Frequency of de novo variants and parental mosaicism in vascular Ehlers–Danlos syndrome

Legrand, Anne; Devriese, Magali; Dupuis‐Girod, Sophie; Simian, Christophe; Vénisse, Annabelle; Mazzella, Jean‐Michaël; Auribault, Karine; Adham, Salma; Frank, Michael; Albuisson, Juliette; Jeunemaı̂tre, Xavier

doi:10.1038/s41436-018-0356-2

Cited by 29 publications

(31 citation statements)

References 25 publications

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“…16,17 A recent study showed that vEDS is characterized by a high frequency of de novo pathogenic variants, while parental mosaicism was rare. 18 For women with the vascular type, pregnancy and delivery pose specific risks, which warrant preconceptional counselling with an experienced obstetrician and clinical geneticist. 19 There is considerable clinical overlap between the vascular type and Loeys-Dietz syndrome type 1 and 2 (OMIM 609192 and 610168 respectively), which are due to TGFBR1 (type 1) and TGFBR2 (type 2) mutations.…”

Section: Classification and Nosologymentioning

confidence: 99%

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Classification, nosology and diagnostics of Ehlers-Danlos syndrome

Hamel

2019

J. Biomed. Transl. Res.

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Ehlers-Danlos syndrome (EDS) comprises a group of heritable connective tissue disorders which has as cardinal features varying degrees of skin hyperextensibility, joint hypermobility, easy bruising and skin fragility. The 2017 New York nosology distinguishes 13 types of EDS, which all, except hypermobile EDS, have a known molecular basis. Hypermobile EDS is recognized as a common and often disabling disorder, incorporating benign joint hypermobility syndrome. EDS needs to be differentiated from other connective tissue disorders, in particular Marfan syndrome, Loeys-Dietz syndrome and cutis laxa. The frequent types of EDS can be diagnosed after careful history taking and clinical examination, but for definite diagnosis molecular confirmation is needed in all types. Management for EDS patients preferably is provided by multidisciplinary teams in expertise centres. After diagnosing EDS genetic counselling is an essential part of the management of patients and their family.

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Section: Classification and Nosologymentioning

confidence: 99%

“…It is important to be aware of the possibility of parental mosaicism in cases which are apparently de novo. 18…”

Section: Genetic Counsellingmentioning

confidence: 99%

Classification, nosology and diagnostics of Ehlers-Danlos syndrome

Hamel

2019

J. Biomed. Transl. Res.

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“…Vascular EDS is associated with a genetic defect in type III collagen formation localized to the COL3A1 gene on chromosome 2q32.2, which affects the synthesis, processing, and interaction of collagen with other proteins [3]. The inheritance pattern is predominantly autosomal dominant, although biallelic variants and de novo variants have been reported [4,5]. Median survival with vEDS has been reported to be 48 years, with death often occurring from rupture of major vessels or complications from intestinal perforation or uterine rupture during delivery [6,7].…”

Section: Introductionmentioning

confidence: 99%

Intestinal Perforation in Children as an Important Differential Diagnosis of Vascular Ehlers-Danlos Syndrome

2019

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Patient: Male, 6 Final Diagnosis: Colonic perforation secondary to vascular Ehlers Danlos Syndrome Symptoms: Abdominal pain • constipation Medication: — Clinical Procedure: Loop colostomy followed by total colectomy and ileostomy Specialty: Surgery Objective: Unusual clinical course Background: Ehlers-Danlos Syndrome (EDS) is a group of connective tissue disorders with heterogeneous clinical features associated with varying genetic mutations. EDS type IV, also known as vascular EDS (vEDS), is the rarest type but has fatal complications, including rupture of major vasculature and intestinal and uterine perforation. Intestinal perforation can be spontaneous or a consequence of long-standing constipation, a common symptom among patients with EDS. Case Report: We present a case of a 6-year-old boy with the previous diagnosis of vEDS who presented with colonic perforation from a stercoral ulcer. He underwent diagnostic laparoscopy and loop colostomy, with an uneventful postoperative course. Unfortunately, he developed a second colonic perforation 14 months after the initial episode and underwent total abdominal colectomy with end ileostomy. Conclusions: Intestinal perforation is a well-documented and devastating complication of vEDS. However, spontaneous intestinal perforation is extremely rare in a young child. Therefore, the diagnosis of vEDS should be included in the differential diagnosis if a child presents with intestinal perforation. There is no clear guideline available for surgical management of colonic perforation in patients with vEDS, but total abdominal colectomy appears to provide the best chance of preventing recurrent perforation.

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“…As with our patients and previous reports, NGS can be used to detect mosaicism and calculate mosaic ratios. 1,4 Previous study reported identified mosaicism in a mother of a daughter with vEDS and a son with clinically suspected vEDS. The mother of siblings had some mild clinical symptoms of vEDS: thin and translucent skin, acrogeria, easy bruising, characteristic facial appearance, hypermobility of small joints with dislocations of the thumbs, and gingival recession.…”

mentioning

confidence: 99%

“…However, mosaicism of parent is estimated to be 2% to 3%. 1 Here we reported the mosaicism of vEDS in clinically asymptomatic mother of siblings with vEDS using next generation sequencing (NGS).…”

mentioning

confidence: 99%