Genetics

• Ollier's disease (and Maffucci's syndrome) are usually non-familial disorders. Both disorders thus appear to occur spontaneously and are not inherited.^[1]
• Although an identical heterozygous mutation in the PTHR1 gene has been identified, other mutations in this gene were not identified in additional patients with this disorder. These studies suggest that the cause of Ollier's disease is heterogeneous and raise the possibility that two (or more) genetic mutations are required to develop the disease. The development of enchondromas could thus be caused by a germ line mutation associated with a somatic mosaic mutation.^[1]
• Additional mutational events may underlie progression from enchondromas to tumours.^[1]

Epidemiology

• Ollier's disease is very rare. The estimated prevalence of Ollier's disease is 1/100,000.^[1]
• Maffucci's syndrome is even rarer.
• Solitary endochondromas are most commonly discovered between 20 and 40 years of age but Ollier's disease tends to present before the age of 10 years.
• Boys are affected twice as often as girls.

Classification

There are 6 types of enchondromatosis but 3 are more common.

• In Ollier's disease there are multiple enchondromas that are mostly unilateral or unevenly distributed throughout the metaphases of the long bones, sparing the cranium and spine.
• In Maffucci's syndrome the enchondromas occur with multiple cutaneous haemangiomas that appear as soft tissue calcifications or phleboliths on X-ray.
• If there is symmetrical involvement throughout the body, including the cranium, hands and feet, it is known as generalised enchondromatosis.

Presentation

The lesions of Ollier's disease tend to be bilateral but to predominate on one side. Enchondromas usually occur in the short tubular bones of the hands and feet as well as long bones of upper and lower extremities. Palpable masses develop that may cause angular deformity and asymmetrical growth. The masses increase in size as the child grows along with asymmetrical shortening of a limb and either genu varus or genu valgus deformities. Varus deformity is very common.^[2]

Differential diagnosis

The differential diagnosis may include:

• Hereditary multiple endochondromatosis (HME). HME is an autosomal dominant disorder characterised by multiple bone tumours capped by cartilage, that occur mostly in the metaphyses of long bones.^[1]
• Other rare forms of chondromatosis (which include metachondromatosis, spondyloenchondroplasia and genochondromatosis types I and II).^[1]
• Polyostotic fibrous dysplasia.
• Diaphyseal aclasis.
• Kaposi's sarcoma.
• Klippel-Trénaunay-Weber syndrome.

Investigations

• The basic investigation is X-ray. Most cases have diaphyseal or metaphyseal lesions which do not cross the growth plate until after it has closed. Sometimes enchondromatosis will affect the metaphyseal and epiphyseal regions. When enchondromas cross the growth plate they cause severe limb length deformities and angular deformities.
• CT or MRI scanning may be required, as may bone scans. They are indicated for the evaluation and surveillance of lesions that become symptomatic (pain, and increase in size).^[1]
• Biopsy of suspicious lesions may be required.

Management

The most common difficulties experienced with Ollier's disease concern mobility and hand function. These difficulties are managed with physiotherapy and orthotics.

Serial surgery may be required for the distortion of joints and when limbs are of unequal lengths.^{[2][3][4][5][6]}

Complications

As well as the problem of asymmetrical growth there can be pathological fracture and malignant change.

In Ollier's disease very variable rates of malignant change have been reported.^[7] In Maffucci's syndrome there is a greater risk of malignant change. A study from the Mayo Clinic reviewed 55 cases between 1907 and 1985.^[8] This study from a specialist centre gives results which are likely to be misleading for the majority of patients.

Prognosis

• The prognosis for Ollier's disease is difficult to assess as there is a paucity of peer-reviewed research and much of it is contradictory.
• As is generally the case, forms with an early onset appear more severe.^[1]
• The reported incidence of malignant transformation is variable and estimated to occur in 5-50%.^[1]

Prevention

Despite acceptance that Ollier's disease carries a risk of malignant change there is little in the literature to quantify the risk and no agreed protocol for screening.

History

Louis Xavier Édouard Léopold Ollier was a French surgeon who was born in 1830 and died in 1900. He was an intern of Lyon Hospital in 1851, graduated in medicine with distinction in 1856 and, in 1857, obtained his doctorate at Paris with a dissertation based on histological studies of 400 malignant neoplasms. His most notable work was in bone and joint surgery. In 1877 a new medical faculty was established in Lyon and he was appointed professor of clinical surgery.

Angelo Maffucci was an Italian pathologist who was born in 1847 and died in 1903. He graduated in Naples in 1872. In 1882 he became head of general pathology at Messina University and the following year he received the chair of anatomical pathology at Catania. In 1884 he was appointed to the chair of pathological anatomy in Pisa, where he died in 1903. He made considerable contributions that were poorly recognised outside Italy.