Endocrine Abstracts

JOINT1506

Ehlers–Danlos syndrome (EDS), osteogenesis imperfecta (OI), and cutis laxa (CL) are three rare and heterogeneous connective tissue disorders. Patients with these syndromes have similar manifestations and unpredictable prognosis, making a misdiagnosis highly probable. Osteogenesis imperfecta/Ehlers–Danlos (OI/EDS) overlap syndrome is a recently described disorder of connective tissue, characterized by mutation of COL1A1 (17q21.33) or COL1A2 (7q21.3) genes. 3-year-old boy 2nd born of a non-consanguineous parentage with no significant antenatal and neonatal complaints presented with a delay in attaining age-appropriate milestones. The child had history of recurrent fractures following trivial injuries. The first fracture occurred at the age of one year, affecting the first metacarpal bone of the right hand. The second fracture took place at one and a half years, involving the radius on the right. The third was located at the proximal phalanx of the left toe. The mother had also noted easy bruising. Failure to thrive was noted during follow up visits. Evaluation revealed short stature (85cm, -3 SDS), poor weight gain (10 kg, -3SDS). His head appeared large, he had frontal bossing, blue sclera, generalized joint laxity, hypotonia, contractures in the fingers of the left hand, and loose skin folds. His Beighton score was 7/9. Investigations done revealed normal serum calcium (2.57 mmol/l), vitamin D (147 nmol/l), alkaline phosphatase (233 IU/L) and parathormone levels (1.8 pmol/L). Other endocrinological causes of short stature were ruled out. Additionally, the DXA scan report confirmed the presence of osteoporosis (Z score -3.8 SD). Echocardiography done was normal. History of similar complaints was noted in the father, he had walked late, history of recurrent fractures and hyper mobile joints. His Beighton score was 7 out of 9. A suspicion of collagenopathy, specifically Ehlers-Danlos syndrome, osteogenesis imperfecta spectrum was raised. Whole exome sequencing done showed a pathogenic, heterozygous mutation in the COL1A2 gene on intron 9, variant c.432+1G>A which was suggestive of combined osteogenesis imperfecta and Ehlers Danlos Syndrome type 2 which has an autosomal dominant inheritance. Genetic testing of the father not done due to financial constraints. The child has been started on bisphosphonate therapy with zoledronic acid and is on regular follow up. OI/EDS overlap syndrome is a rare collagenopathy requiring high clinical suspicion for diagnosis. This case underscores the role of genetic testing in confirming the disorder, especially with a positive family history. Early bisphosphonate therapy can reduce fracture risk, thereby enhancing the quality of life for affected individuals.