title: Distal arthrogryposis: clinical and genetic findings.
abstract: OBJECTIVE
  Distal arthrogryposis is characterized by congenital contractures predominantly in hands and feet. Mutations in sarcomeric protein genes are involved in several types of distal arthrogryposis. Our aim is to describe clinical and molecular genetic findings in individuals with distal arthrogryposis and evaluate the genotype-phenotype correlation.
  
  
  METHODS
  We investigated 39 patients from 21 families. Clinical history, including neonatal findings, joint involvement and motor function, was documented. Clinical examination was performed including evaluation of muscle strength. Molecular genetic investigations were carried out in 19 index cases. Muscle biopsies from 17 patients were analysed.
  
  
  RESULTS
  A pathogenic mutation was found in six families with 19 affected family members with autosomal dominant inheritance and in one child with sporadic occurrence. In three families and in one child with sporadic form, the identified mutation was de novo. Muscle weakness was found in 17 patients. Ambulation was affected in four patients and hand function in 28. Fourteen patients reported pain related to muscle and joint affection.
  
  
  CONCLUSIONS
  The clinical findings were highly variable between families and also within families. Mutations in the same gene were found in different syndromes suggesting varying clinical penetrance and expression, and different gene mutations were found in the same clinical syndrome demonstrating genetic heterogeneity.
authors.affiliation: Department of Women's and Children's Health, Uppsala University Children's Hospital, Uppsala, Sweden.
authors.forename: Eva
authors.initials: E
authors.lastname: Kimber
authors.forename: Homa
authors.initials: H
authors.lastname: Tajsharghi
authors.forename: Anna-Karin
authors.initials: AK
authors.lastname: Kroksmark
authors.forename: Anders
authors.initials: A
authors.lastname: Oldfors
authors.forename: Már
authors.initials: M
authors.lastname: Tulinius
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D054458:Amplified Fragment Length Polymorphism Analysis; D001176:Arthrogryposis / Q000235:genetics / Q000473:pathology / Q000503:physiopathology; D001706:Biopsy; D002648:Child; D002675:Child, Preschool; D003598:Cytoskeletal Proteins / Q000235:genetics*; D005260:Female; D056726:Genetic Association Studies; D005819:Genetic Markers; D006801:Humans; D007223:Infant; D008297:Male; D008875:Middle Aged; D009048:Motor Skills; D018908:Muscle Weakness / Q000209:etiology; D018482:Muscle, Skeletal / Q000473:pathology / Q000503:physiopathology; D059352:Musculoskeletal Pain / Q000209:etiology; D012150:Polymorphism, Restriction Fragment Length; D013548:Sweden; D014335:Tropomyosin / Q000235:genetics*; D019210:Troponin I / Q000235:genetics*; D055815:Young Adult
chemical_list: D003598:Cytoskeletal Proteins; D005819:Genetic Markers; C510594:MYH3 polypeptide, human; C518658:TNNI2 protein, human; C518659:TPM2 protein, human; D014335:Tropomyosin; D019210:Troponin I