About 92% of pregnancies in Europe with a diagnosis of Down syndrome are terminated. In the United States, termination rates are around 67%, but this rate varied from 61% to 93% among different populations evaluated. When nonpregnant people are asked if they would have a termination if their fetus tested positive, 23–33% said yes, when high-risk pregnant women were asked, 46–86% said yes, and when women who screened positive are asked, 89–97% say yes.

Pre-implantation genetic diagnosis (PGD or PIGD) is a technique used to identify genetically normal embryos and is useful for couples who have a family history of genetic disorders. This is an option for people choosing to procreate through IVF. PGD is considered difficult due to it being both time consuming and having success rates only comparable to routine IVF.

Karyotyping involves performing an amniocentesis in order to study the cells of an unborn fetus during metophase 1. Light microscopy can be used to visually determine if aneuploidy is an issue.

Diagnosis of 22q11.2 deletion syndrome can be difficult due to the number of potential symptoms and the variation in phenotypes between individuals. It is suspected in patients with one or more signs of the deletion. In these cases a diagnosis of 22q11.2DS is confirmed by observation of a deletion of part of the long arm (q) of chromosome 22, region 1, band 1, sub-band 2. Genetic analysis is normally performed using fluorescence "in situ" hybridization (FISH), which is able to detect microdeletions that standard karyotyping (e.g. G-banding) miss. Newer methods of analysis include Multiplex ligation-dependent probe amplification assay (MLPA) and quantitative polymerase chain reaction (qPCR), both of which can detect atypical deletions in 22q11.2 that are not detected by FISH. qPCR analysis is also quicker than FISH, which can have a turn around of 3 to 14 days.

A 2008 study of a new high-definition MLPA probe developed to detect copy number variation at 37 points on chromosome 22q found it to be as reliable as FISH in detecting normal 22q11.2 deletions. It was also able to detect smaller atypical deletions that are easily missed using FISH. These factors, along with the lower expense and easier testing mean that this MLPA probe could replace FISH in clinical testing.

Genetic testing using BACs-on-Beads has been successful in detecting deletions consistent with 22q11.2DS during prenatal testing. Array-comparative genomic hybridization (array-CGH) uses a large number of probes embossed in a chip to screen the entire genome for deletions or duplications. It can be used in post and pre-natal diagnosis of 22q11.2.

Fewer than 5% of individuals with clinical symptoms of the 22q11.2 deletion syndrome have normal routine cytogenetic studies and negative FISH testing. In these cases, atypical deletions are the cause. Some cases of 22q11.2 deletion syndrome have defects in other chromosomes, notably a deletion in chromosome region 10p14.

Though the outcome for individuals with either form of the tetrasomy is highly variable, mosaic individuals consistently experience a more favourable outcome than those with the non-mosaic form. Some affected infants die shortly after birth, particularly those with the non-mosaic tetrasomy. Many patients do not survive to reproductive age, while others are able to function relatively normally in a school or workplace setting. Early diagnosis and intervention has been shown to have a strong positive influence on the prognosis.

The vast majority of triple X women are never diagnosed, unless they undergo tests for other medical reasons later in life. Triple X can be diagnosed by a blood test which is able to look at a person’s chromosomes (karyotype). Abnormalities on the electroencephalography may be present.

Triple X syndrome can be diagnosed prenatally through amniocentesis or chorionic villus sampling. In Denmark, between 1970 and 1984, 76% of the prenatally diagnosed fetuses with triple-X were aborted. Between 1985-1987, this figure dropped to 56%. With improved information, the number of abortions diminished. In the Netherlands, between 1991 and 2000, 33% (18/54) of the couples that were confronted with a prenatal diagnosis of 47, XXX elected to abort. If balanced information is provided to prospective parents, prenatally, the incidence of voluntary termination (abortion) is reduced.

The diagnosis can often be suspected based on the child's physical appearance at birth. An analysis of the child's chromosomes is needed to confirm the diagnosis, and to determine if a translocation is present, as this may help determine the risk of the child's parents having further children with Down syndrome. Parents generally wish to know the possible diagnosis once it is suspected and do not wish pity.

Diagnosis is usually based on clinical findings, although fetal chromosome testing will show trisomy 13. While many of the physical findings are similar to Edwards syndrome there are a few unique traits, such as polydactyly. However, unlike Edwards syndrome and Down syndrome, the quad screen does not provide a reliable means of screening for this disorder. This is due to the variability of the results seen in fetuses with Patau.

Diagnosis is based on the distinctive cry and accompanying physical problems. These common symptoms are quite easily observed in infants. Affected children are typically diagnosed by a doctor or nurse at birth. Genetic counseling and genetic testing may be offered to families with individuals who have cri du chat syndrome. Prenatally the deletion of the cri du chat related region in the p arm of chromosome 5 can be detected from amniotic fluid or chorionic villi samples with BACs-on-Beads technology. G-banded karyotype of a carrier is also useful. Children may be treated by speech, physical and occupational therapists. Heart abnormalities often require surgical correction.

Since tetrasomy 9p is not usually inherited, the risk of a couple having a second child with the disorder is minimal. While patients often do not survive to reproductive age, those who do may or may not be fertile. The risk of a patient's child inheriting the disorder is largely dependent on the details of the individual's case.

The duplication involved in PTLS is usually large enough to be detected through G-banding alone, though there is a high false negative rate. To ascertain the diagnosis when karyotyping results are unclear or negative, more sophisticated techniques such as subtelomeric fluorescent in-situ hybridization analysis and array comparative genomic hybridization (aCGH) may be used.

1. Clinical Genetics and Genetic Testing

Genetic testing is necessary to confirm the diagnosis of PMS. A prototypical terminal deletion of 22q13 can be uncovered by karyotype analysis, but many terminal and interstitial deletions are too small to detect with this method. Chromosomal microarray should be ordered in children with suspected developmental delays or ASD. Most cases will be identified by microarray; however, small variations in genes might be missed. The falling cost for whole exome sequencing may replace DNA microarray technology for candidate gene evaluation. Biological parents should be tested with fluorescence "in situ" hybridization (FISH) to rule out balanced translocations or inversions. Balanced translocation in a parent increases the risk for recurrence and heritability within families (figure 3).

Clinical genetic evaluations and dysmorphology exams should be done to evaluate growth, pubertal development, dysmorphic features (table 1) and screen for organ defects (table 2)

2. Cognitive and Behavioral Assessment

All patients should undergo comprehensive developmental, cognitive and behavioral assessments by clinicians with experience in developmental disorders. Cognitive evaluation should be tailored for individuals with significant language and developmental delays. All patients should be referred for specialized speech/language, occupational and physical therapy evaluations.

3. Neurological Management

Individuals with PMS should be followed by a pediatric neurologist regularly to monitor motor development, coordination and gait, as well as conditions that might be associated with hypotonia. Head circumference should be performed routinely up until 36 months. Given the high rate of seizure disorders (up to 41% of patients) reported in the literature in patients with PMS and its overall negative impact on development, an overnight video EEG should be considered early to rule out seizure activity. In addition, a baseline structural brain MRI should be considered to rule out the presence of structural abnormalities.

4. Nephrology

All patients should have a baseline renal and bladder ultrasonography and a voiding cystourethrogram should be considered to rule out structural and functional abnormalities. Renal abnormalities are reported in up to 38% of patients with PMS. Vesicouretral reflux, hydronephrosis, renal agenesis, dysplasic kidney, polycystic kidney and recurrent urinary tract infections have all been reported in patients with PMS.

5. Cardiology

Congenital heart defects (CHD) are reported in samples of children with PMS with varying frequency (up to 25%)(29,36). The most common CHD include tricuspid valve regurgitation, atrial septal defects and patent ductus arteriousus. Cardiac evaluation, including echocardiography and electrocardiogram, should be considered.

6. Gastroenterology

Gastrointestinal symptoms are common in individuals with PMS. Gastroesophageal reflux, constipation, diarrhea and cyclic vomiting are frequently described.

Table 3: Clinical Assessment Recommendations in Phelan McDermid Syndrome.

More than 80% of children with Patau syndrome die within the first year of life. Children with the mosaic variation are usually affected to a lesser extent. In a retrospective Canadian study of 174 children with trisomy 13, median survival time was 12.5 days. One and ten year survival was 19.8% and 12.9% respectively.

Trisomy 9 can be detected prenatally with chorionic villus sampling and cordocentesis, and can be suggested by obstetric ultrasonography.

Because trisomy 9 may appear with mosaicism, it is suggested that doctors take samples from multiple tissues when karyotyping for diagnosis.

Since the symptoms caused by this disease are present at birth, there is no “cure.” The best cure that scientists are researching is awareness and genetic testing to determine risk factors and increase knowledgeable family planning. Prevention is the only option at this point in time for a cure.

Emanuel Syndrome can be diagnosed with a karyotype, with FISH, or with a chromosomal microarray analysis. .

22q11.2 deletion syndrome was estimated to affect between one in 2000 and one in 4000 live births. This estimate is based on major birth defects and may be an underestimate, because some individuals with the deletion have few symptoms and may not have been formally diagnosed. It is one of the most common causes of mental retardation due to a genetic deletion syndrome.

The prevalence of 22q11.2DS has been expected to rise because of multiple reasons: (1) Thanks to surgical and medical advances, an increasing number of people are surviving heart defects associated with the syndrome. These individuals are in turn having children. The chances of a 22q11.2DS patient having an affected child is 50% for each pregnancy; (2) Parents who have affected children, but who were unaware of their own genetic conditions, are now being diagnosed as genetic testing become available; (3) Molecular genetics techniques such as FISH (fluorescence in situ hybridization) have limitations and have not been able to detect all 22q11.2 deletions. Newer technologies have been able to detect these atypical deletions.

Recently, the syndrome has been estimated to affect up to one in 2000 live births. Testing for 22q11.2DS in over 9500 pregnancies revealed a prevalence rate of 1/992.

Emanuel Syndrome does not have a cure, but individual symptoms may be treated. Assessments of individual systems, such as the cardiovascular, gastrointestinal, orthopedic, and neurological may be necessary to determine the extent of impairment and options for treatment.

Because the variability of this disease is so great and the way that it reveals itself could be multi-faceted; once diagnosed, a multidisciplinary team is recommended to treat the disease and should include a craniofacial surgeon, ophthalmologist, pediatrician, pediatric urologist, cardiologist, pulmonologist, speech pathologist, and a medical geneticist. Several important steps must be followed, as well.

- Past medical history

- Physical examination with special attention to size and measurements of facial features, palate, heart, genitourinary system and lower respiratory system

- Eye evaluation

- Hypospadias assessment by urologist

- Laryngoscopy and chest x-ray for difficulties with breathing/swallowing

- Cleft lip/palate assessment by craniofacial surgeon

- Assessment of standard age developmental and intellectual abilities

- Anal position assessment

- Echocardiogram

- Cranial imaging

Many surgical repairs may be needed, as assessed by professionals. Furthermore, special education therapies and psychoemotional therapies may be required, as well. In some cases, antireflux drugs can be prescribed until risk of breathing and swallowing disorders are removed. Genetic counseling is highly advised to help explain who else in the family may be at risk for the disease and to help guide family planning decisions in the future.

Because of its wide variability in which defects will occur, there is no known mortality rate specifically for the disease. However, the leading cause of death for people with Opitz G/BBB syndrome is due to infant death caused by aspiration due to esophageal, pharyngeal or laryngeal defects.

Fortunately, to date there are no factors that can increase the expression of symptoms of this disease. All abnormalities and symptoms are present at birth.

During pregnancy, women can be screened by chorionic villus sampling and amniocentesis to detect trisomy 16. With the advent of noninvasive techniques for detecting aneuploidy, prenatal screening with tests using Next Generation Sequencing can be utilised prior to invasive techniques. This can cause fetal growth retardation.

The general prognosis for girls with tetrasomy X is relatively good. Due to the variability of symptoms, some tetrasomy X girls are able to function normally, whereas others will need medical attention throughout their lives. Traditionally, treatment for tetrasomy X has been management of the symptoms and support for learning. Most girls are placed on estrogen treatment to induce breast development, arrest longitudinal growth, and stimulate bone formation to prevent osteoporosis. Speech, occupational, and physical therapy may also be needed depending on the severity of the symptoms.

Edwards syndrome occurs in about one in 5,000 live births, but more conceptions are affected by the syndrome because the majority of those diagnosed with the condition prenatally will not survive to birth. Although women in their 20s and early 30s may conceive babies with Edwards syndrome, the risk of conceiving a child with it increases with a woman's age. The average maternal age for conceiving a child with this disorder is 32½.

Triploidy may be suggested by dramatically elevated levels of serum alpha-fetoprotein. On obstetric ultrasonography, abnormalities of the skeleton, central nervous system, heart, abdomen, and kidneys are visible in the most severe cases beginning at 12-14 weeks of pregnancy. Placental abnormalities associated with a triploid pregnancy become visible at 12-14 weeks. Placentomegaly or intrauterine growth restriction are the typical findings that prompt evaluation for triploidy, though oligohydramnios may be the first sign in some cases. Placentomegaly is not pathognomonic for triploidy because in some cases, the placenta senesces.

Triploidy must be distinguished from trisomy 13 and trisomy 18, which may appear similar on sonography. Genetic testing allows for a definitive diagnosis.

Several researchers around the world are studying on the subject of 1q21.1 duplication syndrome. The syndrome was identified for the first time in people with heart abnormalities. The syndrome was later observed in patients who had autism or schizophrenia.

It appears that there is a relation between autism and schizophrenia. Literature shows that nine locations have been found on the DNA where the syndromes related to autism or schizophrenia can be found, the so-called "hotspots": 1q21.1, 3q29, 15q13.3, 16p11.2, 16p13.1, 16q21, 17p12, 21q11.2 and 21q13.3. With a number of hotspots both autism and schizophrenia were observed at that location. In other cases, either autism or schizophrenia has been seen, while they are searching for the opposite.

Statistical research showed that schizophrenia is significantly more common in combination with 1q21.1 deletion syndrome. On the other side, autism is significantly more common with 1q21.1 duplication syndrome. Similar observations were done for chromosome 16 on 16p11.2 (deletion: autism/duplication: schizophrenia), chromosome 22 on 22q11.21 (deletion (Velo-cardio-facial syndrome): schizophrenia/duplication: autism) and 22q13.3 (deletion (Phelan-McDermid syndrome): schizophrenia/duplication: autism). Further research confirmed that the odds on a relation between schizophrenia and deletions at 1q21.1, 3q29, 15q13.3, 22q11.21 en Neurexin 1 (NRXN1) and duplications at 16p11.2 are at 7.5% or higher.

Common variations in the BCL9 gene, which is in the distal area, confer risk of schizophrenia and may also be associated with bipolar disorder and major depressive disorder.

Research is done on 10-12 genes on 1q21.1 that produce DUF1220-locations. DUF1220 is an unknown protein, which is active in the neurons of the brain near the neocortex. Based on research on apes and other mammals, it is assumed that DUF1220 is related to cognitive development (man: 212 locations; chimpanzee: 37 locations; monkey: 30 locations; mouse: 1 location). It appears that the DUF1220-locations on 1q21.1 are in areas that are related to the size and the development of the brain. The aspect of the size and development of the brain is related to autism (macrocephaly) and schizophrenia (microcephaly). It is assumed that a deletion or a duplication of a gene that produces DUF1220-areas might cause growth and development disorders in the brain

Another relation between macrocephaly with duplications and microcephaly with deletions has been seen in research on the HYDIN Paralog or HYDIN2. This part of 1q21.1 is involved in the development of the brain. It is assumed to be a dosage-sensitive gene. When this gene is not available in the 1q21.1 area it leads to microcephaly. HYDIN2 is a recent duplication (found only in humans) of the HYDIN gene found on 16q22.2.

GJA5 has been identified as the gene that is responsible for the phenotypes observed with congenital heart diseases on the 1q21.1 location. In case of a duplication of GJA5 tetralogy of Fallot is more common. In case of a deletion other congenital heart diseases than tetralogy of Fallot are more common.

The ring 20 abnormality may be limited to as few as 5% of cells, so a screen for chromosomal mosaicism is critical. Newer array technology will not detect the ring chromosome and the standard metaphase chromosome analysis has been recommended. A karyotype analysis examining at least 50 cells should be requested to properly detect mosaicism.