title: Congenital muscular dystrophies with cognitive impairment. A population study.
abstract: 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.
authors.affiliation: Department of Child Neurology, Policlinico Gemelli, Catholic University, Largo Gemelli, Rome, Italy. mercuri@rm.unicatt.it
authors.forename: S
authors.initials: S
authors.lastname: Messina
authors.forename: C
authors.initials: C
authors.lastname: Bruno
authors.forename: I
authors.initials: I
authors.lastname: Moroni
authors.forename: E
authors.initials: E
authors.lastname: Pegoraro
authors.forename: A
authors.initials: A
authors.lastname: D'Amico
authors.forename: R
authors.initials: R
authors.lastname: Biancheri
authors.forename: A
authors.initials: A
authors.lastname: Berardinelli
authors.forename: P
authors.initials: P
authors.lastname: Boffi
authors.forename: D
authors.initials: D
authors.lastname: Cassandrini
authors.forename: L
authors.initials: L
authors.lastname: Farina
authors.forename: C
authors.initials: C
authors.lastname: Minetti
authors.forename: M
authors.initials: M
authors.lastname: Moggio
authors.forename: T
authors.initials: T
authors.lastname: Mongini
authors.forename: E
authors.initials: E
authors.lastname: Mottarelli
authors.forename: M
authors.initials: M
authors.lastname: Pane
authors.forename: C
authors.initials: C
authors.lastname: Pantaleoni
authors.forename: A
authors.initials: A
authors.lastname: Pichiecchio
authors.forename: A
authors.initials: A
authors.lastname: Pini
authors.forename: E
authors.initials: E
authors.lastname: Ricci
authors.forename: S
authors.initials: S
authors.lastname: Saredi
authors.forename: M
authors.initials: M
authors.lastname: Sframeli
authors.forename: G
authors.initials: G
authors.lastname: Tortorella
authors.forename: A
authors.initials: A
authors.lastname: Toscano
authors.forename: C P
authors.initials: CP
authors.lastname: Trevisan
authors.forename: C
authors.initials: C
authors.lastname: Uggetti
authors.forename: G
authors.initials: G
authors.lastname: Vasco
authors.forename: G P
authors.initials: GP
authors.lastname: Comi
authors.forename: F M
authors.initials: FM
authors.lastname: Santorelli
authors.forename: E
authors.initials: E
authors.lastname: Bertini
authors.forename: E
authors.initials: E
authors.lastname: Mercuri
mesh_terms: 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
chemical_list: D007797:Laminin; C102645:laminin alpha 2; D049030:Dystroglycans