Multicentric Carpo-Tarsal Osteolysis Syndrome (MCTO) and “Function Profile”: a rehabilitative approach

In the last years, genetic advances led to a better knowledge of the biological basis of rare bone diseases and a new therapeutic perspective. Besides available or future drug therapies, physical medicine and rehabilitation are important therapeutic options. Indications of rehabilitation are available only for less rare skeletal diseases like achondroplasia or osteogenesis imperfect [1], but for other rare genetic bone diseases rehabilitation plan is neglected, not specific and reported only for a single patient.

Starting from the experience in an ultrarare disease, Multicentric Carpo-Tarsal Osteolysis Syndrome (MCTO), we propose a way to identify a rehabilitation plan based on specific disease (biological disease mechanism and natural history of the disease) and patient individual needs, aware that often the endpoint is not the recovery of full function but improvement or maintenance of starting point. The statement “specific” rehabilitation is about the patient’s rehabilitation plan, not the disease. The progression of the disability cannot be predicted due to the clinical heterogeneity of MCTO, similar to other genetic disorders.

Therefore, the rehabilitation plan must be specific to the patient, patient-centered, and modified as the disease progresses.

The rehabilitation plan aims to achieve and maintain as much autonomy as possible in meaningful life contexts for patients. The rehabilitation aims are to achieve and maintain as much autonomy as possible in meaningful life contexts for patients with the highest possible quality of life and improve participation in the activity of daily living.

MCTO with or without nephropathy is an autosomal dominant disease due to V-maf musculoaponeurotic fibrosarcoma oncogene ortholog B (MAFB) encoding the basic leucine zipper transcription factor MafB, which regulates the receptor activator of nuclear factor-kB ligand (RANKL); the consequence of genetic defect is an increase of bone reabsorption. Usually, osteolysis starts in pediatric age from carpal and tarsal bones with further reabsorption of other hand and feet bones as well as limb bones; severely affected patients develop deformity of interphalangeal, metatarsophalangeal, metacarpophalangeal, wrists elbows and knees joints [2]. Older patients develop defects of mineralization.

The disease is heterogeneous in age of appearance and progression of the same. The secondary and tertiary injuries that can worsen it are varied and can result in progressive disability and severe functional limitations. The disease’s onset in early childhood and being a “moving target” during personal growth and development may make this even more complicated.

Therefore, for every patient is essential an accurate, complete and repeated clinical-functional assessment over time and a multidisciplinary approach to care is essential. In our experience, patients effectively present pain during the process of osteolysis at the onset of the disease [3, 4]. Patients do not complain of pain, but they do have functional limitations once the flare-up phase is over. Clinical assessment to identify a rehabilitation plan cannot be performed during active osteolysis, when there is pain, but only after flare-up episodes to monitor the possible and often unpredictable evolution of this rare disease and to modulate the necessary rehabilitation intervention [5, 6].

We describe a case series of MCTO patients diagnosed and followed by one centre, with the purpose of focusing on tools to capture functional impairment as a possible clinical marker of disease progression in view of future etiological therapies; furthermore, we delineate an approach to symptomatic therapies and specific clinical management including rehabilitation approach (physiotherapy, hydrotherapy and occupational therapy patient-centred).

Functional assessments are carried out by the physiatrist and occupational therapist, independently, in order to establish the patients’ functional abilities and the correlation between residual motor skills and their level of autonomy and participation.

Among the various possible evaluations, we chose the ones that we felt best enabled us to monitor disability, which was closely linked to the extremely heterogeneous clinical expression of this disease, according to the age of the patients at the time of observation. We thus followed 9 patients between 2 and 46 years old, all characterized by a genetic variant of MAFB. In this paper, we collected all patients from whom we obtained all the necessary data for a complete functional evaluation.

With no specific scale for the assessment and follow-up of this rare disease, we used other assessments to determine the level of impairment and restriction of children’s activity in everyday life. We concentrated on the evaluations of the International Classification of Functioning, Disability and Health: Children and Youth (ICF-CY), including the area of Body function and Structure, as well as the field of Activities and Participation [7].

In our case studies, nobody had pain at the time of assessment, once the flare-up phase was over and all patients had aROM-pROM impairment in one or more joints; the wrist was modified in the 6 patients (4 bilateral and 2 unilateral) and there was an ulnar and a radial deviation; 5 patients had a single or bilateral elbow involvement; 3 patients had knee, ankle and foot damage (Table 3) (Figs. 1, 2, 3, 4).

Muscle strength, measured using the Manual Muscle Test (MMT), decreased significantly by 4/6 patients in the muscles of the most affected joints in the forearm, wrist, hand and knee. The greater the number of joints, the weaker the strength (Table 4).

In the patient group, the CHAQ average was 0.956 (range 0–3); mRS 2.33 (range 0–6): 2 patients had level 4 (moderate-severe inability to walk unaided and inability to take care of one’s own bodily needs without assistance) and all other patients had levels 0–3; and PAI 17.5 (range 1–100), significantly reduced for all patients. The COPM interview was administered to 6 patients. Each patient exhibited a different limitation and priorities in their independence, but, apart from their functional limitation, they showed a relevant agreement in the specific activity of daily life. 5 of them mentioned personal performance problems connected with self-dressing, particularly the management of shirt or pants buttons; 4 of these had problems during the meal such as using a knife to cut meat or peeling an apple or cork from a bottle. 2 patients reported problems with personal hygiene. Only one indicated difficulties and issues related to recreation. Of the 6 patients assessed, one was equipped with an electronic wheelchair, one used a manual wheelchair with an electrical drive and walker, and one used a manual wheelchair only sporadically for long distances. During the interview, it appeared that 5 of them had used or used wrist-hand orthosis. Of these 5, only one kept on using it while the others have gradually abandoned the use. All components used in ICF (Body Functions and Structures, Activities and Participation) are quantified using a generic scale (0–4) (Table 5).

So our data confirm the heterogeneity of the clinical manifestations of the musculoskeletal system of MCTO with important functional limitations and various levels of disability. All patients are affected by at least one body joint. The number of joints involved corresponds to a higher disability and severity evaluation level (CHAQ/mRS). The involvement of the bilateral knee, ankle and foot with a significant deficiency in active and passive ROM is associated with a significant limitation or loss of gait. 4 out of 6 patients can walk autonomously at the right time, while 2 completely lost gait. The only child who reached late walking independence developed the disease around 12 months. The 2 patients who lost their walk were the ones whose lower limb joints were most affected. Hence it can be suggested that greater joint lesions at the lower extremities are correlated with a greater risk of loss of gait. Our patient group has a CHAQ average of 0.956 (range 0–3), mRS 2.33 (0–6) and PAI 17.5 (1–100). Overall, therefore, limitations in daily activities and the resulting impairment are mild to moderate. Physical activity is considerably reduced from what might be expected when correlated with CHAQ and mRS scores.

To define some kind of reliable, reproducible and comparable “function profile” within the same group for each patient, we have tried to measure a variety of global disease outcomes based on the International Classification of Functioning, Disability and Health: Children and Youth (ICF-CY) domains. This profile could be used to define the burden of the disease, its impact on the complexity of the individual and the burden on caregivers. By including more findings in the domains of the ICF model, we would like to have a better functional appearance in MCTO and possibly also in other ultrarare diseases. Perhaps this model could also be used to evaluate the effectiveness of proposed rehabilitation programs, for example, by learning from the outcomes in a domain such as body structure and function, translating into another, such as activity and participation.

Throughout their history of the disease, our patients have all received rehabilitative treatments and in the majority of cases the wrist-hand positioning orthosis was worn. Appraisals show considerable heterogeneity towards rehabilitation. This is due to the presence of a different phenotypical expression of the disease and the difficulty of arriving at a definitive diagnosis. The difference in time between onset and diagnosis does not facilitate the implementation of well-managed rehabilitation [24].

In all cases, every patient at the time of diagnosis requires a functional evaluation that should be repeated over time to adjust the course of rehabilitation. When symptoms of the disease occur at an early stage (less than a year of life), it is crucial to reach the development of motor stages. It supports and assures the acquisition of anti-gravity skills and the achievement of an independent walk.

Evaluations highlight the importance of early rehabilitation management, which may be critical to increasing the independence and participation of the patient with MCTO, limiting the secondary and tertiary damage of the pathology, deconditioning the retractions of the muscle tendons and the loss of movement until immobility. Despite the small numbers, our data may not be significant, but it allows us to focus more on the type and indication of rehabilitation treatment.

Physiotherapy can prevent muscular retraction and atrophy, which can worsen the genetic alteration of ROM and withdrawal. Hydrotherapy can be a complement to many treatment programs to reduce muscular rigidity and allow vertical and active walking assistance, even in severely compromised patients. Both are essential to reach the development of motor milestones when the illness begins in early childhood. Occupational therapy is recommended to determine accommodation measures to support participation in activities relevant to the patient, adjustment of daily living environments and the identification of equipment to support mobility and postural management.

Most of our patients had a postural orthosis during the course of their disease to prevent malformations, especially of the wrist and hand. Ulnar deviation is present in all patients, and significant articular limitations have been established in any case. The use of orthosis does not seem to indicate the effectiveness of preventing malformations [25]. The function of the wrist and hand in these patients is more important than using night splints to ensure wrist and hand alignment such as in juvenile idiopathic arthritis. In the future, in the event of new therapeutic prospects, it may be useful to re-evaluate the description made at this point in their rehabilitation journey.

We believe it is important to use a comprehensive and longitudinal “function profile” for health and disability. To this end, the ICF-CY approach establishes a common language for describing health and related conditions, enabling the comparison of data collected and a systematic coding scheme. ICF has a comprehensive approach that can be used as a model for other patients with rare diseases or with very specific characteristics (where each case is unique).

MCTO is complex and heterogeneous in its manifestations, although it is simply the involvement of the musculoskeletal apparatus. Lytic lesions, bone loss, generalized osteopenia, posture changes and secondary soft tissue involvement identify functional limitations, loss of independence, and disability with different images that can also be progressive, need to be monitored regularly in time and involve different approaches to rehabilitation. Physiotherapy and occupational therapy are important for the treatment of MCTO symptoms. They are helpful in preventing, reducing or alleviating functional limitations and the resulting disability, trying to maintain the best quality of life for these patients.

We believe it is important to have a complete, periodic and longitudinal functional evaluation of our patients, at the time of diagnosis, after every flare-up and once a year, not only for rehab plans, but also for prescribing devices.

This allows us to monitor the possible local or generalized consequences of MCTO and its impact on autonomy. In our case studies, the functional clinical type, so heterogeneous and so different from one another, but potentially progressive from a disability perspective, implies different approaches to rehabilitation.