Kyphoscoliotic Ehlers-Danlos syndrome (Version 1.4)

Note: This panel has been superseded by Ehlers-Danlos syndromes panel.

Inclusion Criteria
Presumed Kyphoscoliotic Ehlers Danlos Syndrome with no genetic diagnosis with two or more of the following features:
•	Significant Joint hypermobility and dislocations
•	Skin fragility and hyperextensibility
•	Kyphoscoliosis
•	Increased length at birth with wrist drop
•	Muscular hypotonia
•	Criss-cross lines on palm and soles
•	Hearing impairment
•	Ocular fragility

Exclusion Criteria
•	Known genetic aetiology
•	Kyphoscoliosis as part of an underlying genetic / syndromal diagnosis
•	Symptomatic joint hypermobility without additional confirmed diagnostic features such as kyphoscoliosis

Prior Genetic Testing:
- Results should have been reviewed for all genetic tests undertaken. This includes review of available exome sequencing data, but where this is the case can be limited to genes specified within disease-relevant in silico panels. The patient is not eligible if a pathogenic variant has been identified in any gene related to their phenotype.
- Standard local genetic testing and nationally commissioned testing for this phenotype should have been completed AND
- Testing should be undertaken for any individual gene for which diagnostic yield is >10% for this phenotype AND
- The following specific gene tests are advised as a means of limiting the re-discovery of recognised pathogenic variants that could be more efficiently identified through the existing catalogue of UKGTN tests:
•	PLOD1
•	If seen in Specialist EDS Centres (London/ Sheffield): Kyphoscoliotic targeted gene panel

These requirements will be kept under continual review during the main programme and may be subject to change.