Fukuyama type muscular dystrophy is a rare, congenital muscle wasting disease that occurs mainly in Japan. The disease is caused by the mutated so-called FCMD gene, which is responsible for coding the protein fukutin. The disease is associated with severe mental and motor developmental abnormalities and shows progressive course, resulting in a mean life expectancy of only about ten years.
What is muscular dystrophy type Fukuyama?
Fukuyama type muscular dystrophy (FCMD) is one of the genetic congenital muscle wasting diseases whose symptoms are evident at birth. The rare FCMD is inherited in an autosomal recessive manner. Its main area of distribution is Japan. The disease is associated with severe mental and motor developmental disorders and is causally related to a miscoded transmembrane protein called fukutin. Fukutin is synthesized in greater amounts in the central nervous system, pancreas, heart, and skeletal muscle. Because of the central and systemic importance of the protein fukutin in cell metabolism, primarily in the Golgi membrane of cells, severe systemic symptoms occur. Usually, during the first five years, the disease is accompanied by a severely elevated CK (creatinine kinase) level, which can reach ten to fifty times the normal concentration.
Causes
The direct cause of FCMD is a functional impairment or a complete loss of function of the structural protein fucutin. This is a so-called single-pass transmembrane protein that performs central functions in the membrane of Golgi organelles. The complex tasks of the Golgi apparatus of a cell include the formation and storage of secretory vesicles and intracellular lysosomes. The functional restriction of fukutin is due to a gene defect that leads to a miscoding of fukutin. This is one of several known mutations of the fukutin gene at gene locus 9q31-q33. The process that leads to the incorrect coding of fukutin because of the detectable gene mutation is not (yet) fully understood.
Symptoms, complaints, and signs
The first externally recognizable symptoms of congenic muscular dystrophy type Fukuyama usually appear in infancy immediately after birth. Typically, babies have only weak muscle tone, which manifests as general muscle weakness. Sucking and crying reflexes of the affected newborns are only weakly developed and a general flaccidity of the babies can be observed. Contractures, restricted movement of the hips, knees and interphalangeal joints are common and typical. In further development, typical myopathic facial features develop, which can be recognized by weak and “flabby” facial expressions. In many cases, the retina is also affected in the form of retinal dysplasia of varying severity and corresponding visual impairment. Equally symptomatic in later stages are so-called pseudohypertrophies of the calves and forearms, which result from an increase in interstitial connective tissue. Particularly serious, however, are symptoms of extremely slowed mental development, which is due to a maldevelopment in the attachment of important structures of the central nervous system (lissencephaly).
Diagnosis and course of the disease
Symptoms occurring immediately after birth that raise suspicion of FCMD should be clarified by electromyography or muscle biopsy and neurologic testing. Above all, other diseases such as Duchenne muscular dystrophy and Becker muscular dystrophy as well as muscular dystrophies associated with lissencephaly like FCMD must be excluded by differential diagnosis. Ultimate certainty can be obtained by molecular genetic testing of the fukutin gene. If cases of FCMD are already known within the family of one of the parents, molecular genetic testing can also be performed prenatally – without appreciation of possible ethical considerations. The course of the disease varies, but is always severe. The early recognizable mental and motor developmental disorders are so severe that only a few affected children learn to speak and walk. Epileptic seizures occur in more than half of the patients.In the further course – at the latest from the tenth year of life – swallowing and eating disorders as well as heart problems set in, which are ultimately associated with a very poor prognosis.
Complications
As a rule, muscular dystrophy type Fukuyama causes various limitations and complaints immediately after birth. Most affected individuals suffer primarily from severe muscle weakness. Ordinary activities are no longer possible for the affected person, which leads to significant delays and restrictions in development, especially in children. Furthermore, there are also mental and motor complaints. Those affected appear clumsy and not infrequently suffer from restricted movement. Likewise, unusual facial features occur, and children in particular may suffer from this complaint as a result of bullying or teasing. It is not uncommon for Fukuyama type muscular dystrophy to also lead to impaired vision or veil vision. The quality of life of the affected person is significantly reduced by this disease. Due to the disturbed mental development, the affected persons are not infrequently also dependent on the help of other people in their daily lives. A causal treatment of muscular dystrophy type Fukuyama is not possible, so that usually only the complaints and symptoms are treated. Complications do not occur. Furthermore, in acute emergencies, surgical interventions are also necessary to prevent cardiac arrest due to respiratory problems.
When should you go to the doctor?
Fukuyama type muscular dystrophy is usually diagnosed immediately after birth. The attending physician can determine the condition by muscle weakness and other typical symptoms and will promptly arrange for a detailed diagnosis. Parents of affected children must consult closely with the physician so that medication and physical therapy can be regularly adjusted to the rapidly changing symptom picture. Depending on the symptom picture, other specialists may need to be consulted, for example for the visual impairment that typically occurs. If epileptic seizures, swallowing and eating disorders or heart problems occur in the course of the disease, the nearest hospital must be visited immediately. In most cases, various complaints occur immediately after birth that make inpatient hospitalization necessary. In the case of a mildly pronounced muscular dystrophy of the Fukuyama type, outpatient treatment may be possible under certain circumstances. In addition to the family doctor, internists, neurologists, orthopedists and cardiologists can be consulted for this purpose. In the further course, the responsible physician will also involve a physiotherapist in the therapy.
Treatment and therapy
Therapy aimed at curing FCMD does not exist because there is no way to replace the transmembrane protein fukutin, which is incorrectly encoded for genetic reasons, with properly encoded fukutin. Applied treatments and therapies serve to delay the course of the disease as much as possible and to have a positive influence on the children’s quality of life. Physiotherapeutic exercises help to compensate a little for motor deficits and to slow down the progression towards joint contracture, i.e. towards joint stiffness and the process of muscle atrophy. In the case of acute orthopedic or other problems, individual intervention – including surgical intervention if necessary – is provided. In many cases, additional anticonvulsive treatments are necessary to prevent epileptic or other convulsive seizures. Gastroesophageal reflux is common, requiring surgical intervention beyond drug treatment. Special attention is paid to monitoring respiratory and cardiac function. Particularly in the advanced stages of the disease, problems increase and are a leading cause of death and thus require high attention. Ultimately, the treatments and therapies help improve the quality of life. Immediate life-prolonging interventions are acute interventions to overcome acute respiratory distress or to overcome acute cardiac problems with impending cardiac arrest.
Outlook and prognosis
The outlook for Fukuyama-type muscular dystrophy is poor. However, Europeans rarely have to fear disease. The main area of distribution is in Japan. There, one to two out of 50,000 children are born with Fukuyama type muscular dystrophy. The cause of the symptoms lies in a genetic defect. According to current scientific knowledge, this defect cannot be treated.Life expectancy is greatly reduced. Most of those affected do not live more than ten years. Depending on the severity of the symptoms, significantly earlier deaths are also possible in some cases. In addition, the quality of life also suffers. Many approaches are now available to curb the symptoms. These include, above all, physiotherapy, medication and breathing aids. However, the progressive development of Fukuyama-type muscular dystrophy cannot be slowed down overall. Children with the disease require close-meshed care. Difficulties in walking and standing are common. The number and intensity of limitations increase significantly after the age of five. For parents and relatives, the diagnosis of “muscular dystrophy type Fukuyama” often means a psychological burden. As a result, the treatment usually involves their problem situation.
Prevention
Direct preventive measures that could prevent the occurrence of congenic muscular dystrophy type Fukuyama do not exist, because the disease is based exclusively on a genetic defect and the incorrectly coded protein fukutin – the actual trigger of FCMD – cannot be replaced by correctly coded fukutin. For people of either sex in whose families cases of FCMD have already been documented, molecular genetic testing of the fukutin gene is recommended to obtain certainty about whether a corresponding genetic defect is present.
Follow-up
In Fukuyama-type muscular dystrophy, follow-up is very limited. For the most part, children receive follow-up care on an outpatient basis, but in some cases inpatient follow-up is necessary. Regular check-ups are important after diagnosis to monitor the development of the disease. Intensive care of the child is indispensable here. Since muscular dystrophy type Fukuyama cannot be treated, only the complaints and symptoms can be alleviated in the aftercare. This serves to increase the child’s quality of life despite the disease. Physiotherapy is one way to compensate for muscle weakness and the resulting motor deficits and to slow down joint stiffness. In some cases, additional orthopedic surgical procedures may also be necessary. Furthermore, breathing aids and various medications are advised to curb the sometimes severe symptoms. Here it is fundamental to check that these medications are taken regularly. Anticonvulsive treatments that help prevent epileptic seizures are also important in follow-up care. Continuous monitoring of the child’s respiratory and cardiac function is also necessary. Fukuyama type muscular dystrophy is a disease with no cure, and life expectancy is usually no more than ten years.
This is what you can do yourself
This very serious disease occurs mainly in Japan. Those affected usually die in infancy. These children depend on the help and protection of their parents, as they need constant care. Parents must ensure that their affected child reliably takes his or her medication and accompany him or her to physiotherapy sessions. Deteriorations in the course of the disease must be recognized and presented to the doctors for supplementary treatment. If the parents are overwhelmed by this, they should undergo supportive psychotherapy. In addition, joining a self-help group is recommended. The German Society for Muscular Dystrophy (Deutsche Gesellschaft für Muskelkranke e.V.) runs self-help groups throughout Germany that provide local advice and support (www.dgm.org). Joining a self-help group can also bring relief to the child itself. It is possible that the child will get to know other children affected by muscular atrophy and will be able to exchange ideas. This is all the more important if the sick child is bullied by other children in his or her immediate environment. If the parents or relatives of a child suffering from Fukuyama muscular dystrophy wish to have another child, they should seek genetic advice. A molecular genetic examination can show whether and in whom the fukutin gene that causes the disease is damaged.
