Spotlight on Kyphoscoliotic Ehlers-Danlos Syndrome by the EDS National Diagnostic Service – London

Spotlight on Kyphoscoliotic Ehlers-Danlos syndrome

The Ehlers-Danlos Syndromes

A total of 13 types of Ehlers-Danlos Syndromes (EDS) have been reported in recent years of which 12 have underlying genetic causes and are considered rare. Many EDS types share clinical symptoms such as unstable joints, fragility of skin and other tissues, as well as easy bruising. Specific clinical criteria have been formulated for each EDS type. However, for the rare EDS types genetic testing is required to confirm a clinical diagnosis. For hypermobile EDS or hypermobility spectrum disorder, no genetic cause(s) have been identified and so testing is not available.

What is Kyphoscoliotic Ehlers-Danlos syndrome?

Kyphoscoliotic EDS (kEDS) is a rare inherited condition caused by autosomal recessive disease-causing gene alterations in either the PLOD1 or FKBP14 gene. It affects approximately 1: 1,000,000 people. In 2017 major and minor criteria for a clinical diagnosis of kEDS were developed based on reported frequency of clinical symptoms in people with kEDS.

Major criteria were defined as:

• A low muscle tone from birth which causes significant delay in reaching motor milestones such as walking independently.
• Curvature of the spine (kyphoscoliosis) which can be present from birth or develop in young childhood and can be stable or become more severe.

Other clinical features of kEDS are defined as minor criteria (see table 1).

Table 1. Minor criteria of Kyphoscoliotic Ehlers-Danlos syndrome

Some clinical symptoms are specific to the underlying genetic cause of kEDS (see table 2).

Table 2. Gene specific minor criteria for diagnosis of Kyphoscoliotic Ehlers-Danlos syndrome

Figure 1. Symptoms of kyphoscoliotic EDS (from left to right): generalised joint hypermobility, stretchy skin, and scoliosis and kyphosis

Pictures of kyphoscoliotic EDS symptoms

Autosomal Recessive inheritance

Kyphoscoliotic EDS is, as mentioned, caused by gene alterations in the PLOD1 or FKBP14 gene. It is inherited in an autosomal recessive manner, affecting both men and women equally. Within our bodies exists two copies of our genes, with one being inherited from our mother and the other from our father. When only one gene alteration in the kEDS gene is inherited, a person is not expected to display symptoms of kEDS and is called an unaffected carrier. Despite not being affected, carriers are still able to pass on the alteration to any children they may have. If both parents are carriers of kEDS, each child will have a 1:4 (25%) chance of inheriting both the gene alterations leading to them having the condition. There is also a 1:2 (50%) chance only one copy of the alteration will be inherited resulting in them being unaffected carriers, like their parents.

Figure 2. The pattern and risk of inheritance for autosomal recessive conditions

How is Kyphoscoliotic Ehlers-Danlos syndrome managed?

Spine

• Monitoring for spinal curvature should start from early childhood to adulthood. Management of spinal curvature should be overseen by a specialist spinal orthopaedic surgeon to develop a treatment plan. Depending on the severity, surgery may be necessary

Blood vessels

• Children and adults with kEDS need to be seen regularly (for example every 5 years) by a cardiologist as they have an increased risk to develop blood vessel widening and/or rupture. This is especially important for women during pregnancy

Eyes

• Individuals should be referred to an ophthalmologist (specialist eye doctor) for assessment. Eye protection should be used where necessary
• Those with the FKBP14- related kEDS need to be seen yearly for assessment of hearing

Other

• Gentle exercise and resistance training, like swimming, can be helpful to reduce bone and joint pains. Input from health care professionals such as a physiotherapist, rheumatologist and occupational therapist may be necessary
• Therapies, such as counselling and cognitive behavioural therapy, may help with (long-term) pain management and relaxation.

Conclusion

Kyphoscoliotic EDS is a very rare, genetic type of EDS. It is important for people with kEDS to specify their type of EDS when talking to doctors as there are specific signs and symptoms in this condition that require tailored management and surveillance. Through national and international collaboration with other doctors and researchers we are aiming to learn more about this condition to improve management and treatment.

Samuel Liebert, Research Assistant &
Juliette Harris, Genetic Counsellor &
Fleur van Dijk, Consultant in Genomic Medicine,

National EDS service London

This information was provided by the NHS Ehlers Danlos Syndrome National Diagnostic Service which  is a specialist service for people with clinical features of rare EDS types. This service only accepts referrals from NHS consultants.

Ehlers Danlos National Diagnostic Service (London)
Level 8V
Northwick Park & St Marks Hospital
Watford Road
Harrow, HA1 3UJ
Telephone: 0208 869 3166
Email: lnwh-tr.EDSLondonOffice@nhs.net

December 2024