Juberg-Marsidi Syndrome: Causes, Symptoms & Treatment

Juberg-Marsidi syndrome is a hereditary disorder associated with mental retardation and physical disorders. The syndrome is rare, with one case per million births. It is caused by a mutation in the ATRX gene.

What is Juberg-Marsidi syndrome?

Juberg-Marsidi syndrome, also called Smith-Fineman-Myers syndrome or X-linked mental retardation-hypotonic facies syndrome I, is a hereditary disorder. It belongs to the group of “syndromes with an association of intellectual deficit and hypotonic face.” The disease was first described in 1980 by the American pediatricians Richard C. Jubert and I. Marsidi. Since then, several cases of the disease in unrelated families have been described. Overall, the disease is very rare, with one case per million births.

Causes

Juberg-Marsidi syndrome is inherited. It is an x-linked recessive inheritance. In x-linked recessive inheritance, the trait-bearing gene is located on the X chromosome. This means that the disease is inherited in a sex-linked manner. As a rule, women are only carriers of the disease. For a woman to have the disease, both the father and the mother would have to carry a diseased X chromosome. With only one diseased X chromosome, recessive inherited disease does not prevail. Thus, women are usually exclusively conductors. This means that they carry the diseased gene but do not exhibit any corresponding disease characteristics themselves. Since men, unlike women, have only one X chromosome, they are affected by the disease if the damaged X chromosome was transmitted from the mother. Roughly speaking, it can be said that if the father has the disease, all sons will be healthy and all daughters will be conductors. If the mother is a carrier of the damaged X chromosome, 50 percent of the sons will have the disease. 50 percent of the daughters would again be conductors. The cause of the syndrome is a mutation in the so-called ATRX gene in chromosomal region Xq25 approximately in an interval of 19.8Mb.

Symptoms, complaints, and signs

The main symptom of Juberg-Marsidi syndrome is severe intellectual disability. This is manifested by below-average cognitive abilities and, consequently, a marked limitation in emotion and disposition. The intelligence of the affected children is significantly reduced. The growth and developmental disorders already begin in the womb, so that the children are already born deaf or hard of hearing. The malformed faces of the affected children are striking. The facial features are rather coarse with a rather narrow face, the lips are very prominent. The lower lip appears drooping. The upper central incisors appear equally prominent. In general, the teeth are quite wide apart. The eyebrows are bushy, the eyelid axes are slanted, while the palpebral fissures are rather narrow. At the corners of the eyes there is a fold of skin lying in front of the eyelids. This skin fold is called epicanthus. The bridge of the nose is broad and flat with an extended nasal tip. This nasal deformity is also called a saddle nose. Overall, the head of affected children is smaller than the head of healthy children. The auricles of the affected children are also malformed. This is also referred to as auricular dysplasia. The growth disorders continue during development, so that the children remain short in stature. The muscles are weakly developed, and muscle spasticity may occur. Kamptodactyly is found on the hands. This is a bending contracture of the middle joints of the little finger and in rare cases also of the ring finger. This is probably caused by a shortening or shrinking of tendons and tendon sheaths. In addition to camptodactyly, clinodactyly may also occur in Juberg-Marsidi syndrome. In clinodactyly, a phalanx is bent laterally in the hand skeleton. Another symptom of Juberg-Marsidi syndrome is microgenitalism. The penis and scrotum are underdeveloped. This is also referred to as micropenis. There is also testicular dystopia, which is a positional abnormality of the testis. In this case, the testicle lies temporarily or permanently outside the scrotum.

Diagnosis and course of the disease

The symptoms of Juberg-Marsidi syndrome are quite striking, but because the condition is very rare, diagnosis is usually not made directly.Initial indications include deformities of the skull, low birth weight, genital malformations and hearing loss. In the course of the child’s development, physical developmental disorders and limitations in cognitive development are added. Certainty as to whether the condition is really Juberg-Marsidi syndrome can only be provided by genetic testing of the child and parents.

Complications

Juberg-Marsidi syndrome usually causes significant mental and physical disorders and discomfort in the patient. These can significantly limit the affected person’s life and daily routine. In most cases, patients are also dependent on care from family or caregivers. Already in childhood there are disturbances in growth and development. Furthermore, severe mental retardation also occurs. As a result, children in particular can become victims of bullying or teasing. Likewise, the patient’s facial features are altered and short stature occurs. The muscles are also only relatively weakly developed and the patient’s resilience is significantly reduced due to Juberg-Marsidi syndrome. It is not uncommon for a micropenis to develop as well. The head of the affected person is also significantly smaller than in healthy people. Furthermore, hearing loss and eye complaints occur. A causal treatment of Juberg-Marsidi syndrome is not possible. Therefore, only the symptoms of the syndrome can be limited, and various therapies are necessary. No particular complications occur. The life expectancy of the patient may be reduced by Juberg-Marsidi syndrome. Furthermore, the patient’s parents often require psychological treatment as well.

When should you see a doctor?

Parents should visit a doctor with their children as soon as the first physical or mental abnormalities of their offspring become apparent. If there are developmental delays, difficulties within various learning processes, or if decreased intelligence is perceived in direct comparison to children of the same age, a visit to the doctor should be made. In case of reduced hearing ability, deformities of the ears or an overall weak musculature, the initiation of control examinations is advisable. Physical abnormalities, adhesions or deformities should be presented to a physician as soon as possible. If children do not learn to walk or cannot use their limbs sufficiently, the cause must be determined. If there are shortened fingers, visual abnormalities in the shape of the hand or joints, or if the child is short stature, there is cause for concern. Early diagnosis is crucial for the effectiveness of possible therapies. Therefore, a doctor should be consulted already at the first irregularities. Boys suffering from Juberg-Marsidi syndrome also exhibit growth disorders of the sex. A micropenis or abnormalities of the testicles are among the criteria that indicate a disease and should be examined. If the children have the feeling of being overtaxed in everyday play activities, if they do not become independent despite all efforts, or if persistent comprehension problems are evident, a visit to the doctor is advisable.

Treatment and therapy

There is no specific therapy for Juberg-Marsidi syndrome. Treatment is purely symptomatic. Occupational therapy and physical therapy can help children develop. Hearing specialists and ophthalmologists are also usually part of the treating team because of the impairment of the sensory organs. Surgical intervention may be indicated to correct eye misalignment and vision problems. In most cases, the affected children also require hearing aids. The earliest possible therapeutic support is indispensable in the treatment of Juberg-Marsidi syndrome. Only in this way can the children be supported in time and possible developmental deficits can still be compensated in time.

Outlook and prognosis

Juberg-Marsidi syndrome has an unfavorable prognosis. This syndrome represents a mutation in the patient’s genetics. Legal requirements prohibit scientists and researchers from intervening and altering human genetics. As a result, a cure for the affected person is not possible. In their treatment, doctors concentrate on improving the patient’s well-being and quality of life. Unnecessary interventions, which can only produce an optical beautification, are avoided.The sooner a comprehensive treatment plan is created and various therapies are started, the better the chances of success for support and the reduction of developmental deficits. Since the disease is characterized by severe mental retardation, despite all efforts, it is not possible to achieve a state of health that allows a life without medical assistance and daily support. For life, the affected person needs medical care as well as all-day care. Various dysfunctions as well as physical changes occur in this disease and lead to severe impairment in coping with daily responsibilities. Surgical interventions are performed to achieve an improvement of natural functions. Each intervention is associated with risks and side effects. Complications and new disorders may occur. In many cases, the existing complaints trigger secondary diseases, which must be taken into account when making an overall prognosis.

Prevention

Juberg-Marsidi syndrome cannot be prevented. With the help of prenatal diagnostics, genetic defects can be detected early. Heterozygote diagnostics can determine whether either parent carries the defective gene and could pass it on to the child if it were to reproduce. In Germany, the genes of unborn children may only be tested for certain diseases in exceptional cases. In this case, the genetic material of the embryo can often already be differentiated exclusively from the genetic material of the mother. Ethically, however, prenatal genetic testing is quite controversial.

Follow-up

The measures of an aftercare are usually very limited in Juberg-Marsidi syndrome or are not available to the affected person at all. In this regard, the primary need for the patient to see a physician early in the course of this disease is to avoid further complications or other medical conditions that could possibly continue to reduce the quality of life. Therefore, the main focus in this disease is early detection and treatment of Juberg-Marsidi syndrome. Since this is a hereditary disease, it cannot be completely cured. However, if a child is desired, genetic testing and counseling should always be done to ensure that the syndrome does not reoccur in descendants. In most cases, the symptoms of Juberg-Marsidi syndrome are treated by the measures of physiotherapy or physical therapy. Many of the exercises from such therapy can be repeated in the patient’s own home, which can continue to relieve symptoms. In the case of visual disturbances, affected persons should wear visual aids so that these disturbances do not continue to worsen. Especially in the case of children, parents must pay attention to the correct use of visual aids. In the case of psychological upsets, intensive discussions with one’s own parents or with relatives and friends are very helpful.

What you can do yourself

Patients with Juberg-Marsidi syndrome are significantly impaired in their physical as well as mental development and often unable to lead an independent life. Thus, most opportunities for self-help are also unnecessary, since it is primarily the guardians who influence the patient’s condition. Although the quality of life is severely limited by the disease, the physical and mental condition of the patient often improves with care appropriate to the disability. With regard to mental retardation, those affected usually attend a special school facility. The educators there take into account the individual intellectual condition of the patient and support him accordingly in the best possible way. In the school and other care facilities, the affected person usually gets to know helpful social contacts that make it easier to deal with the rare disease and increase the perceived quality of life. Certain symptoms can be alleviated by suitable medications, with parents paying attention to the correct dosage. In general, patients usually visit various doctors several times a year, who monitor the various symptoms of the disease and prescribe further therapies. The physical disability prevents the practice of specific types of sports, yet some sporting alternatives remain. A physiotherapist helps the affected person to strengthen his motor skills, which facilitate everyday life.