Lujan -Fryns syndrome (or LFS according to Abbreviation Finder) is an X-linked inherited disease that leads to intellectual disability and marfanoid stature. So far, the disease is considered incurable.
What is Lujan-Fryns Syndrome?
Another name for the Lujan-Fryns syndrome is: X-linked mental retardation with Lujan syndrome with simultaneous marfanoid habitus. It was first observed in 1984 by the American pediatrician J. Enrique Lujan in four male patients. In 1987, the human geneticist Jean-Pierre Frans described two cases with the same symptoms. The very rare disease was named after these scientists.
Lujan-Fryns syndrome causes mild to moderate intellectual disability with simultaneous marfanoid stature, facial dysmorphism, and behavioral problems. It can also cause birth defects that affect the heart and brain. According to the ICD-10 diagnostic classification system, Lujan-Fryns syndrome is classified as mild intellectual disability with clear behavioral disturbances, observation is advised.
Mutations in the MED12 gene are responsible for Lujan-Fryns syndrome. MED12 is a subunit of a multiprotein complex that regulates transcription, a mediator. The cases examined showed a point mutation, more precisely a substitution. This is the case when one base of the DNA is exchanged for another. The category of substitution present in Lujan-Fryns syndrome is a missense mutation of type p.N1007S.
This means that the amino acid asparagine, which should normally be at position 1007 along the MED12 sequence, was mistakenly replaced with serine. The mutation causes incorrect expression of the protein being encoded, leading to the disorder. The affected gene can be located on the X chromosome, its gene locus is 13.1. However, the exact etiology is still unclear.
Symptoms, Ailments & Signs
Typical symptoms are mild to moderate intellectual disability, but individual cases of severe intellectual disability are also known. In addition to the mental limitations associated with marfanoid habitus, people affected by Lujan-Fryns syndrome usually have a facial physiognomy typical of the disease. Marfanoid habitus is a group of physical characteristics that are typical of Marfan syndrome.
These include a high forehead, a long face with narrow features, and a large nose with a high nasal bridge, often hypoplasia of the upper jaw, a short, deep philtrum, and a high palate. Long hyperextensible limbs, fingers and toes are also typical. The big toe is relatively short, the second toe too long.
A brain abnormality often associated with the syndrome is agenesis, i.e. the lack of formation and development, of the corpus callosum, also called cerebral beams. This tissue, consisting of around 250 million nerve fibers, connects the two hemispheres of the brain. One of the most common abnormalities in the behavior of sick people is a disorder similar to that of people on the autism spectrum.
Other mental disorders that may be associated with Lujan-Fryns Syndrome include psychotic behavior, schizophrenia, hyperactivity and attention deficit disorder, oppositional defiance, obsessive -compulsive disorder, low frustration tolerance, poor impulse control, learning disabilities, short-term memory deficits, and poor appetite to the point of malnutrition. In individual cases, the Lujan-Fryns syndrome also occurs without mental impairments.
Diagnosis & disease progression
Lujan-Fryns syndrome mainly affects men, which probably has a genetic cause. However, exact prevalence figures are not known. Until 2007, only a clinical diagnosis of the syndrome was possible, since the corresponding gene has been identified, the diagnosis can be made by DNA analysis. In a diagnosis based on the symptoms, the psychopathological behavioral patterns of the patient are taken into account in addition to physical findings.
Lujan-Fryns syndrome differs from other forms of X-linked mental retardation in the accompanying marfanoid habitus. However, the marfanoid habitus can often only be recognized during puberty, since the physical structures of the patients have not yet developed accordingly. For the DNA diagnosis, the patient’s blood and that of other family members are examined. Exon 22 of the MED12 gene, including the intron/exon splice sites and the flanking intronic regions, is analyzed using sequencing.
In the differential diagnosis, there is another condition that shares some similarities with Lujan-Fryns Syndrome and is also due to a mutation in the MED12 gene, Opitz-Kaveggia Syndrome. DNA analysis shows that it is a missend mutation p.R961W.
First and foremost, Lujan-Fryns syndrome leads to a sharp reduction in the patient’s intelligence. As a result, those affected are often dependent on the help of other people throughout their lives and are unable to cope with everyday life on their own. For this reason, the relatives and parents of the children are also severely affected by Lujan-Fryns syndrome and often suffer from psychological limitations or depression.
Those affected are hyperactive and often schizophrenic. Obsessive-compulsive disorders or defiant behavior occur, which can have a very negative effect on the social environment. Especially at a young age, Lujan-Fryns syndrome can lead to bullying or teasing in the patient. Furthermore, the syndrome can also lead to malnutrition or loss of appetite and thus significantly reduce the quality of life.
Various learning disabilities can also occur. In some cases, this syndrome causes heart problems or epileptic seizures. The treatment is therefore only carried out symptomatically and aims to reduce the symptoms. However, complete healing is not possible, so that the patients are usually dependent on long-term care. However, the life expectancy of those affected is not reduced by the syndrome.
When should you go to the doctor?
If children and adolescents show clear delays in their development process in direct comparison to their peers, the observations should be presented to a doctor. If there is a learning disability, memory problems, interruptions in memory, or if a mental abnormality is perceived, a doctor should be consulted. Optical abnormalities on the child’s face are another sign of an existing irregularity. A particularly high forehead, a long, narrow face or a changed nose shape should be checked out by a doctor.
If the fingers or toes can easily be hyperextended, this is unusual. Although there is no pain, the ability to move indicates a disease that needs to be examined by a doctor. Disorders of attention, compulsions, a reduction in the ability to speak or behavioral problems must be examined by a doctor. If the person concerned shows an aggressive demeanor, has a low frustration limit or cannot control impulse actions, a doctor’s visit is necessary.
If the behavior of people from the social environment is considered to be above the norm, a doctor’s assessment should be obtained. The person affected often needs medical help to prevent self-destructive actions. A decrease in body weight, loss of appetite or a change in posture should be discussed with a doctor. Hyperactivity, psychopathic behavior or hallucinations should be evaluated by a doctor as soon as possible.
Treatment & Therapy
Due to the genetic origins of the syndrome, there is currently no specific causal treatment for patients suffering from Lujan-Fryns syndrome. The disease is considered incurable. Nevertheless, there are corrective procedures, preventive interventions and various therapies for dealing with the craniofacial, orthopedic and psychiatric problems of the patients.
Irregularities with the heart and possible epilepsy should be checked regularly and, if necessary, treated with medication. Orthopedic deformities can sometimes be improved with physiotherapy. Psychological care for sick people is also useful.
The treatment focuses on promoting mental development on the one hand and early detection of any psychoses and schizophrenia that may occur on the other. Impulse control, avoidance of angry outbursts and socially incompatible behavior can be learned with special education and psychological care. The disease is inherited dominantly via the X chromosome. This means that a defective gene inherited from an affected parent is sufficient for the disease to be passed on.
Outlook & Forecast
Lujan-Fryns syndrome has an unfavorable prognosis. The cause of the syndrome is based on a genetic defect. Since human genetics cannot be modified due to the current legal situation, there is no way to remedy the cause of the symptoms. Physicians and scientists are therefore concentrating on the development and application of therapies for symptomatic treatment.
The disease is associated with severe intellectual disability. For this reason, those affected cannot cope with their entire life without the help of other people. You are unable to lead an independent life. They are completely dependent on the support of nursing staff or the support of loved ones.
The disease poses a particular challenge in overcoming the symptoms. The risk of an additional mental illness is therefore particularly high among the patient’s relatives. In medical care, the disturbance of cardiac activity should be minimized. Lifelong drug treatment must be initiated to avoid risks and complications.
Special educational and psychological therapies are used to improve the quality of life. Early intervention programs also support the course of the disease and show improved cognitive performance. However, the disease remains incurable. Likewise, the state of an independent lifestyle is not achieved despite all efforts.
Since Lujan-Fryns syndrome is a genetic disease, there is no way for the individual affected to protect themselves from the disease. Since there is no risk of contamination for the environment for the same reason, no prophylaxis is necessary.
When you have an intellectual disability, care and follow-up can make a big difference. The aftercare measures can include both psychosocial and physiotherapeutic measures. Depending on the age of the mentally handicapped person, a more comprehensive participation in the life of others can be gained with language and speech promotion or the promotion of motor skills.
In addition, genetic causes can also include physical limitations such as short stature or club feet. These also require medical or orthopedic follow-up treatment and monitoring. Aftercare for people with mental disabilities includes comprehensive measures that vary depending on the family situation and the degree of disability.
Mentally handicapped people can have a beneficial everyday life in a special workplace. You need assisted living services. Given the opportunities available today, many people with an intellectual disability can lead an independent life without much difficulty.
You can do that yourself
Those affected with Lujan-Fryns syndrome have no special options for self-help. As a rule, the symptoms of this syndrome cannot be treated directly, so that a cure cannot occur.
Only a certain reduction in symptoms through intensive care and therapy can occur. The reduced intelligence can be treated with various exercises. The parents and relatives of the patient are particularly in demand here, as they have to support and encourage the person concerned. This can prevent further complications in adulthood. The occurrence of mental illnesses should also be diagnosed at an early stage in order to avoid mental disorders. Above all, outbursts of anger or psychoses must be taken into account. Conversations with friends and family also have a positive effect on the disease.
The heart problems can only be alleviated by surgical interventions, whereby regular examinations are highly advisable. Contact with other affected persons and their parents can often prove to be very useful, since this can lead to an exchange of information, which can make everyday life easier.