Kyphoscoliotic Ehlers-Danlos syndrome

Alternate names

EDS VIA; EDS, kyphoscoliotic type; EDS, oculoscoliotic type; Ehlers-Danlos syndrome type 6A (formerly); Ehlers-Danlos syndrome, kyphoscoliotic type; Ehlers-Danlos syndrome, oculoscoliotic type; Ehlers-danlos syndrome oculoscoliotic type; EDS 6 (formerly); Ehlers-Danlos syndrome type 6 (formerly); Ehlers-Danlos syndrome type 6A; Cutis hyperelastica; kEDS-PLOD1; Kyphoscoliotic EDS due to lysyl hydroxylase 1 deficiency; Kyphoscoliotic Ehlers-Danlos syndrome due to lysyl hydroxylase 1 deficiency; Lysyl hydroxylase-deficient EDS; Ocular-scoliotic EDS; Nevo syndrome; Ehlers-Danlos syndrome, kyphoscoliosis type; Kyphoscoliotic EDS; kEDS

Definition

Kyphoscoliotic Ehlers-Danlos syndrome is an inherited connective tissue disorder that is caused by defects in a protein called collagen.

Cause

• Kyphoscoliotic Ehlers-Danlos syndrome (EDS) is caused by changes (mutations) in the PLOD1 gene, and, rarely, in the FKBP14 gene.
• This gene gives the body instructions to make (encodes) an enzyme that helps process molecules that allow collagen to form stable interactions with one another.
• Collagen is a protein that provides structure and strength to connective tissues throughout the body.
• The FKBP14 gene encodes a protein which is a member of the FK506-binding protein family of peptidyl-prolyl cis-trans isomerases.
• The encoded protein is found in the lumen of the endoplasmic reticulum, where it is thought to accelerate protein folding.

Gene mutations

• Mutations in the PLOD1 gene lead to reduced levels of functional enzyme which disrupt networks of collagen throughout the body.
• This weakens the connective tissues and leads to the characteristic signs and symptoms associated with EDS, kyphoscoliosis type.
• It is not known how the FKBP14 gene mutations lead to the EDS.

Inheritance

Autosomal recessive inheritance, a 25% chance

Kyphoscoliotic Ehlers-Danlos syndrome is inherited in an autosomal recessive manner. This means that to be affected, a person must have a mutation in both copies of the responsible gene in each cell. The parents of an affected person usually each carry one mutated copy of the gene and are referred to as carriers. Carriers typically do not show signs or symptoms of the condition. When two carriers of an autosomal recessive condition have children, each child has a 25% chance to have the condition, a 50% chance to be a carrier like each of the parents, and a 25% chance to not have the condition and not be a carrier.

Signs and symptoms

The signs and symptoms of kyphoscoliotic EDS vary but may include:

• Hyperextensible skin that is fragile and bruises easily
• Joint hypermobility that leads to frequent dislocations and subluxations (partial dislocations)
• Severe hypotonia at birth
• Progressive kyphoscoliosis (kyphosis and scoliosis), present at birth or within the first year of life
• Scleral fragility
• Abnormal wound healing
• "Marfanoid habitus" which is characterized by long, slender fingers (arachnodactyly); unusually long limbs; and a sunken chest (pectus excavatum) or protruding chest (pectus carinatum)
• Fragile arteries that are prone to rupture
• Delayed motor development
• Unusually small corneas
• Osteopenia (low bone density)
• Congenital clubfoot
• Cardiovascular abnormalities such as mitral valve prolapse or aortic root dilatation (enlargement of the blood vessel that distributes blood from the heart to the rest of the body)

Diagnosis

A diagnosis of kyphoscoliotic Ehlers-Danlos syndrome (kEDS) is typically based on the presence of characteristic signs and symptoms. The following tests may then be recommended to confirm the diagnosis:

• Urine tests and/or a skin biopsy to detect deficiencies in certain enzymes that are important for collagen formation
• Genetic testing for changes (mutations) in the PLOD1 gene or in the FKBP14 gene.<ref>Yeowell HN, Steinmann B. PLOD1-Related Kyphoscoliotic Ehlers-Danlos Syndrome. 2000 Feb 2 [Updated 2018 Oct 18]. In: Adam MP, Ardinger HH, Pagon RA, et al., editors. GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2021. Available from: https://www.ncbi.nlm.nih.gov/books/NBK1462/</ref>[1].

Treatment

• The treatment of kyphoscoliotic Ehlers-Danlos syndrome is focused on preventing serious complications and relieving signs and symptoms.
• For example, physical therapy may be recommended in children with hypotonia and delayed motor development.
• This treatment can also help improve joint stability.
• Assistive devices such as braces may be necessary depending on the severity of joint instability.
• Depending on the severity of the kyphoscoliosis (kyphosis and scoliosis), surgery may be necessary.
• Because kyphoscoliotic EDS is associated with fragile skin with abnormal wound healing, affected people, especially children, may need to wear protective bandages or pads over exposed areas, such as the knees, shins, and forehead.
• Regular follow-up may be recommended to check for development or progression of abnormalities of the eyes, heart, and other parts of the body.

Prognosis

• The long-term outlook (prognosis) for people with kyphoscoliotic Ehlers-Danlos syndrome varies depending on the severity of the condition.
• The lifespan of affected people can be decreased, due to heart involvement and/or the potential for restrictive lung disease caused by severe kyphoscoliosis (kyphosis and scoliosis).

References

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NIH genetic and rare disease info

• NIH info on Kyphoscoliotic Ehlers-Danlos syndrome

Kyphoscoliotic Ehlers-Danlos syndrome is a rare disease.

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