L1CAM syndrome is a rare inherited disorder. The mode of inheritance of L1CAM syndrome is x-linked. The typical symptoms of L1CAM syndrome are expressed as spasticity, adducted thumb, and various brain abnormalities in affected patients.
What is L1CAM syndrome?
L1CAM syndrome is also known by the synonymous names CRASH syndrome, MASA syndrome, and Gareis-Mason syndrome. These are each different manifestations of the L1CAM syndrome, which are associated with different symptoms of the hereditary disease. In principle, carriers of the genetic defect pass on the L1CAM syndrome to their offspring in an x-linked manner. The severity of the symptoms varies from case to case. Thus, mild courses as well as severe complications are possible due to the L1CAM syndrome. In principle, L1CAM syndrome is a developmental disorder of the affected patients that exists from birth. Typical for the L1CAM syndrome is a hydrocephalus with varying severity in individual cases. In addition, patients suffering from L1CAM syndrome suffer from mental retardation, adducted thumbs and spasms in the lower extremities. L1CAM syndrome can be divided into several subtypes that differ in terms of their leading complaints. The most relevant of these are MASA syndrome and corpus callosum agenesis. The L1CAM syndrome dominates in males. HSAS syndrome presents with an estimated frequency of approximately 1:30,000, making it the most common expression of congenital hydrocephalus. The prevalences of the other subtypes of L1CAM syndrome have not been studied.
Causes
The causes of L1CAM syndrome are found in genetic defects. Thus, specific genetic mutations are present in individuals affected with L1CAM syndrome that lead to the development of the typical symptom. The gene mutations occur on the so-called L1CAM gene, from which the name of the disease is derived. The mutations are located at the gene locus Xq28. The L1CAM gene is responsible for coding certain molecules for cell adhesion, which play a crucial role in developmental processes on the nervous system. Currently, more than 240 different gene mutations are known, resulting in the diverse symptoms of L1CAM syndrome. In addition, studies show that L1CAM syndrome results from new mutations in approximately seven percent of cases.
Symptoms, complaints, and signs
L1CAM syndrome occurs more frequently in men. Patients suffer from hydrocephalus, which varies in severity from individual to individual. Mental retardation also varies in severity. Spasms in the lower limbs and generalized hypotonia develop at a young age. The symptoms usually worsen with increasing age, so that atrophy develops in the muscles of the legs. Adducted thumbs are also typical of L1CAM syndrome and are seen in approximately half of all patients. Sometimes, individuals with L1CAM syndrome also suffer from epileptic seizures. Rarely, L1CAM syndrome is associated with Hirschsprung disease. In female patients, L1CAM syndrome usually manifests in milder symptoms.
Diagnosis and disease course
The diagnosis of L1CAM syndrome must be made in a specialized center. First, a history is taken with the patient and his or her parents, focusing on the individual’s symptoms and family history. After the patient interview, the physician uses numerous examination techniques, especially imaging methods. In male sufferers of L1CAM syndrome, the diagnosis is also based on neuropathological examinations. An MRI examination is also used as a standard procedure. A reliable diagnosis of L1CAM syndrome is possible by means of genetic tests that detect mutations of the L1CAM gene. The differential diagnosis is of particular relevance. In doing so, the physician distinguishes L1CAM syndrome from, for example, spastic paraplegia as well as other impairments of hydrocephalus. Prenatal diagnosis is possible and useful in female embryos if the corresponding gene is present in the family. Ultrasonographic examinations are also used.
Complications
In most cases, L1CAM syndrome leads to very severe mental retardation in the patient.As a rule, those affected are then always dependent on the help of other people in their everyday lives and can no longer perform many everyday tasks on their own. The development of the child is also considerably slowed down and restricted by the L1CAM syndrome, so that there are also considerable consequential damages and complications in adulthood. In the further course, muscle weakness and epileptic seizures occur. The affected persons suffer from severe pain and may even die from the seizures in the worst case. Furthermore, the affected person can also become a victim of bullying or teasing at school. The affected person’s communication and ability to concentrate are also impaired. Unfortunately, a causal treatment of L1CAM syndrome is not possible. Affected individuals are therefore dependent on various therapies to reduce the discomfort of everyday life. However, a complete cure does not occur. Furthermore, in the worst case, the patient may be stillborn. The life expectancy of the affected person may likewise be reduced by L1CAM syndrome.
When should you see a doctor?
Parents who notice spasms or low blood pressure in their child should inform the pediatrician. If L1CAM syndrome is treated early, the progression of the disease can at least be slowed. If no therapy is given, the symptoms worsen until muscle weakness and epileptic seizures eventually occur. Specialist advice is needed at the latest when signs of these symptoms are noticed. A diagnosed L1CAM syndrome must be treated permanently. Affected children must therefore see a doctor regularly and, depending on the symptoms, various specialists. If seizures, epileptic seizures or falls occur during therapy, parents must call the emergency medical services. The child must then be cared for in the clinic, as the seizures can recur within a short period of time. In addition, any injuries and the causes of the complications must be examined and treated. L1CAM syndrome is treated by a pediatrician as well as orthopedists, neurologists, internists, and physical therapists. If there are any psychological complaints, the medical professional in charge will also consult a psychotherapist.
Treatment and therapy
Currently, causal therapy for L1CAM syndrome is not possible because the disease results from genetic mutations and medicine currently has no control over such disorders. However, the symptoms of L1CAM syndrome are relatively treatable symptomatically, depending on the individual case. First, families with cases of L1CAM syndrome should seek genetic counseling. L1CAM syndrome itself is treated by various specialists, such as neurosurgeons, pediatricians, and orthopedists. The intracranial pressure can be reduced by means of a cerebrospinal fluid shunt. Adducted thumbs usually do not require therapy. Patients with L1CAM syndrome undergo regular medical checkups with various specialists to monitor physical and mental development and prevent complications. The prognosis of L1CAM syndrome is highly dependent on the individual severity of the symptoms. For example, hydrocephalus may result in stillbirth or death of the child at a young age. Less severe symptoms usually result in a much more favorable prognosis for patients with L1CAM syndrome. In addition, the quality of treatment also affects the course of L1CAM syndrome.
Outlook and prognosis
The prognosis in patients diagnosed with L1CAM syndrome is unfavorable. The disease is characterized by irreparable damage that cannot be sufficiently modified despite all efforts. The syndrome is based on a genetic defect. Since, for legal reasons, scientists are not allowed to alter human genetics, physicians have few options for treating the symptoms. Although the intensity of the individual symptoms varies from patient to patient, they are irreversible and severely disruptive to lifestyle. Affected people have a shortened lifespan. Damage to the brain occurs, resulting in immense cognitive losses and various functional disorders. Coping with everyday life is not possible without therapeutic help as well as everyday support.Various therapies are used to improve the quality of life of the affected person. The disease is a great challenge for the person affected and his or her relatives. Due to the emotional stress, secondary disorders are to be expected. The L1CAM syndrome has a progressive course. In the course of life, further complaints and unpleasant health developments occur. The muscular system is weakened and epileptic seizures occur. In addition, spasticity is part of the clinical picture of the health disorder. Although medication is administered to relieve the symptoms, recovery does not occur.
Prevention
Causal prevention of L1CAM syndrome is not yet practical. L1CAM syndrome is congenital and occurs as a result of genetic mutations. However, genetic counseling of families in which cases of L1CAM syndrome have occurred or corresponding genetic defects are known is possible. Ideally, counseling is done during family planning so that the risk of disease for children is reduced.
Follow-up
In L1CAM syndrome, very few, and sometimes no, aftercare measures are available to the affected person in most cases. In this disease, a physician should be consulted relatively early to prevent further worsening of symptoms or other complications. As a rule, self-healing cannot occur, so that the person affected by L1CAM syndrome is in any case dependent on medical examination and treatment. If the patient wishes to have a child, he or she should first undergo genetic testing and counseling to prevent the recurrence of L1CAM syndrome. Most affected individuals rely on various surgical procedures to alleviate the symptoms of this disease. After such interventions, the affected person should definitely rest and take care of his or her body. Strenuous and physical activities should be avoided, and stress should also be prevented in general. Many affected persons are also dependent on psychological care. Contact with other L1CAM syndrome sufferers can also be useful here. This not infrequently results in an exchange of information, which can make the patient’s daily life easier.
What you can do yourself
As a rule, L1CAM syndrome cannot be treated by self-help options, so patients are always dependent on medical treatment. However, even this can only be symptomatic and not causal. If L1CAM syndrome results in stillbirth or very rapid death of the child at a young age, the affected parents need extensive psychological support. Talks with close friends and relatives are helpful, and contact with other parents affected by L1CAM syndrome can also be helpful and lead to an exchange of information. Since the patients themselves are extremely limited in their everyday life, they are always dependent on loving care by people. Here, especially the care by the own family and friends has a very positive effect on the course of the disease. Mental retardation can also be counteracted. This can possibly be alleviated by various learning exercises, which can also be carried out at home. Should an epileptic seizure occur as a result of L1CAM syndrome, however, it must always be examined and treated by a doctor. In general, affected individuals rely on regular checkups with physicians to avoid further complications.
