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.

Carrier testing for Roberts syndrome requires prior identification of the disease-causing mutation in the family. Carriers for the disorder are heterozygotes due to the autosomal recessive nature of the disease. Carriers are also not at risk for contracting Roberts syndrome themselves. A prenatal diagnosis of Roberts syndrome requires an ultrasound examination paired with cytogenetic testing or prior identification of the disease-causing ESCO2 mutations in the family.

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.

When screening tests predict a high risk of Down syndrome, a more invasive diagnostic test (amniocentesis or chorionic villus sampling) is needed to confirm the diagnosis. If Down syndrome occurs in one in 500 pregnancies and the test used has a 5% false-positive rate, this means, of 26 women who test positive on screening, only one will have Down syndrome confirmed. If the screening test has a 2% false-positive rate, this means one of eleven who test positive on screening have a fetus with DS. Amniocentesis and chorionic villus sampling are more reliable tests, but they increase the risk of miscarriage between 0.5 and 1%. The risk of limb problems is increased in the offspring due to the procedure. The risk from the procedure is greater the earlier it is performed, thus amniocentesis is not recommended before 15 weeks gestational age and chorionic villus sampling before 10 weeks gestational age.

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.

The diagnosis of this syndrome can be made on clinical examination and perinatal autopsy.

Koenig and Spranger (1986) noted that eye lesions are apparently nonobligatory components of the syndrome. The diagnosis of Fraser syndrome should be entertained in patients with a combination of acrofacial and urogenital malformations with or without cryptophthalmos. Thomas et al. (1986) also emphasized the occurrence of the cryptophthalmos syndrome without cryptophthalmos and proposed diagnostic criteria for Fraser syndrome. Major criteria consisted of cryptophthalmos, syndactyly, abnormal genitalia, and positive family history. Minor criteria were congenital malformation of the nose, ears, or larynx, cleft lip and/or palate, skeletal defects, umbilical hernia, renal agenesis, and mental retardation. Diagnosis was based on the presence of at least 2 major and 1 minor criteria, or 1 major and 4 minor criteria.

Boyd et al. (1988) suggested that prenatal diagnosis by ultrasound examination of eyes, digits, and kidneys should detect the severe form of the syndrome. Serville et al. (1989) demonstrated the feasibility of ultrasonographic diagnosis of the Fraser syndrome at 18 weeks' gestation. They suggested that the diagnosis could be made if 2 of the following signs are present: obstructive uropathy, microphthalmia, syndactyly, and oligohydramnios. Schauer et al. (1990) made the diagnosis at 18.5 weeks' gestation on the basis of sonography. Both the female fetus and the phenotypically normal father had a chromosome anomaly: inv(9)(p11q21). An earlier born infant had Fraser syndrome and the same chromosome 9 inversion.

Van Haelst et al. (2007) provided a revision of the diagnostic criteria for Fraser syndrome according to Thomas et al. (1986) through the addition of airway tract and urinary tract anomalies to the major criteria and removal of mental retardation and clefting as criteria. Major criteria included syndactyly, cryptophthalmos spectrum, urinary tract abnormalities, ambiguous genitalia, laryngeal and tracheal anomalies, and positive family history. Minor criteria included anorectal defects, dysplastic ears, skull ossification defects, umbilical abnormalities, and nasal anomalies. Cleft lip and/or palate, cardiac malformations, musculoskeletal anomalies, and mental retardation were considered uncommon. Van Haelst et al. (2007) suggested that the diagnosis of Fraser syndrome can be made if either 3 major criteria, or 2 major and 2 minor criteria, or 1 major and 3 minor criteria are present in a patient.

Genetic testing may be available for mutations in the FGDY1 gene. Genetic counseling is indicated for individuals or families who may carry this condition, as there are overlapping features with fetal alcohol syndrome.

Other examinations or tests can help with diagnosis. These can include:

detailed family history

- conducting a detailed physical examination to document morphological features

- testing for genetic defect in FGDY1

- x-rays can identify skeletal abnormalities

- echo cardiogram can screen for heart abnormalities

- CT scan of the brain for cystic development

- X-ray of the teeth

- Ultrasound of abdomen to identify undescended testis

Screening generally only takes place among those displaying several of the symptoms of ABCD, but a study on a large group of institutionalized deaf people in Columbia revealed that 5.38% of them were Waardenburg patients. Because of its rarity, none of the patients were diagnosed with ABCD (Waardenburg Type IV). Nothing can be done to prevent the disease.

Cytogenetic preparations that have been stained by either Giemsa or C-banding techniques will show two characteristic chromosomal abnormalities. The first chromosomal abnormality is called premature centromere separation (PCS) and is the most likely pathogenic mechanism for Roberts syndrome. Chromosomes that have PCS will have their centromeres separate during metaphase rather than anaphase (one phase earlier than normal chromosomes). The second chromosomal abnormality is called heterochromatin repulsion (HR). Chromosomes that have HR experience separation of the heterochromatic regions during metaphase. Chromosomes with these two abnormalities will display a "railroad track" appearance because of the absence of primary constriction and repulsion at the heterochromatic regions. The heterochromatic regions are the areas near the centromeres and nucleolar organizers. Carrier status cannot be determined by cytogenetic testing. Other common findings of cytogenetic testing on Roberts syndrome patients are listed below.

- Aneuploidy- the occurrence of one or more extra or missing chromosomes

- Micronucleation- nucleus is smaller than normal

- Multilobulated Nuclei- the nucleus has more than one lobe

The occurrence of WS has been reported to be one in 45,000 in Europe. The diagnosis can be made prenatally by ultrasound due to the phenotype displaying pigmentary disturbances, facial abnormalities, and other developmental defects. After birth, the diagnosis is initially made symptomatically and can be confirmed through genetic testing. If the diagnosis is not made early enough, complications can arise from

Hirschsprung's disease.

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.

In terms of diagnosing Bannayan–Riley–Ruvalcaba syndrome there is no current method outside the physical characteristics that may be present as signs/symptoms. There are, however, multiple molecular genetics tests (and cytogenetic test) to determine Bannayan–Riley–Ruvalcaba syndrome.

The diagnosis of Perlman syndrome is based on observed phenotypic features and confirmed by histological examination of the kidneys. Prenatal diagnosis is possible for families that have a genetic disposition for Perlman syndrome although there is no conclusive laboratory test to confirm the diagnosis. Fetal overgrowth, particularly with an occipitofrontal circumference (OFC) greater than the 90th centile for gestational age, as well as an excess of amniotic fluid in the amniotic sac (polyhydramnios), may be the first signs of Perlman. Using ultrasound diagnosis, Perlman syndrome has been detected at 18 weeks. During the first trimester, the common abnormalities of the syndrome observed by ultrasound include cystic hygroma and a thickened nuchal lucency. Common findings for the second and third trimesters include macrosomia, enlarged kidneys, renal tumors (both hamartoma and Wilms), cardiac abnormalities and visceromegaly.

Prompt recognition and identification of the disorder along with accurate follow-up and clinical assistance is recommended as the prognosis for Perlman is severe and associated with a high neonatal death rate.

Diagnosis of 48, XXXY is usually done by a standard karyotype. A karyotype is a chromosomal analysis in which a full set of chromosomes can be seen for an individual. The presence of the additional 2 X chromosomes on the karyotype are indicative of XXXY syndrome.

Another way to diagnosis 48, XXXY is by chromosomal microarray showing the presence of extra X chromosomes. Chromosomal microarray (CMA) is used to detect extra or missing chromosomal segments or whole chromosomes. CMA uses microchip-based testing to analyze many pieces of DNA. Males with 48, XXXY are diagnosed anywhere from before birth to adulthood as a result of the range in the severity of symptoms. The age range at diagnosis is likely due to the fact that XXXY is a rare syndrome, and does not cause as extreme phenotypes as other variants of Klinefelter syndrome (such as XXXXY).

Diagnostic testing could also be done via blood samples. Elevated levels of follicle stimulating hormone, luteinizing hormone, and low levels of testosterone can be indicative of this syndrome.

It is suggested that the diagnostic criteria for Malpuech syndrome should include cleft lip and/or palate, typical associated facial features, and at least two of the following: urogenital anomalies, caudal appendage, and growth or developmental delay.

Due to the relatively high rate of hearing impairment found with the disorder, it too may be considered in the diagnosis. Another congenital disorder, Wolf-Hirschhorn (Pitt-Rogers-Danks) syndrome, shares Malpuech features in its diagnostic criteria. Because of this lacking differentiation, karyotyping (microscopic analysis of the chromosomes of an individual) can be employed to distinguish the two. Whereas deletions in the short arm of chromosome 4 would be revealed with Wolf-Hirschhorn, a karyotype without this aberration present would favor a Malpuech syndrome diagnosis. Also, the karyotype of an individual with Malpuech syndrome alone will be normal.

Some people may have some mental slowness, but children with this condition often have good social skills. Some males may have problems with fertility.

Diagnosis depends on the clinical scenario. However, karyotyping is an essential test for 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.

Syndactyly and other deformities are typically observed and diagnosed at birth. Long QT syndrome sometimes presents itself as a complication due to surgery to correct syndactyly. Other times, children collapse spontaneously while playing. In all cases it is confirmed with ECG measurements. Sequencing of the CACNA1C gene further confirms the diagnosis.

The diagnosis of Muenke syndrome is suspected bases on abnormal skull shape and a diagnosis of coronal craniosynostosis. In 2006, Agochukwu and her colleagues concluded that “A distinct Muenke syndrome phenotype includes: uni or bilateral coronal synostosis, midface hypoplasia, broad toes, and brachydactyly.” Due to phenotypic overlap and/or mild phenotypes, clinical differentiation of this syndrome may be difficult. The suspected diagnosis is confirmed by a blood test to check for gene mutation. To establish the extent of disease in an individual diagnosed with Muenke syndrome, various evaluations are recommended.

A 'de novo'-situation appears in about 75% of the cases. In 25% of the cases, one of the parents is carrier of the syndrome, without any effect on the parent. Sometimes adults have mild problems with the syndrome. To find out whether either of the parents carries the syndrome, both parents have to be tested. In several cases, the syndrome was identified with the child, because of an autism disorder or another problem, and later it appeared that the parent was affected as well. The parent never knew about it up till the moment that the DNA-test proved the parent to be a carrier.

In families where both parents have been tested negative on the syndrome, chances on a second child with the syndrome are extremely low. If the syndrome was found in the family, chances on a second child with the syndrome are 50%, because the syndrome is autosomal dominant. The effect of the syndrome on the child cannot be predicted.

The syndrome can be detected with fluorescence in situ hybridization and Affymetrix GeneChip Operating Software.

For parents with a child with the syndrome, it is advisable to consult a physician before a next pregnancy and to do prenatal screening.

Turner syndrome may be diagnosed by amniocentesis or chorionic villus sampling during pregnancy.

Usually, fetuses with Turner syndrome can be identified by abnormal ultrasound findings ("i.e.", heart defect, kidney abnormality, cystic hygroma, ascites). In a study of 19 European registries, 67.2% of prenatally diagnosed cases of Turner Syndrome were detected by abnormalities on ultrasound. 69.1% of cases had one anomaly present, and 30.9% had two or more anomalies.

An increased risk of Turner syndrome may also be indicated by abnormal triple or quadruple maternal serum screen. The fetuses diagnosed through positive maternal serum screening are more often found to

have a mosaic karyotype than those diagnosed based on ultrasonographic abnormalities, and

conversely, those with mosaic karyotypes are less likely to have associated ultrasound abnormalities.

According to the Williams Syndrome Association, diagnosis of Williams syndrome begins with recognition of physical symptoms and markers, which is followed by a confirmatory genetic test. The physical signs that often indicate a suspected case of Williams syndrome include puffiness around the eyes, a long philtrum, and a pattern in the iris. Physiological symptoms that often contribute to a Williams syndrome diagnosis are cardiovascular problems, particularly aortic or pulmonary stenosis, as well as feeding disturbance in infants. Developmental delays are often taken as an initial sign of the syndrome, as well.

If a physician suspects a case of Williams syndrome, the diagnosis is confirmed using one of two possible genetic tests: micro-array analysis or the fluorescent in situ hybridization (FISH) test. The FISH test examines chromosome #7 and probes for the existence of two copies of the elastin gene. Since 98-99% of individuals with Williams syndrome lack half of the 7q11.23 region of chromosome #7, where the elastin gene is located, the presence of only one copy of the gene is a strong sign of the syndrome. This confirmatory genetic test has been validated in epidemiological studies of the syndrome, and has been demonstrated to be a more effective method of identifying Williams syndrome than previous methods, which often relied on the presence of cardiovascular problems and facial features (which, while common, are not always present).

Some diagnostic studies suggest that reliance on facial features to identify Williams syndrome may cause a misdiagnosis of the condition. Among the more reliable features suggestive of Williams are congenital heart disease, periorbital fullness ("puffy" eyes), and the presence of a long smooth philtrum. Less reliable signs of the syndrome include anteverted nostrils, a wide mouth, and an elongated neck. Researchers indicate that even with significant clinical experience, it is difficult to reliably identify Williams syndrome based on facial features alone.

The incidence of Fraser syndrome is 0.043 per 10,000 live born infants and 1.1 in 10,000 stillbirths, making it a rare syndrome.

Turner syndrome can be diagnosed postnatally at any age. Often, it is diagnosed at birth due to heart problems, an unusually wide neck or swelling of the hands and feet. However, it is also common for it to go undiagnosed for several years, typically until the girl reaches the age of puberty/adolescence and she fails to develop properly (the changes associated with puberty do not occur). In childhood, a short stature can be indicative of Turner syndrome.

A test called a karyotype, also known as a chromosome analysis, analyzes the chromosomal composition of the individual. This is the test of choice to diagnose Turner syndrome.