Ehlers–Danlos syndrome type IV: unusual congenital anomalies in a mother and son with a COL3A1 mutation and a normal collagen III protein profile

Abstract

A mother and son with Ehlers-Danlos syndrome (EDS) type IV and unusual congenital anomalies are described. The congenital anomalies include, in the mother, amniotic band-like constrictions on one hand, a unilateral clubfoot, and macrocephaly owing to normal-pressure hydrocephaly and, in the son, an esophageal atresia and hydrocephaly. Protein analysis of collagen III in cultured fibroblasts of the mother showed no abnormalities. However, DNA analysis of the COL3A1 gene revealed a pathogenic mutation (388G-->T) in both the mother and the son. The possible relationship between the observed congenital anomalies and EDS IV are discussed. We stress that DNA analysis of COL3A1 should be performed in all patients when there is a strong suspicion of EDS IV, despite negative findings in a collagen protein analysis.

Genetic Aspects of the Vascular Type of Ehlers-Danlos Syndrome (vEDS, EDSIV) in Japan

“…Tissue friability is a factor of this disease, which makes surgery technically challenging, and there is an increased risk in conducting invasive diagnostic arteriography in these patients because of the vessel friability. 17 Clinical awareness and timely diagnosis of vEDS is still inadequate, as the disease is often diagnosed only after life-threatening complications or death. 8,9,17 Complications require hospitalization and consultation with surgeons, radiologists, obstetricians and clinical geneticists.…”

“…17 Clinical awareness and timely diagnosis of vEDS is still inadequate, as the disease is often diagnosed only after life-threatening complications or death. 8,9,17 Complications require hospitalization and consultation with surgeons, radiologists, obstetricians and clinical geneticists. To improve the likelihood of a good outcome, physicians must become aware of the existence of vEDS.…”

“…To improve the likelihood of a good outcome, physicians must become aware of the existence of vEDS. 17 Improved diagnosis and establishment of both a network between the medical specialists and of long-term follow-up systems may help physicians to better manage the vascular and visceral complications associated with this disease.…”

“…7 The standard biochemical assay for vEDS may produce false-negative results because detecting a change in the protein level in all affected individuals with mutations is more difficult than in a mutation analysis. 16,17 A mutation analysis of COL3A1 is the best method available for the diagnosis of vEDS and should be performed in all affected individuals when there is suspicion of vEDS, despite negative findings in the collagen protein analysis.…”

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

“…The rheumatologist noted that the man's son had some facial features suggestive of vEDS. However, he observed that, "Whilst there are case reports of mothers with EDS having children with amniotic bands there are no cases reported of the presumed genetic defect arising from the father (Kroes et al, 2003). "…”