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

• Published in: Clinical genetics Vol. 63; no. 3; pp. 224 - 227
• Main Authors: Kroes, HY, Pals, G, Van Essen, AJ
• Format: Journal Article
• Language: English
• Published: Oxford, UK Munksgaard International Publishers 01.03.2003; Blackwell
• Subjects: amniotic band disruption sequence; Biological and medical sciences; COL3A1; collagen protein profile; Collagen Type III - genetics; Ehlers-Danlos Syndrome - genetics; Ehlers-Danlos Syndrome - pathology; Ehlers-Danlos syndrome type IV; Electrophoresis, Polyacrylamide Gel; esophageal atresia; Female; Fibroblasts - chemistry; Humans; hydrocephaly; Male; Medical sciences; Point Mutation; Sarcoidosis. Granulomatous diseases of unproved etiology. Connective tissue diseases. Elastic tissue diseases. Vasculitis; Sequence Analysis, DNA; Skin disease; Pathogenesis; Esophageal disease; Diseases of the osteoarticular system; Lower limb; Genetic determinism; Clubfoot; Gene; Ehlers Danlos syndrome; Systemic disease; Disease of the foot; Atresia; Hydrocephaly; collagen protein profile; esophageal atresia; Human; Nervous system diseases; Elastic tissue disease; Family study; Ehlers-Danlos syndrome type IV; Clinical form; Congenital disease; amniotic band disruption sequence; Cerebral disorder; Genetic disease; Esophagus; Case study; COL3A1; Malformation; Collagen; Central nervous system disease; Digestive diseases; Atypical; Mutation; Macrocephaly
• ISSN: 0009-9163; 1399-0004
• DOI: 10.1034/j.1399-0004.2003.00047.x

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.