Mechanism and inheritance
The FMR1 gene contains a region with a repeating sequence of three nucleotides. Normally, there are few such repetitions. When their number increases to intermediate values, they speak of a premutation, and with a significant increase, they speak of a complete mutation, in which the gene is turned off. The premutation can expand during transmission from mother to child, so a healthy carrier woman can give birth to a child with the full mutation. Men with the premutation pass it on to all their daughters, but not to their sons. Boys with a complete mutation do not have a second X chromosome that can compensate for the defect, so the manifestations are more pronounced than in girls.
- Increase in the number of repeats in the FMR1 gene
- A premutation in the mother can expand in the offspring
- A complete mutation turns off a gene
- Boys suffer more than girls
- Fathers pass on the premutation only to daughters
- Premutation carriers have their own health problems
Signs in children
At an early age, developmental delay comes to the fore: the child begins to sit and walk later, speech appears late and remains poor. Behavioral features are noticeable - avoidance of gaze, shaking of hands, repetitive actions, intolerance to noise and touch, severe anxiety in a new environment. Many children are diagnosed with autism spectrum disorder and may co-occur with this syndrome. External features become more distinct with age: an elongated face, large protruding ears, a high palate, flexible joints, flat feet.
- Delayed speech and motor development
- Avoidance of eye contact, anxiety
- Repetitive movements and stereotypies
- Increased sensitivity to noise and touch
- Hyperactivity and difficulty concentrating
- Long face, large ears, high palate
- Joint hypermobility, flat feet
- Seizures occur in approximately some children
Features of girls and carriers
In girls with a complete mutation, the second, unchanged X chromosome partially compensates for the defect, so the manifestations are milder: learning difficulties are more common, especially with mathematics, shyness, anxiety and social difficulties with intact or borderline intelligence. A separate topic is premutation carriers who consider themselves healthy. Women with the premutation have an increased risk of early ovarian failure and menopause earlier than usual, and older male carriers may develop tremors and balance disorders. Therefore, family counseling is important not only for the sake of children.
- In girls, manifestations are milder and more variable
- Learning difficulties with intact intelligence
- Anxiety and social shyness
- Early ovarian failure in women with premutation
- Tremor and ataxia in older male carriers
- The need to examine relatives
Diagnostics
Conventional karyotyping does not reliably detect this syndrome, so a molecular genetic study is used, which determines the exact number of repeats in the FMR1 gene and the state of its activity. The analysis is taken from the blood. The examination is indicated for children with developmental delay of unknown cause, with autism, as well as in family cases of mental retardation. At the same time, developmental level, hearing and vision are assessed, since their impairments can aggravate speech delay. For seizures, electroencephalography is prescribed. The geneticist explains the result and assesses the risk to other family members.
- Molecular genetic study of the FMR1 gene
- Assessment of psycho-speech development by a specialist
- Hearing and vision testing
- Electroencephalography for seizures
- Examination of mother and relatives for carrier status
- Consultation with a geneticist on family planning
Helping a child
There is no drug yet that restores the functioning of the gene, so the basis remains early and regular developmental intervention. Classes with a speech therapist and speech pathologist, behavioral therapy, training in self-care and communication skills give the best results when started in the first years of life. A predictable daily routine, visual cues, and a quiet environment without excessive noise are helpful. Medicines are used in a targeted manner to reduce severe anxiety, hyperactivity or seizures, and are prescribed only by a doctor. Support and training in how to interact with the child are important for the family.
- Early intervention and sessions with a speech therapist
- Behavioral therapy and communication skills development
- Predictable mode and visual cues
- Reducing sensory overload
- Medications for anxiety and seizures
- Individual educational route
- Parent support and training
- Observation by a geneticist when planning subsequent children