IDH1 R132C and ERC2 L309I Mutations Contribute to the Development of Maffucci’s Syndrome

BackgroundMaffucci’s syndrome is characterized by the coexistence of multiple enchondromas and soft-tissue hemangiomas. It has been clear that somatic mosaic isocitrate dehydrogenase type 1 (IDH1) or isocitrate dehydrogenase type 2 (IDH2) mutations are associated with Maffucci’s syndrome and Ollier disease, but the mechanisms underlying hemangiomas of the Maffucci’s syndrome is still obscure. This study aimed to determine the mechanism of hemangiomas in Maffucci’s syndrome.MethodsWe received a 26-year-old female patient with typical Maffucci’s syndrome, and exome sequencing was conducted using DNA from her peripheral blood and enchondroma tissues. Somatic mutations were characterized by a comparative analysis of exome sequences and further confirmed by the sequencing of PCR products derived from original blood and tissue samples. The mutations of an additional 69 patients with Ollier disease were further tested. The functional impacts of these somatic mutations on Maffucci’s syndrome, especially the development of hemangiomas, were evaluated.ResultsWe reported a typical case of Maffucci’s syndrome, which was confirmed by both imaging findings and pathology. Through exome sequencing of this patient’s DNA samples, we identified an R132C mutation in the isocitrate dehydrogenase type 1 (IDH1) gene and an L309I mutation in the ELKS/RAB6-interacting/CAST family member 2 (ERC2) gene in this patient. Approximately 33.3% of the clones were positive for the IDH1 R132C mutation, and 19.0% of the clones were positive for the ECR2 L309I mutation. The IDH1 R132C mutation was detected in most of the patients with Ollier disease (51/69 patients), and the mean frequency of this mutation was 63.3% in total sequence readouts, but the ECR2 L309I mutation was absent in all of the patients with Ollier disease. In vitro experiments confirmed that the IDH1 R132C mutation promotes chondrocyte proliferation, and the ERC2 L309I mutation enhances angiogenesis.ConclusionsOur results suggest that while IDH1 is a known pathogenic gene in enchondromatosis, ERC2 is a novel gene identified in Maffucci’s syndrome. The somatic L309I mutation of ERC2 contributes to the pathogenesis of hypervascularization to facilitate the development of hemangiomas in Maffucci’s syndrome. The combination of the IDH1 R132C and ERC2 L309I mutations contributes to the development of Maffucci’s syndrome, and these results may enable further research on the pathogenesis of Maffucci’s syndrome.

Case Report: Osteomyelitis of the Proximal Phalanx of the Finger in Patient With Ollier Disease

Ollier disease is a rare congenital pathology characterized by the growth of enchondromas in bones, accompanied with their deformities, fractures, and the risk of malignancy. A 39-year-old patient with Ollier disease (acroform with lesions of hands and feet) suffered a rapid development of osteomyelitis of the proximal phalanx of the ring finger after a mosquito bite. The condition localized in the area of enchondroma. Surgical treatment included osteonecrectomy in the phalanx and enchondroma with excision of non-viable surrounding soft tissues, drainage of the surgical wound and the imposition of primary sutures. Morphological analysis confirmed the presence of ectopic embryonic cartilage specific for Ollier disease and the bone destruction. The excised tissues were infiltrated with immune cells and had signs of periosteal chronic inflammation including fibrosis and hyalinosis. These changes, which occurred long before the mosquito bite, became a favorable background for the development of a purulent infection.

Ollier disease: multiple enchondromatosis: case report and review of literature

Multiple enchondromatosis is a rare disease in which cartilage tumors appear at the level of the skeleton. The incidence is unknown due to the very few cases reported in world literature. We presented the case of a patient at the plastic surgery department at General hospital Dr. Ruben Leñero, otherwise healthy, referring first clinical manifestations at childhood with an increase in volume and deformity at the second and third fingers of the left hand.

Ollier Disease: A Case Series and Literature Review

Background. Ollier disease is the most common nonhereditary type of enchondromatosis. Enchondromas are common, usually benign intraosseous cartilaginous tumors that form near the growth plate cartilage predominantly unilaterally in the metaphyses and diaphyses of tubular bones. They usually affect the long bones of the hand, the humerus, and the tibia, followed by flat bones, such as the pelvis. The estimated prevalence of Ollier disease is 1 in 100,000 and while it is linked with somatic heterozygous mutations in IDH1 or IDH2 genes, exact etiology is unknown. The risk of malignant transformation towards chondrosarcoma is up to 30–35% and it is clinically suspected when pain and a rapid increase in the size of the lesions is seen.Case presentations. We report two clinical cases of patients diagnosed with Ollier disease. In both cases transformation to chondrosarcoma was observed.Conclusions. Ollier disease is a rare disorder, defined by the presence of multiple enchondromas and an asymmetric distribution of the cartilage lesions that can be extremely variable in terms of size, location, age, gender. Constant monitoring of patients is important due to the high risk of malignancy. Because the disease is very rare and the manifestations vary widely, each patient’s case must be evaluated, and the treatment strategy adopted individually.