Multiple pterygium, Escobar and related syndromes panel [15 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.
Priority Genes : Genes where there is sufficient evidence (clinical and functional) to consider them associated with the disease; they are included in the clinical practice guidelines.
Secondary Genes: Genes related to the disease, but with a lower level of evidence or that constitute sporadic cases.
* Candidate Genes: Not enough evidence in humans, but potentially associated with the disease.
- Dimitraki M, Tsikouras P, Bouchlariotou S, Dafopoulos A, Konstantou E, Liberis V. Prenatal assessment of arthrogryposis. A review of the literature. J Matern Fetal Neonatal Med. 2011 Jan;24(1):32-6.
- Hall JG. Arthrogryposis (multiple congenital contractures): diagnostic approach to etiology, classification, genetics, and general principles. Eur J Med Genet. 2014 Aug;57(8):464-72.
- Lowry RB, Sibbald B, Bedard T, Hall JG. Prevalence of multiple congenital contractures including arthrogryposis multiplex congenita in Alberta, Canada, and a strategy for classification and coding. Birth Defects Res A Clin Mol Teratol. 2010 Dec;88(12):1057-61.
- Darras BT, Menache-Stroninki CC, Hinton V, Kunkel LM. Neuromuscular Disorders of Infancy, Childhood and Adolescence: A Clinician’s Approach, 2nd ed, Darras BT, Jones HR Jr, Ryan MM, De Vivo DC (Eds), Academic Press, San Diego 2015.