Arthrogryposis. Causes, Consequences and Clinical Course in Amyoplasia and Distal Arthrogryposis
Abstract
Arthrogryposis
Causes, Consequences and Clinical Course in Amyoplasia and Distal
Arthrogryposis
Background. Arthrogryposis Multiplex Congenita, AMC, is a heterogeneous
condition defined as multiple congenital joint contractures in two or more body
areas. The pathogenesis is impaired fetal movements. Amyoplasia, the most fre-
quent form, is a sporadically occurring condition with hypoplastic muscles and
joint contractures. Distal arthrogryposis (DA) syndromes are often hereditary,
and joint involvement is predominantly in hands and feet. Arhrogryposis with
CNS involvement includes chromosomal and other syndromes.
Aims. The purpose of this study was to investigate patients with arthrogrypo-
sis, to classify the different occurring forms, and to investigate causes, muscle
and joint involvement, motor function, treatment and outcome.
Methods. Patients were identified via pediatric rehabilitation centers. Family
and case history including perinatal findings were recorded. Physical investiga-
tion included joint range of motion, muscle strength and motor function. In
patients with DA molecular genetic and, in selected cases, muscle morphologic
investigations were carried out.
Results. 131 patients with arthrogryposis were investigated. The most frequent
diagnoses were amyoplasia and DA. In amyoplasia, community ambulators had
the best muscle strength, household ambulators had severe contractures in legs
but good muscle strength in arms, and non-ambulators had the most severe
contractures and muscle weakness. Muscle strength was found to be more im-
portant than joint range of motion for motor function.
In DA, muscle weakness was present in 44% of investigated patients. Mutations
in sarcomeric muscle protein genes were found in seven families with autosomal
dominant and in one child with sporadic DA. In one family with a mutation
in TNNI2 there were mild myopathic findings, in one family with mutation in
TPM2 no obvious myopathy, and in patients from three families with MYH3
mutations mild myopathic findings. Clinical findings were found to be highly
variable between families and also within families with DA.
Conclusions. Different forms of arthrogryposis were identified. In amyopla-
sia, attention should be directed at development of muscle strength with early
stimulation of active movements. Immobilisation should be minimized. DA
syndromes are clinically and genetically heterogeneous conditions. Fetal my-
opathy due to sarcomeric protein dysfunction can cause DA. An early multi-
disciplinary team evaluation for specific diagnosis and planning of treatment
is recommended.
Key words. Arthrogryposis, amyoplasia, distal arthrogryposis, muscle involve-
ment, motor function, contractures, muscle morphology, sarcomeric protein
dysfunction.
Gothenburg 2009
Parts of work
I. Kroksmark AK, Kimber E, Jerre R, Beckung E, Tulinius M: Muscle Involvement and Motor Function in Amyoplasia. Am J Med Genet A 2006;140:1757-67::PMID::16835916 II. Kimber E, Tajsharghi H, Kroksmark AK, Oldfors A, Tulinius M: A mutation in the fast skeletal muscle troponin I gene causes myopathy and distal arthrogryposis. Neurology 2006;67:597-601::PMID::16924011 III. Tajshargi H, Kimber E, Holmgren D, Tulinius M, Oldfors A: Distal arthrogryposis and muscle weakness associated with a beta-tropomyosin mutation. Neurology 2007;68:772-5::PMID:: 17339586 IV. Tajsharghi H, Kimber E, Kroksmark AK, Jerre R, Tulinius M, Oldfors A: Embryonic myosin heavy-chain mutations cause distal arthrogryposis and developmental myopathy that persists postnatally. Arch Neurol 2008;65:1083-90::PMID::18695058 V. Kimber E, Tajsharghi H, Kroksmark AK, Oldfors A, Tulinius M: Distal arthrogryposis: Clinical and genetic findings. Unpublished manuscript
Degree
Doctor of Philosophy (Medicine)
University
University of Gothenburg. Sahlgrenska Academy
Institution
Institute of Clincial Sciences. Department of Pediatrics
Disputation
Fredagen den 6 november 2009, kl.13.00, föreläsningssal 1, Drottning Silvias barn-och ungdomssjukhus, Göteborg
Date of defence
2009-11-06
eva.kimber@bredband.net
Date
2009-10-19Author
Kimber, Eva
Keywords
arthrogryposis
amyoplasia
distal arthrogryposis
muscle involvement
motor function
contractures
muscle morphology
sarcomeric protein dysfunction
Publication type
Doctoral thesis
ISBN
978-91-628-7928-0
Language
eng