Arthrogryposis extended panel [86 genes]

Arthrogryposis, or arthrogryposis multiplex congenita (AMC), is characterized by the presence of non-progressive multiple joint contractures in different areas of the body present from birth.

It is estimated that up to 1% of newborns are born with some type of congenital contracture, although the prevalence of the clinical profile of arthrogryposis multiplex congenita is estimated in 1 per 3,000 live births (Lowry et al., 2010). Approximately two thirds of affected individuals may be diagnosed by the age of two years, and great progress is being made in identifying the specific genetic and non-genetic causes of arthrogryposis (Hall et al., 2014). It has been estimated that a genetic cause can be identified in approximately 30% of cases (Dimitraki et al., 2011).

There are different forms that should be considered when selecting the genetic study:

• Amyoplasia, or “classic arthrogryposis“, makes up one third of cases, with a prevalence of 1 per 10,000 live births. They are sporadic cases, affecting all four limbs, with unaffected torso, and no multisystem involvement. Usually, they have no genetic cause, and their etiology is due to maternal-fetal factors during pregnancy. However, some forms can clinically resemble distal arthrogryposis forms, which is why it is convenient to carefully select cases based on their clinical suspicion and background before requesting a genetic study.
• Individuals with CNS involvement (malformations, intellectual disability, or other developmental) or dysmorphic traits will require an assessment that includes chromosomal and gene dosage studies (karyotype, SNP-arrays, etc.).
• Targeted genetic studies are more appropriate and have a higher yield for distal arthrogryposis and the lethal conditions associated with multiple pterygium, for which we have designed specific panels.
• It should be noted that up to 5% of arthrogryposis are secondary to myopathies and congenital myasthenic syndrome (Darras et al., 2015), which are covered from the arthrogryposis extended panel.