PRIMEVIEW

THE EHLERS−DANLOS SYNDROMES

Most types of EDS are inherited in an autosomal dominant For the Primer, visit doi:10.1038/s41572-020-0194-9
manner, although some cases can arise owing to de novo
mutations or are inherited in a recessive manner MANAGEMENT
The Ehlers−Danlos syndromes (EDS) /'%*#0+5/5
are a group of connective tissue
disorders caused by alterations in genes
All patients with EDS should receive multi-
encoding fibrillar collagens, collagen
disciplinary care and, if available, be part of
modifying or collagen-
Variants a patient advocacy community. The precise
processing enzymes, or
in genes treatment depends upon the subtype of EDS
enzymes that modify
encoding the fibrillar and its manifestations. Physiotherapy is essential
glycosaminoglycans
procollagens I, III and for patients with musculoskeletal alterations.
within the extracellular
V, or in genes encoding Helmets and/or skin protection, or joint protection,
OCVTKZ| '%/ 
enzymes responsible for braces or splints can be used to reduce the risk
cleaving procollagen to of injury in patients with skin fragility or joint
OCVWTGEQNNCIGPNGCFVQ ER Golgi hypermobility. In addition, low-resistance exercise
DIAGNOSIS collagen fibrils with an (such as walking or swimming) can improve joint
CDPQTOCNUVTWEVWTGQT stability, although exercise that place considerable
The symptoms of EDS are composition strain on the joints (such as gymnastics or weight
diverse and differ between lifting) should be avoided. Monitoring for
subtypes. Symptoms that cardiovascular alterations using non-
Variants
are found in multiple EDS subtypes include joint invasive procedures is recommended
%NGCXCIGGP\[OG in genes
hypermobility, soft and hyperextensible skin, poor in patients at risk of adverse
involved in
wound healing, pain and easy bruising. Vascular Procollagen cardiovascular events.
EQNNCIGPETQUUNKPMKPI
and musculoskeletal symptoms are present in #EEWTCVGFCVCQP and collagen folding
some subtypes. Diagnostic work-up comprises the prevalence ECWUGUKORCKTGF
clinical examination, followed by genetic testing and incidence of EDS collagen
in individuals who fulfil the clinical criteria for an CTGPQV|CXCKNCDNG Collagen
ETQUUNKPMKPI
EDS subtype. Genetic testing can include targeted
analysis in those with a family history of EDS caused
by a known genetic variant or, more frequently,
next-generation sequencing using multi- Collagen
Variants ȮDTKN
gene panels. Genetic diagnosis should
in genes
lead to family testing to enable
encoding ECM
detection of EDS in family members DTKFIKPIOQNGEWNGUQT
and, for patients with a recessive form in enzymes that modify OUTLOOK
of EDS, carrier testing in their partners ECM proteoglycans
to evaluate the risk of transmission can interfere with the
to offspring. Of note, the genetic Despite improvements in genetic testing, some
organization of forms of EDS (hypermobile EDS) and some
cause of hypermobile EDS has not been collagen fibrils Bridging
determined and, therefore, OQNGEWNGU Other patients with other forms of EDS have
variants, PQKFGPVKȮGFIGPGVKEECWUGYJKEJECP
diagnosis of this condition
UWEJCUVJQUG hinder diagnosis of these conditions.
is based on the
in the complement .CTIGUECNGKPVGTPCVKQPCNUVWFKGU
presence of clinical Proteoglycans CTGWPFGTYC[VQCFFTGUUVJKUKUUWG
manifestations pathway and in genes of
WPMPQYPKPVTCEGNNWNCT Genotype−phenotype correlations
only. for EDS are only starting to emerge;
HWPEVKQPECPECWUG
rarer forms additional correlations may be
QH|'&5 KFGPVKȮGFD[QPIQKPI|TGUGCTEJ

doi:10.1038/s41572-020-0206-9; Article citation ID: (2020) 6:63 Written by Louise Adams; designed by Laura Marshall
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