Congenital Contractures NGS Panel

Turnaround Time

8 weeks

CPT Code(s)

81443

Cost

$3,000

Genes

• Arthrogryposis
• Bruck syndrome
• CAP myopathy
• Congenital Myasthenic syndrome
• Contractural arachnodactyly congenital
• Ehlers-Danlos syndrome
• Emery-Dreifuss muscular dystrophy
• Escobar syndrome
• Fetal akinesia deformation sequence
• Hyaline fibromatosis syndrome
• Lethal congenital contracture syndrome
• Marfan syndrome
• MASS syndrome
• Nemaline myopathy
• Restrictive dermopathy lethal
• Shprintzen-Goldberg syndrome
• Cerebrooculofacioskeletal syndrome
• Proximal myopathy and ophthalmoplegia
• Trismus-pseudocamptodactyly syndrome
• Congenital contractures of the limbs and face, hypotonia, and developmental delay
• Marden-Walker syndrome
• Liebenberg syndrome
• Lysyl hydroxylase 3 deficiency
• Van den Ende-Gupta syndrome
• Wieacker-Wolff syndrome
• Mandibuloacral dysplasia with type B lipodystrophy
• Congenital clubfoot with or without deficiency of long bones and/or mirror-image polydactyly

Congenital contractures are defined by constrictions or rigidity of connective tissues including muscles, ligaments, and tendons resulting in decreased range of motion and stiffness. Contractures occur in numerous genetic disorders, but the features of these syndromes vary greatly and can affect a wide variety of body systems. Treatment is symptomatic and involves physical and occupational therapy, as well as surgical correction when necessary. While over half of these conditions are inherited in an autosomal recessive manner, many phenotypes caused by changes in the same gene have been reported with either dominant or recessive inheritance. In addition, two conditions demonstrate X-linked recessive inheritance.

Next Generation Sequencing

The current design of this panel covers all genes and the flanking intronic sequences. This method allows for analysis of greater than 98% of the targeted sequence for the detection of nucleotide substitutions and small deletions and duplications. Large deletions and duplications will not be detected by this panel. Mutations and variants identified on the panel are confirmed with Sanger sequencing. All novel and apparently pathogenic changes are reported when found within the coding region as well as within 10 basepairs of each intron/exon boundary for each gene. Promoter and 3' untranslated sequences are not included in the current analysis. It should be noted that the current protocol is not specifically designed to detect copy number alterations and single exon deletions may require additional follow-up to determine whether or not they represent technical artifacts. We recommend further array-based testing to more accurately address the concerns of dosage alterations. The Cytogenetic Laboratory at GGC offers a high resolution microarray to complement the sequencing panel. The GGC Diagnostic Laboratory Directors are available for further consultation regarding the limitations of the NGS and array testing procedures.

The preferred sample type is 3-5 ml of peripheral blood collected in an EDTA (purple top) tube. Extracted DNA and saliva are also accepted for this test. Saliva samples must be submitted in an approved saliva kit. Contact the lab to receive a saliva kit or to have one sent to your patient.

The specimen should be kept at room temperature and delivered via overnight shipping. If shipment is delayed by one or two days, the specimen should be refrigerated and shipped at room temperature. Do not freeze the specimen. Samples collected on Friday can be safely designated for Monday delivery.

If the pathogenic mutation(s) are identified in an affected individual using this panel, prenatal diagnosis is available for future pregnancies. Sanger sequencing will be used for prenatal diagnosis when there is a known familial mutation. Prenatal diagnosis can also be requested when there are clincial features and ultrasound findings suggestive of a diagnosis. Additional fees for cell culture and maternal cell contamination may apply. Maternal cell contamination studies are required for all prenatal molecular tests. Contact the laboratory prior to sending a prenatal specimen.