Bone Abstracts (2014) 3 PP388 | DOI: 10.1530/boneabs.3.PP388

Late onset presentation of osteogenesis imperfecta with additional mutation on GNAS gene: case report

Konstantinos D Stathopoulos1, Theodora Koromila2, Eleftherios P Paschalis3, Konstantinos Soultanis1, Erato Atsali1, Ilias Bournazos1, Eirini Damianou1, Aristides B Zoubos1, Panagiotis J Papaggelopoulos1 & Grigoris Skarantavos1

11st Department of Orthopedics, Bone Metabolic Unit, School of Medicine, University of Athens, Attikon’ Athens University General Hospital, Athens, Greece; 2California Technological Institute, California, USA; 3Ludwig Boltzmann Institute of Osteology, Vienna, Austria.

Aim: We present the case of a 36y female patient with multiple fragility fractures after the age of 21 and mutations in COL1A1, COL1A2 and GNAS genes.

Material and methods: A 36y female patient with multiple fractures of the axial and appendicular skeleton was referred to us for consultation. The patient was born with hexadactyly of the left foot and had a history of mild thoracolumbar scoliosis (10°) and medium height (165 cm) with no other history of medical conditions throughout childhood and adolescence. At the age of 21 she suffered a low energy fracture of her right femur and DXA scan revealed L2-L4 BMD 0.715, z-score=−3.81, Left Neck BMD 0.474, z-score=−4.2. Laboratory evaluation for bone metabolic disorders at that time was normal, the patient was diagnosed with Juvenile Osteoporosis and commenced therapy with Alendronate 10 mg per os daily and calcium/vitamin D supplementation. A year later she suffered a new fracture of her right femur, and after 2 years multiple vertebral fractures were diagnosed, followed by low energy fractures of right tibia, left femur, left shoulder and wrist. We performed laboratory examinations, peripheral quantitative computed tomography (pQCT) of the right tibia and proposed a bone biopsy as well as genetic testing for osteogenesis imperfecta and fibrous dysplasia.

Results: Bone biopsy and subsequent histomorphometry provided evidence that the patient suffered from Osteogenesis Imperfecta. Gene analysis with PCR sequencing proved that the patient was homozygous for polymorphism Sp1 and heterozygous for a Gly382Cys mutation of COL1A1, and had also the mutations Gly586Val, Gly646Cys, Gly661Ser, Gly1012Arg of COL1A2 gene, as well as the mutation R201C of GNAS gene.

Conclusion: This female patient with late-onset multiple fragility had mutations of COL1A1, COL1A2 as in osteogenesis imperfect but also of the GNAS gene, usually encountered in McCune Albright syndrome.