Trisomy 8 is a genomic mutation that results in chromosomal aberration. Symptoms depend on the form of the mutation. Many trisomy eight patients have a mild course with relatively normal intelligence.
What is trisomy eight?
Trisomy 8 is a rare chromosomal abnormality that results from a genomic mutation and occurs sporadically. The condition is also known as Warkany syndrome 2, a name given to it by pediatrician Joseph Warkany, who first described the symptom complex in the 20th century. Since his initial description, only about 120 cases of trisomy 8 have been documented. Chromosome eight trisomy is predominantly in the form of a mosaic mutation and affects both boys and girls. The symptoms are sometimes already clearly pronounced before birth and show up in the prenatal ultrasound. Trisomy is always said to occur when there are three copies of the genes instead of two. The symptoms of trisomy eight depend, on the one hand, on the affected section of the chromosome and, on the other hand, on the completeness of the trisomy and thus the respective subtype of the causative mutation. Severe trisomies are often associated with pregnancy loss. Thus, the affected fetus is not capable of survival in a severe form of trisomy.
Causes
The primary cause of trisomy eight, as with any other trisomy, is a genomic mutation. To be distinguished from this are gene mutations that do not change the number of chromosomes within individual body cells. Gene mutations change the structure of the DNA because the sequence of the building blocks is altered. In genomic mutations, on the other hand, the genetic material itself is altered and exhibits an abnormal set of chromosomes. An entire set of chromosomes may be missing from individual cells, incorrectly arranged, or present in multiplied form. The genomic mutation results from defective cell division during the first or second maturation division in meiosis. This type of mutation may correspond to a partial mutation and in this case does not affect the entire genome. The mutation may also correspond to a translocation and then results in the adhesion of an additional set of chromosomes present to one of the other sets of chromosomes. If, on the other hand, there is a mosaic mutation of the genome, two sister chromatids have not separated during mitosis and the trisomy is confined to certain cells of the body, while a normal set of chromosomes is present in other cells.
Symptoms, symptoms, and signs
Many symptoms of trisomy 8 are apparent before birth. In addition to a heart defect and malformation of the kidneys, these symptoms include, for example, widening of the renal pelvis, tetramelia, and scoliosis, lordosis, or kyphosis. Block vertebrae, clinodactyly and camptodactyly can also be detected prenatally. The same applies to the characteristic mandibular retrognathia, brachydactyly or hypoplasia of the patella. The clinical picture is extremely variable, especially after birth, and depends mainly on the form of the trisomy. Generalizations are almost impossible. Common symptoms are arthrogryposis, a so-called spina bifida occulta and abnormal plantar furrows or a sandal furrow, palmar furrows and four-finger furrows. Affected individuals often have low-set and large or long ears. Their anthelix is often underdeveloped. The forehead is high in many cases. In addition to a short neck, narrow sloping shoulders may be present. The rib cage is often exceptionally long. The number and thickness of the ribs is abnormal. Associated with these symptoms may be accessory nipples, a gothic palate, or a cleft palate. Exceptionally full lips and an inverted lower lip are part of the clinical picture as well as hypotelorism, ptosis or strabismus. In most cases, mild to moderate cognitive impairment is also present. Despite this long list of symptoms, there are trisomy patients who are virtually asymptomatic throughout their lives.
Diagnosis and course of the disease
The diagnosis of trisomy 8 can be made prenatally. Fine ultrasound provides the first clues. However, a prenatally certain diagnosis can only be made by analysis of the chromosomes. Prenatal amniocentesis or chorionic villus sampling can be performed for this purpose.However, mosaic trisomy 8 in particular may also be subject to local limitation. All prenatal diagnoses of trisomy are considered uncertain and often result in false positives. Postnatally, the diagnosis can be made on suspicion depending on the clinical picture. Genetic analysis confirms or excludes the suspected diagnosis. Prognosis depends on the proportion of trisomeric and disomeric cells. Mental and physical development often correlate during the course of the disease. Normal development may be conceivable in mild trisomy 8.
When should you see a doctor?
Medical treatment is definitely needed for trisomy 8. The affected person depends on early detection of the disease so that further complications and discomfort can be prevented. The earlier trisomy 8 is detected, the better is usually the further course of this disease. A doctor should be contacted if the affected person suffers from a heart defect. This should always be controlled by regular examinations. Furthermore, limitations in intelligence can also indicate the disease and should be checked by a doctor. Some patients also suffer from strabismus or other visual problems and are therefore unable to participate in everyday life without difficulty. Psychological upsets or even depression may also be indicative of this disease. In the case of trisomy 8, a general practitioner or a pediatrician should be consulted. However, further treatment also requires a visit to a specialist to properly treat the symptoms.
Treatment and therapy
Trisomy 8 remains one of the incurable diseases to date. Causal therapy is basically not available for trisomy patients, as any gene therapies have not yet been approved for treatment. Incurable diseases can ultimately only be alleviated by symptomatic therapy. This symptomatic therapy depends on the symptoms present in each individual case. The focus of therapy is primarily on deformities and loss of function of vital organs. In the case of trisomy 8, therefore, the heart defect initially receives the greatest attention. Surgical intervention can sometimes correct existing heart defects. Agnosia of the patella can be corrected by reconstructive surgery to restore normal range of motion. Fluid collections in the neck can be drained, and kidney deformities with functional limitations of the kidneys are treated via dialysis and later transplantation if necessary. Deformities of the face and fingers or toes can also be resolved surgically. However, this approach is not mandatory and does not have to take place immediately after birth. More important is early intervention with the goal of mentally normal development. In mild forms of trisomy eight, intelligence is usually not strikingly impaired, and patients may not need to undergo surgical therapy steps.
Prevention
Preventive measures are not available for trisomy 8. However, after a prenatal diagnosis, parents may choose not to have the child.
Follow-up
Follow-up care for trisomy 8 is multifaceted. This is because some of the patients’ symptoms differ significantly. While some of the affected children have severe intellectual disabilities and require lifelong care, other patients are only mildly mentally impaired or even completely unremarkable. However, almost all children with trisomy 8 benefit from early intervention with occupational therapy and other measures. Follow-up care does not only include the treatment of the actual patients. The relatives should also be closely involved. Parents sometimes need support from a home help or a nursing service, as caring for their own child can be very stressful. Psychological support may also be appropriate in some cases. If the parents of a child with trisomy 8 have a desire to have another child, there is often concern that the defect may recur. Therefore, comprehensive follow-up includes counseling of the parents by a human geneticist. Although the risk of recurrence is usually low, existing fears should be taken seriously.If pregnancy occurs again, a chorionic villus sampling or amniocentesis can be performed to determine whether a chromosomal disorder is present. However, such an intervention poses an increased risk of miscarriage and should therefore be carefully considered.
What you can do yourself
People with trisomy 8 need permanent support in everyday life. It is the task of relatives and acquaintances to support the affected person in everyday life and help him with everyday tasks. This includes not only aspects such as personal hygiene or getting around, but also emotional support. Because trisomy 8 is associated with severe mental illness, depending on its severity, discussions may need to be held with therapists and self-help groups may need to be consulted. Reduced intelligence can be partially compensated for by cognitive training. Brain jogging, autogenic training, and a number of other measures that promote intelligence and encourage healthy behavior are effective. In the case of external malpositions, surgical measures must be taken. This must be initiated at an early stage so that physical development can proceed as normally as possible. Parents of affected children are best advised to contact the relevant specialist. People with trisomy 8 usually require specialist care in an institution. Psychological symptoms can be treated with medication, talk therapy, distraction and a number of other measures. The Association for Trisomy Patients provides affected individuals and their families with more information about the condition and points of contact for further counseling.