Amniotic band sequence in paternal half‐siblings with vascular Ehlers–Danlos syndrome

Abstract

Familial amniotic band sequence (ABS) is rare but has been reported in the offspring of mothers with connective tissue disorders. We present a family of two half‐siblings with ABS who share the same biological father. Following a serious vascular event a de novo pathogenic variant in COL3A1 was detected in the father, confirming a diagnosis of vascular Ehlers–Danlos syndrome (vEDS). The same variant was found in both his ABS‐affected children but not in his unaffected child. The amniotic membrane is derived from fetal tissue, type III collagen being a component. As the affected children are paternal half‐siblings, ABS was less likely due to maternal factors. Rather, the amniotic bands may have resulted from decreased type III collagen production as seen in people with vEDS, causing fragility of the amniotic membrane. Consequently, it is important to consider vEDS in patients with ABS.

Inherited cause of in utero digital malformations

“…The correlation between an underlying connective tissue disorder and ABS has been widely accepted in general knowledge, but there have been few cases reported and limited research on this topic. After an extensive review of the literature, we believe that this is the third reported case of paternally inherited vEDS associated with ABS 7. These authors reported two paternal half-siblings with ABS who shared with their father the same pathogenic variant in COL3A1.…”

Diagnostic Clue in a Neonate with Amniotic Band Sequence

“…In this study, the prevalence of ABS in the general US population was given as 7 in 10,000 (0.07%), based on CDC data, whereas the prevalence in a cohort of vEDS patients was found to be 5 in 1,231 (0.4%) [ 7 ]. These data suggested that those with vEDS hold a five-fold greater risk of developing ABS relative to a control population [ 8 ]. Moreover, the recent case of two step-siblings who presented with ABS at birth was reported.…”

“…The children had different mothers and shared a father who was suffering from vEDS. A variant of the COL3A1 gene is documented in vEDS in which lysine is replaced by glutamic acid; the result is a reduced production of collagen type III, which causes fragility of the amniotic membrane [ 8 ].…”

The dysmorphic phenotype in vascular Ehlers Danlos syndrome

“…Amniotic bands occur in around 1% of pregnancies with vEDS. The amniotic membrane contains type III collagen so weakening of this is most likely the mechanism (Callaghan et al, 2020). Most cases have features consistent with any anatomical amniotic band formation, but distal limb abnormalities appear most frequently.…”