What is Fragile X Syndrome?

Fragile X syndrome is an X-linked incompletely dominant genetic disease. It is named because the end of the X chromosome in a cell can show a fragile site like a break after the action of a mutagen in a special medium. Male patients show mental retardation, giant testis, special face, speech behavior disorder, etc. Male patients are more common and their symptoms are more severe. About 1/3 of female carriers show mental retardation or other symptoms, but most of them are mild. Special education, behavioral therapy, and medications can help improve the prognosis.

Basic Information

Visiting department: Pediatrics
Whether inherited: Yes

Multiple people: Male patients are more common and have more severe symptoms, and about 1/3 of female carriers show mental retardation or other symptoms.

Causes of fragile X syndrome

Fragile X syndrome is an incompletely dominant X-linked dominant genetic disease. Its pathogenic gene is FMR1, which is highly expressed in nerve cells and testicular spermatogonia, and has selective RNA binding. The CGG trinucleotide repeat is contained in the exon 1 of the 5´ non-coding region of the gene. The abnormal amplification of CGG is the main cause of the intrinsic, accounting for 95% of the point mutations in the gene or 1 or 2 bases. The absence of a base can also lead to an intrinsic occurrence (<5%).

Clinical manifestations of fragile X syndrome

Mental retardation

Most male patients have IQs below 50, including low abilities in abstract thinking, reasoning, and concept formation. Some women with full mutations in the FMR1 gene have mild mental retardation, which is manifested by poor language expression and poor academic performance, especially in math and premature ovarian failure.

Language barrier

The age of speaking is delayed, and the expression ability is poor. Most patients have pathological imitation, repeated speech, and lack of vocabulary.

3. Changes in appearance

Narrow face, poor development in the middle of the face, prominent forehead, and mandibular protrusion. There are also special ear changes, such as big ears, eversion, ear swelling, single ear wheels, etc.

4. Behavioral disorders

Some children present with attention deficit hyperactivity disorder, hand swing, hand biting, overreaction, aggressive behavior, or autism.

5. Testicle enlargement

Most male patients have enlarged testicles after puberty, and a few can show giant testicles before puberty.

6. Other

Seizures can occur in 20% of children, and mitral valve prolapse and ascending aorta dilation in a small number of patients.

Fragile X syndrome test

Immunocytochemical detection

It has preliminary diagnostic significance. The mouse anti-FMRP monoclonal antibody is used to directly detect the number of FMRP positives in white blood cells to determine whether there is a decrease or absence of FMRP.

2. Fragile X chromosome analysis

Folic acid with low folic acid and low thymidine plus fluorouracil deoxynucleoside, methotrexate and other drugs can induce the expression of fragile X sites. Generally, 3% to 5% of cells express positive fragile X chromosomes.

3. CGG triplet repeat DNA analysis

The polymerase chain reaction is used to amplify DNA fragments, select restriction enzymes, and determine the length of repeat sequences for diagnosis by gel electrophoresis analysis, which can be used for prenatal diagnosis and carrier detection.

Fragile X syndrome diagnosis

Clinical manifestation

Males in the family showed clinical manifestations such as mental retardation, giant testis, big ears, and special facial features. It has been suggested to use a 10-point scoring method for 5 indicators (mental retardation with speech impairment, family history, behavioral disorders, big ears, face changes) to diagnose X-linked mental retardation (XLMR) patients. If the score is 8-10, the fragile X chromosome positive rate can reach 67%, and the diagnostic positive rate rises to 64.3%.

2. Laboratory inspection

The fragile X chromosome expression rate is> 3%. The fragile X chromosome is positive, and the CGG triplet repeat DNA analysis can confirm the diagnosis.

Differential diagnosis of fragile X syndrome

This disease needs to be distinguished from other causes of mental retardation, and karyotype analysis can help rule out other chromosome diseases.

Fragile X syndrome treatment

Drug treatment

It is mainly aimed at attention deficit and hyperactivity behavior. For children over 4 years old, brain stimulants such as methylphenidate are often used. Other drugs, such as selective serotonin reuptake inhibitors, can help improve hyperactivity, mood swings, aggressive behavior, and anger.

2. Other treatments

Boys with this disease all need speech and language rehabilitation to achieve the best development of language function. Special education and behavioral therapy can help improve patient behavior and quality of life.

Fragile X syndrome prevention

After the diagnosis, the first-degree relatives of the patient should be checked to detect the carrier of pre-mutation or full-mutation, and the offspring should be prevented through genetic counseling or prenatal diagnosis.