Classical Ehlers-Danlos syndrome with cranio-cervical instability in an infant due to a novel COL5A1 gene mutation

Abstract

Ehlers-Danlos syndromes (EDSs) are a group of connective tissue disorders with diverse clinical and genetic profiles. Classical Ehlers-Danlos syndrome (cEDS), the second most common type, is characterised by skin hyperextensibility, atrophic scars and joint hypermobility, primarily due to mutations in COL5A1 and COL5A2 genes. We report a case of an infant with severe cEDS presenting with motor developmental delay, joint hyperextensibility and cranio-cervical instability. Genetic analysis identified a novel heterozygous missense mutation in COL5A1 (c.386G>T) and a non-segregating variant in COL1A2. The child's clinical features were more severe compared with his mother and grandmother, highlighting the variable expression of cEDS. Treatment included vitamin D and iron supplementation, physiotherapy and avoidance of excessive stretching. The child later required surgical intervention for cervical dislocation. This case emphasises the importance of clinical examination of family members and targeted genetic testing along with individualised management for severe cEDS presentations.

Keywords: Genetic screening / counselling; Pediatrics.