pediatrics
Arthrogryposis Multiplex Congenita
Diagnosis of Arthrogryposis Multiplex Congenita
Clinical evaluation Testing for cause If a newborn has multiple contractures, the initial evaluation should determine whether the condition is amyoplasia, distal arthrogryposis, or another syndrome where multiple contractures are associated with unrelated congenital anomalies and/or metabolic disorders. When available, a clinical geneticist should coordinate the assessment and management; typically, practitioners from many specialties are involved. A syndromic form of AMC is suspected when developmental delays and/or other congenital anomalies are present, and such patients should be evaluated for central nervous system disorders and monitored for progressive neurologic symptoms. Evaluation should also include a thorough assessment for associated physical, chromosomal, and genetic abnormalities. Specific disorders to be sought include Freeman-Sheldon syndrome, Holt-Oram syndrome, Larsen syndrome, Miller syndrome, multiple pterygium syndrome, and DiGeorge syndrome (22q11 deletion syndrome). Testing typically starts with a Diagnosis followed by specific gene tests that are done individually or as a standard panel by many genetic laboratories ( In a study of 125 affected people, 43% had amyoplasia, 27% had distal arthrogryposis, and 30% had other forms ( Diagnosis references ). Combining a clinical evaluation with an AMC-specific gene panel test done by using Whole exome sequencing should be considered when other tests do not yield a definitive diagnosis, especially in familial cases ( Diagnosis references ). 1.Todd EJ, Yau KS, Ong R, et al: Next generation sequencing in a large cohort of patients presenting with neuromuscular disease before or at birth.Orphanet J Rare Dis10:148, 2015. doi: 10.1186/s13023-015-0364-0 2.Le Tanno P, Latypova X, Rendu J, et al: Diagnostic workup in children with arthrogryposis: Description of practices from a single reference centre, comparison with literature and suggestion of recommendations.J Med Genetjmedgenet-2021-107823, 2021. doi: 10.1136/jmedgenet-2021-107823 3.Pollazzon M, Caraffi SG, Faccioli S, et al: Clinical and genetic findings in a series of eight families with arthrogryposis.Genes (Basel)13(1):29, 2022. doi: 10.3390/genes13010029 4.Hunter JM, Ahearn ME, Balak CD, et al: Novel pathogenic variants and genes for myopathies identified by whole exome sequencing.Mol Genet Genomic Med3(4):283–301, 2015. doi: 10.1002/mgg3.142 