Occupational engagement, fatigue, and upper and lower extremity abilities in persons with melorheostosis.

INTRODUCTION: Melorheostosis is a rare bone disorder with limited literature that describes the effect of this disease on functional and motor abilities. As part of a natural history study, four outcome measures were administered to better understand the burden this disease has on a person's ability to engage in basic and instrumental activities of daily living. OBJECTIVE: To investigate the relationship between functional engagement, fatigue, and motor ability in patients with melorheostosis. DESIGN: Cross-sectional data gathered from a longitudinal natural history observational study. SETTING: Rehabilitation department within a single institution. PARTICIPANTS: Forty-seven adult volunteers with melorheostosis were enrolled. Two participants were removed for failure to meet diagnosis eligibility. Thirty patients had lower extremity (LE) osteosclerotic bone lesions, 14 had upper extremity (UE) lesions, and one had lesions in both UEs and LEs. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Activity Card Sort, Second Edition (ACS); Multi-Dimensional Fatigue Inventory; Lower Extremity Functional Scale; Upper Extremity Functional Index. RESULTS: On the ACS, high-demand leisure (HDL) activities were the least retained (p < .001). Of the activities rated most important, HDL activities were the most likely to have been given up (27%). General fatigue (µ = 11.8) and physical fatigue (µ = 11.0) were the two most limiting fatigue constructs. There were moderate negative correlations with HDL activities compared to physical fatigue (r = -0.524, p < .001) and reduced activity fatigue (r = -0.58, p = .001). LE lesions had a large effect on completing LE tasks (d = 0.95) and UE lesions had a medium effect on completing tasks involving the UE (d = 0.69). CONCLUSIONS: Patients with melorheostosis experience fatigue and low engagement in HDL activities. The results of this study underscore the importance of acknowledging activity domain, fatigue constructs, and lesion location to support and provide targeted evidence-based rehabilitative therapy. CLINICAL TRIAL REGISTRATION NUMBER: NCT02504879.

Melorheostotic Bone Lesions Caused by Somatic Mutations in MAP2K1 Have Deteriorated Microarchitecture and Periosteal Reaction.

Melorheostosis is a rare non-hereditary condition characterized by dense hyperostotic lesions with radiographic "dripping candle wax" appearance. Somatic activating mutations in MAP2K1 have recently been identified as a cause of melorheostosis. However, little is known about the development, composition, structure, and mechanical properties of the bone lesions. We performed a multi-method phenotype characterization of material properties in affected and unaffected bone biopsy samples from six melorheostosis patients with MAP2K1 mutations. On standard histology, lesions show a zone with intensively remodeled osteonal-like structure and prominent osteoid accumulation, covered by a shell formed through bone apposition, consisting of compact multi-layered lamellae oriented parallel to the periosteal surface and devoid of osteoid. Compared with unaffected bone, melorheostotic bone has lower average mineralization density measured by quantitative backscattered electron imaging (CaMean: -4.5%, p = 0.04). The lamellar portion of the lesion is even less mineralized, possibly because the newly deposited material has younger tissue age. Affected bone has higher porosity by micro-CT, due to increased tissue vascularity and elevated 2D-microporosity (osteocyte lacunar porosity: +39%, p = 0.01) determined on quantitative backscattered electron images. Furthermore, nano-indentation modulus characterizing material hardness and stiffness was strictly dependent on tissue mineralization (correlation with typical calcium concentration, CaPeak: r = 0.8984, p = 0.0150, and r = 0.9788, p = 0.0007, respectively) in both affected and unaffected bone, indicating that the surgical hardness of melorheostotic lesions results from their lamellar structure. The results suggest a model for pathophysiology of melorheostosis caused by somatic activating mutations in MAP2K1, in which the genetically induced gradual deterioration of bone microarchitecture triggers a periosteal reaction, similar to the process found to occur after bone infection or local trauma, and leads to an overall cortical outgrowth. The micromechanical properties of the lesions reflect their structural heterogeneity and correlate with local variations in mineral content, tissue age, and remodeling rates, in the same way as normal bone. © 2018 American Society for Bone and Mineral Research.

Melorheostosis: segmental osteopoikilosis or a separate entity?

PURPOSE: Melorheostosis is a progressive hyperostotic bone disease that commonly affects the appendicular skeleton. Melorheostosis has a significant degree of overlap with other hyperostosis conditions including osteopoikilosis and likely represent varying degrees of a clinical spectrum. METHODS: This is a report of 2 patients with melorheostosis who presented with different clinical presentations and involvement of different anatomic locations. RESULTS: One of the patients presented with foot size asymmetry along with intermittent foot pain and limping. This patient also had irregular nonblanching yellow plaque-like lesion on the forehead. The second patient presented with abnormal gait but no pain. Radiographs demonstrated endosteal hyperostosis, which were consistent with a mixed picture of melorheostosis and osteopoikilois. Genetic testing of the LEMD3 gene from a blood sample was negative in both cases. CONCLUSIONS: The diagnosis of melorheostosis can be made based on the clinical and radiographic features and can be challenging to differentiate from other hyperostosis conditions. LEVEL OF EVIDENCE: Level V.

Case report: severe melorheostosis involving the ipsilateral extremities.

Melorheostosis is a rare, noninheritable bone dysplasia characterized by its classic radiographic feature of flowing hyperostosis resembling dripping candle wax, generally on one side of the long bone. The condition originally was described by Leri and Joanny in 1922. Its etiology remains speculative, and treatment in most instances has been symptomatic. Melorheostosis usually affects one limb, more often the lower extremity, and rarely the axial skeleton. We report a rare case of severe melorheostosis in the ipsilateral upper and lower extremities with normal contralateral extremities. The plain radiographs revealed almost all the bones in the affected extremities, from clavicle and scapula to distal phalanges of the fingers and from femur to distal phalanges of the toes, presented extensive, dense hyperostosis and heterotopic ossification in the periarticular soft tissue. Physical examination showed considerable swelling and deformities of the left limbs, stiffness and distortion of the joints, and anesthesia in the left ulnar regions of the forearm and hand. The examination of the right side was normal. Computed tomography scans showed multiple areas of classic candle wax-like hyperostosis and narrowing or disappearance of the medullary cavity. Histologic analysis confirmed the clinical and imaging diagnosis and revealed extremely dense sclerotic bone of cortical pattern.

Lower-extremity sclerotomes: clinical applications and the modified mayo block.

A sclerotome is an anatomical concept that defines an area of bone supplied by a single spinal nerve. Similar to the familiar dermatomes, sclerotomes provide an element of depth to the sensory innervation of the lower extremity based on the deep fascia as an embryologic boundary. Anatomical knowledge of sclerotomes can be used clinically in the diagnosis and treatment of pain and in the perioperative setting. Specifically, a modified version of the classic Mayo block is presented to highlight an active anatomical approach to peripheral nerve blockade.

Spontaneous bilateral chylothorax with fatal outcome in a patient with melorheostosis.

We report a case of progressive, multifocal melorheostosis in a 28-year-old woman, with involvement of the left arm, chest, spine, and impressive soft tissue involvement. In the past, she had undergone multiple vascular interventions. She presented with spontaneous massive bilateral chylothorax. After conservative treatment without success, we conducted bilateral pleurodesis. This resulted in a clear reduction of pleural effusions, but her medical condition subsequently worsened due to progressive parenchymatous infiltrates, and increased interlobal pleural effusions. She ultimately died of global respiratory insufficiency. In patients with melorheostosis, involvement of the soft tissue can result in distinctive morbidity, and whenever possible, treatment should be conservative.

Scleroderma-like disorders.

Fibrosing disorders comprise a wide spectrum of heterogeneous diseases characterized by sclerosis of the dermis, subcutis, and sometimes the underlying soft tissues and bone. The hallmark of this group of diseases is skin thickening as in systemic sclerosis with a different distribution pattern and for this reason they have also been referred to as "scleroderma-like" disorders. These diseases may have a different clinical course ranging from a benign disease with a localized cutaneous involvement, to a widespread, systemic, life-threatening disease. Some of them are associated with autoantibodies and/or autoimmune conditions. An accurate recognition of these scleroderma-like diseases is important for the institution of the most appropriate treatment.

Soft tissue knee contracture of the knee due to melorheostosis, treated by total knee arthroplasty.

Melorheostosis is a rare condition which can cause soft tissue joint contractures. We present a case of melorheostosis causing disabling knee joint contracture, treated successfully by total knee arthroplasty.

Myelopathy associated with melorheostosis: a case report.

A man in his mid thirties presented with lower-extremity weakness and spasticity because of a myelopathy caused by a rare disorder of bone known as melorheostosis. The primary pathology involved was compression of the cord at the cervicothoracic levels by dystrophic osseous formation within the vertebral bodies. Based on a review of existing literature, it was evident that the spine is an uncommon location to find melorheostosis, making this disease entity a unique cause of myelopathy. The patient's progress was closely observed during his inpatient rehabilitation program, after he underwent spinal decompression surgery. Starting from the level of complete paralysis, he was able to regain functional strength in his legs by the end of his 2-month course. Despite the lack of reported outcomes in cases of myelopathy associated with melorheostosis, our report describes a favorable prognosis with good recovery of both strength and function.

Melorheostosis in a family with autosomal dominant osteopoikilosis: report of a third family.

We describe a three-generation family with clinical and radiological findings of osteopoikilosis in five and melorheostosis in one individual. The co-occurrence of both rare bone disorders suggests that both conditions might be related as suggested previously by Butkus et al. [1997: Am J Med Genet 72:43-46] and Nevin et al. [1999: Am J Med Genet 82:409-414]. The findings in this family strengthen the hypothesis that osteopoikilosis is an autosomal dominant condition and that an early postzygotic second hit mutation in the second allele results in melorheostosis.

Melorheostosis: a case report and literature review.

Melorheostosis is a rare form of cortical hyperostosis that resembles wax dripping down the side of a candle. This disease usually affects the long and short bones of an extremity. Literature review and a case report will be discussed with respect to incidence, clinical presentation, radiographic appearance, and treatment.

Melorheostosis and the sclerotomes: a radiological correlation.

Melorheostosis is characterised radiologically by hyperostotic linear densities in bone. These densities have a peculiarly segmental distribution which does not correspond with the anatomical course of blood vessels or mixed nerve roots of the limbs. So far this disbritubion has lacked any valid explanation, although it has been suggested to be a developmental error as a result of an embryonic metameric disturbance. Inman and Saunders in 1944 described a sensory nerve supply to skeletal structures with 'sclerotomes' representing the zones of the skeleton supplied by individual spinal sensory nerves. Radiographs of 30 cases from the Radiological Museum of the Institute of Orthopaedics, London, have been reviewed and an attempt has been made to correlate the sclerosing lesions with the sclerotomes. The investigation was handicapped by paucity of films and clinical information, but in 19 cases the skeletal abnormalities were considered to correspond with a single sclerotome or part thereof. These studies were convincing when films of an affected hand or foot were available. In the remaining 11 cases multiple sclerotomes appeared to be involved and the clinical manifestations were correspondingly more severe. It is proposed that melorheostosis may be the late result of a segmental sensory nerve lesion, to account for its sclerotomal distribution. The association with linear scleroderma is discussed, since it has been suggested that these cutaneous lesions are related to the same nerve segment. Eight cases showed paraarticular ossification of soft tissues which may be related to involvement of a corresponding myotome.