Italy. mercuri@rm.unicatt.it
Bruno
C
C
Moroni
I
I
Pegoraro
E
E
D'Amico
A
A
Biancheri
R
R
Berardinelli
A
A
Boffi
P
P
Cassandrini
D
D
Farina
L
L
Minetti
C
C
Moggio
M
M
Mongini
T
T
Mottarelli
E
E
Pane
M
M
Pantaleoni
C
C
Pichiecchio
A
A
Pini
A
A
Ricci
E
E
Saredi
S
S
Sframeli
M
M
Tortorella
G
G
Toscano
A
A
Trevisan
C P
CP
Uggetti
C
C
Vasco
G
G
Comi
G P
GP
Santorelli
F M
FM
Bertini
E
E
Mercuri
E
E
D001921:Brain / Q000473:pathology*; D001931:Brain Mapping; D003072:Cognition Disorders / Q000453:epidemiology* / Q000235:genetics / Q000473:pathology; D015897:Comorbidity; D049030:Dystroglycans / Q000235:genetics; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D007091:Image Processing, Computer-Assisted; D007558:Italy / Q000453:epidemiology; D007797:Laminin / Q000235:genetics; D008279:Magnetic Resonance Imaging; D008297:Male; D018482:Muscle, Skeletal / Q000473:pathology; D009136:Muscular Dystrophies / Q000151:congenital* / Q000453:epidemiology* / Q000235:genetics / Q000473:pathology; D009154:Mutation; D010641:Phenotype; D015995:Prevalence
D007797:Laminin; C102645:laminin alpha 2; D049030:Dystroglycans