Trisomy 14 is the result of a genomic mutation. Symptoms depend on the type of mutation. Often, trisomy 14 causes miscarriages, according to studies.
What is trisomy 14?
There is a difference between gene mutations and genomic mutations. In gene mutations, certain nucleotides are missing, some nucleotides are switched, or additional nucleotides are added. In a genomic mutation, the entire genome is affected. Thus, additional chromosomes are present or chromosomes are missing or interchanged. Such an altered number of chromosomes is the basis of trisomy 14. This is a complex of disabilities caused by the triple execution of the hereditary material on chromosome 14. In a healthy person, chromosome 14 is present in duplicate. Therefore, a triple execution corresponds to a genomic mutation. Trisomy 14 exists in different variants and shows variable clinical symptoms depending on the subtype. In addition to mosaic and partial trisomy 14, medicine recognizes a so-called translocation trisomy 14 and a free form of the disease. These subtypes are based on different types of mutation. Partial trisomy 14 is most frequently observed in living organism. Since its initial description, only slightly more than 20 case reports have been documented in living patients.
Causes
Genome mutations originate in genetic material. In mosaic trisomy 14, not all cells of chromosome 14 are present in triplicate. At the same time as the trisomal cell line, a cell line with a diploid set exists. Thus, several karyotypes are present at the same time. In partial trisomy 14, two sets of chromosome 14 are present in all cells except the germ cells. However, because one of the chromosomes is elongated and divided into two in a certain section, some of the genetic information is still present in triplicate. In translocation trisomy 14, chromosome 14 is present in all cells with triple execution. One version of the three chromosomes attaches itself completely or partially to one of the other two chromosomes and translocates in this way. Free trisomy 14 is also based on the triple execution of chromosome 14 in all cells of the body. However, displacement does not take place in this form. According to current knowledge, girls are more often affected by trisomy 14 than boys. Most fetuses with trisomy 14 die during pregnancy. This association often underlies early miscarriages. Of 776 miscarried fetuses, 15 suffered from trisomy 14, according to one study.
Symptoms, complaints, and signs
In trisomy 14, clinical symptoms depend on the percentage of trisomeric cells or are determined by the trisomal chromosomal segment present. For this reason, symptomatic generalizations are difficult to make. Abnormally high amniotic fluid volumes are often seen in women with affected fetuses during pregnancy. Prematurity before the 37th week of gestation is also among the most common manifestations. Even in the womb, fetuses often suffer from delayed growth. After birth, psychomotor delays in development are added. Growth is often asymmetrical. Displaced hips or limbs with different sides may occur. The fingers or toes of affected individuals often overlap. Organic defects such as heart defects may be present. In addition to microcephaly, facial deformities such as a wide forehead or low-set ears, a wide bridge of the nose, or facial asymmetries are often present. Facial symptoms may also include a long philtrum, cleft palate, abnormal palatal curvature, and a small lower jaw with a simultaneously protruding upper jaw. The same is true for a large mouth opening, unusually full lips, and deep-set small, widely spaced eyes. Patients also often have narrow palpebral fissures and slightly drooping upper eyelids. There is a translucent film on the eyes in many cases. The patients’ skin is often hyperpigmented. The most common genitourinary tract changes include an abnormally small penis and undescended testis. These symptoms are often associated with renal failure and cognitive impairment.
Diagnosis and disease course
Prenatally, fetuses with trisomy 14 already show abnormalities on ultrasound, which may be a sign of the trisomy to the gynecologist.The free form and the mosaic form of the disease can essentially be diagnosed beyond doubt by invasive diagnostic methods, primarily with the aid of amniocentesis or chorionic villus sampling. However, chorionic villus sampling is considered error-prone and may result in a false positive diagnosis. A postnatal suspected diagnosis is already established by the characteristic physical features of the patient and is usually confirmed or ruled out by molecular genetic analysis. The prognosis depends on the particular mutation and symptoms in each individual case.
Complications
Trisomy 14 is associated with various symptoms, all of which have a very negative impact on the quality of life of the affected person. First and foremost, there is significantly delayed growth and equally delayed development of the patient. The disease can therefore already be diagnosed in the womb. Furthermore, those affected suffer from a cleft palate, so that complications can arise when taking food and liquids. Heart defects also occur frequently due to trisomy 14 and can also negatively affect the life expectancy of the child as a result. Due to the facial malformations, many affected individuals suffer from bullying or teasing, especially in childhood, and may suffer from psychological upsets as a result. Kidney insufficiency can also occur, so that in the worst case patients are dependent on dialysis or a donor kidney. Since trisomy 14 also leads to mental retardation and thus to cognitive and motor impairments, those affected are usually dependent on the help of other people in their daily lives. Since there is no direct treatment, there are no particular complications. Only the individual complaints are alleviated by various therapies. In many cases, the parents and relatives are also dependent on psychological treatment.
When should one go to the doctor?
In the case of trisomy 14, a visit to a doctor is definitely necessary. It can come with this disease without treatment to the death of the affected person, so an examination and subsequent treatment must be carried out in any case. In the process, self-healing may not occur either. Early detection of trisomy 14 always has a very positive effect on the further course of the disease. A doctor should be consulted for trisomy 14 if the affected person suffers from malformations or deformities that can affect the entire body. In many cases, defects in the heart may also indicate the condition and should be checked by a doctor. In this case, insufficiency of the kidneys also often indicates trisomy 14. Since the disease cannot be treated completely, the relatives and parents of the affected person are often dependent on psychological treatment to prevent depression or further psychological upsets. The treatment of the affected person itself depends strongly on the exact symptoms and is carried out by the respective specialist. In case of a renewed desire to have children, genetic counseling should be performed.
Treatment and therapy
For patients with trisomy 14, no causal therapy is available to date. Only gene therapy approaches could be considered as causal therapy. However, these approaches have not yet reached the clinical phase. For this reason, trisomy is currently treated exclusively symptomatically. Accordingly, the treatment depends on the symptoms in the individual case. The organic deformities and insufficiencies are the focus of therapy. The heart defect, for example, is corrected as early as possible in an invasive surgical procedure. Renal insufficiency in children also requires early intervention, which may initially consist of dialysis. In the long run, kidney transplantation is the most reasonable way of treatment. Facial deformities do not necessarily require treatment. Therefore, they are often disregarded initially. More important is an early support for the cognitive improved development of the children and a physiotherapeutic support of the motor skills. Since not all patients with trisomy 14 present with symptoms such as a heart defect, delayed development or renal insufficiency, some affected individuals are relatively asymptomatic throughout their lives and then do not require therapy.
Prevention
Because trisomy 14 is a genetic mutation, there are few preventive measures available. Because prenatal diagnosis is possible, parents of affected fetuses may decide not to have the child if necessary.
Follow-up
Live-born children with trisomy 14 benefit from remedial early intervention. This should be adapted to the child’s individual abilities. Because this chromosomal disorder in the living patient is usually a partial trisomy or a mosaic trisomy, the clinical picture also varies widely. Thus, the physical symptoms also require individual assessment and follow-up. While in some cases the main goal is to prevent pain and suffering, others affected may be able to successfully learn various daily living skills. Children with a free trisomy 14 die in the vast majority of cases already in the womb. Such a miscarriage is stressful for the affected parents, which may require psychological aftercare. How long this lasts depends on the wishes of the parents and the individual situation. Human genetics is consulted in an attempt to clarify the cause of the genetic defect. In this way, the risk of recurrence can also be better estimated. In most cases, this is not significantly increased. In the case of a subsequent pregnancy, an amniocentesis or chorionic villus sampling can be performed at the mother’s request. This can detect a recurrence of trisomy 14 already during pregnancy. However, these tests also increase the risk of miscarriage.
What you can do yourself
The symptomatic treatment of trisomy 14, which includes surgery, medication and physiotherapy, can be effectively supported by a whole range of self-help measures. First of all, it is important to support the affected child as best as possible in everyday life. Physiotherapy and mental training can also be carried out away from inpatient therapy. It is best for parents to talk to a specialist who can recommend suitable measures to correct the individual malformations as best as possible. Talk therapy is also useful for the child. Younger children in particular ask many questions about their condition that cannot always be answered by the parents themselves. Therefore, an expert must be consulted to explain the child in the best possible way. Child-friendly books about the hereditary disease additionally help to build up a healthy relationship to the disease. In addition, parents must keep a close eye on the child so that a quick response can be made in case of complications. The home must be equipped for the disabled so that there is no risk from falls or accidents. In addition, suitable special schools and kindergartens should be sought for the sick child at an early stage, as registration periods often last several years.
