Characteristically exhibiting in the big toe at birth, it causes the formation of heterotopic bone throughout the body over the course of the sufferers life, causing chronic pain and eventually leading to the immobilisation and fusion of most of the skeleton by abnormal growths of bone.Another rare genetic disorder causing heterotopic ossification is progressive osseous heteroplasia (POH), is a condition characterized by cutaneous or subcutaneous ossification. Diagnosis
During the early stage, an x-ray will not be helpful because there is no calcium in the matrix. (In an acute episode which is not treated, it will be 3– 4 weeks after onset before the x-ray is positive.) Early laboratory tests are not very helpful. Alkaline phosphatase will be elevated at some point, but initially may be only slightly elevated, rising later to a high value for a short time. Unless weekly tests are done, this peak value may not be detected. It is not useful in patients who have had fractures or spine fusion recently, as they will cause elevations.The only definitive diagnostic test in the early acute stage is a bone scan, which will show heterotopic ossification 7 – 10 days earlier than an x-ray. The three-phase bone scan may be the most sensitive method of detecting early heterotopic bone formation. However, an abnormality detected in the early phase may not progress to the formation of heterotopic bone.
During this age bracket, truncal obesity can develop, characterized by the buildup of fat around ones trunk or torso as opposed to the persons extremities. Males enter puberty at around age twelve and develop normally, except for their penis, which will remain at the prepubescent size, resulting in a micropenis. Both the life span and fertility of individuals with MORM syndrome is unclear . Genetic
MORM syndrome is associated with the gene INPP5E. INPP5E is a gene whose function is not well understood. It is hypothesized to play a role in primary cilia stability. A homozygous mutation in the INPP5E gene, on chromosome 9q34, is the cause for MORM syndrome. The mutation causes a homozygous transition in the last exon of the INPP5E gene. This transition results in the DNA bases changing from a cytosine residue to a thymine residue. The resulting protein will then have an altered amino acid sequence. In unaffected individuals this specific codon (region of DNA bases) is supposed to code for the amino acid glutamine. In cases of MORM syndrome this codon codes for a termination sequence, which prematurely stops the production of the protein. In unaffected individuals the protein is evenly disbursed throughout the cilia axoneme, which stabilizes the cilia, which are antenna like structures which protrude from the extracellular surface of the cell. They play an important role in extracellular signalling/communication between cells and their environment.