Most vEDS children diagnosed via familial genetic testing: Study
Testing recommended when family history suggests potential disorder
More than half of children with vascular Ehlers-Danlos syndrome (vEDS) are diagnosed through genetic testing after a family member is found to have the disease, a study found.
The remaining patients receive their diagnosis following a serious clinical event that requires medical intervention or due to having certain clinical features and/or a familial history suggestive of vEDS.
“Our findings emphasise the importance of offering genetic testing in childhood when there is a positive family history of vEDS and/or features suggestive of a potential inherited connective tissue disorder,” the scientists wrote.
The study, “Vascular Ehlers-Danlos syndrome in children: evaluating the importance of diagnosis and follow-up during childhood,” was published in the European Journal of Human Genetics.
Most vEDS cases are caused by mutations in the COL3A1 gene, which leads to a faulty component of type 3 collagen, a protein that gives structural support to connective tissues. In addition to the hyper-flexible joints and soft, stretchy skin that marks all types of EDS, people with vEDS have fragile arteries and internal organs, which are prone to bulging (aneurysm) or rupturing.
Diagnosing in childhood
Life-threatening events, such as severe bleeding caused by arterial ruptures or perforated intestines, typically do not occur until adulthood, which often triggers a clinical investigation. In contrast, most vEDS diagnoses made in childhood start with a positive family history.
“Little, however, has been reported on additional clinical characteristics in this young population, especially in those where diagnosis is not the result of familial testing or because of an event,” the researchers wrote.
The team, led by scientists at Imperial College London, designed a study to identify drivers of a vEDS diagnosis in children.
Data from 63 people diagnosed with vEDS in childhood were examined. Twenty were primary cases, meaning they were the first in their families to receive a diagnosis, and 40 were related to someone diagnosed with vEDS.
The team first assessed clinical events, defined as the spontaneous onset of symptoms that required specialist intervention and would not have occurred to the same degree in an unaffected individual.
A total of 13 patients had 18 events, which included intestinal perforations, bowel obstructions, spontaneous pneumothoraxes (when air leaks into the space between the lungs and chest wall, causing the lung to collapse), artery ruptures, and spleen rupture. All events required surgical intervention or repair.
Most patients had single events (69.2%), but some had two events, and one patient had three. A higher proportion of males than females had gastrointestinal perforation and collapsed lung events.
An examination of patients’ clinical characteristics found that 93.3% had one or more minor vEDS diagnostic criteria, or minor signs of vEDS, including excessive bruising (82.3%), hypermobility of the small joints (87%), thin, translucent skin (76.4%), and a characteristic facial appearance (57%). Additional clinical features included congenital heart defects, club feet, hip dislocations, and spontaneous lung collapse.
Of the 55 patients with data on birth and early development, more than half (55.4%) were born prematurely. Developmental delays requiring special care admissions were reported in 10 patients born prematurely, and these involved delays in motor development or in speech and language. Global developmental delay, which occurred in three cases, was reported in individuals with traumatic premature births.
Pathways to diagnosis
Three pathways to a vEDS diagnosis were identified: following an event, after referral for familial testing, or following investigation of specific clinical features. Among the 13 patients with a first clinical event, 11 received genetic testing following the event.
For 55.5% of the patients, diagnostic investigations were initiated due to a positive family history, and were part of familial genetic testing.
Diagnosis in those without a family history of vEDS or an event was predominantly the result of easy and/or excessive bruising (60%), in addition to one or more clinical features and/or a familial history suggestive of vEDS.
Of the 53 individuals with at least one cardiology review in childhood, 79.2% were asymptomatic, with no structural heart abnormalities identified. Over a median follow-up of 7.6 years, seven patients developed new cardiovascular abnormalities, including an aneurysm, heart valve problems, and new heart or blood vessel dilations.
Most evaluable patients (70.8%) received blood pressure-lowering medication in childhood, starting at a median age of 12.5. All individuals who experienced an event in childhood are currently taking such medications.
“We present a large clinically driven paediatric cohort reporting on features of individuals diagnosed with vEDS in childhood,” the scientists concluded. “Formal evaluation of the impact that diagnosis of vEDS in childhood has on disease management is needed when sufficient data is internationally available.”
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