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.

The brain is usually grossly abnormal in outline when someone is diagnosed with Miller–Dieker syndrome. Only a few shallow sulci and shallow Sylvian fissures are seen; this takes on an hourglass or figure-8 appearance on the axial imaging. The thickness and measurement for a person without MDS is 3–4 mm. With MDS, a person's cortex is measured at 12–20 mm.

While no cure for MDS is available yet, many complications associated with this condition can be treated, and a great deal can be done to support or compensate for functional disabilities. Because of the diversity of the symptoms, it can be necessary to see a number of different specialists and undergo various examinations, including:

- Developmental evaluation

- Cardiologists evaluation

- Otolaryngology

- Treatment of seizures

- Urologic evaluation

- Genetic counseling-balanced chromosomal translocation should be excluded in a parents with an affected child are planning another pregnancy, so parents with affected children should visit a genetic counselor.

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.

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 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.

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.

SMS is usually confirmed by blood tests called chromosome (cytogenetic) analysis and utilize a technique called FISH (fluorescent in situ hybridization). The characteristic micro-deletion was sometimes overlooked in a standard FISH test, leading to a number of people with the symptoms of SMS with negative results.

The recent development of the FISH for 17p11.2 deletion test has allowed more accurate detection of this deletion. However, further testing is required for variations of Smith–Magenis syndrome that are caused by a mutation of the "RAI1" gene as opposed to a deletion.

Children with SMS are often given psychiatric diagnoses such as autism, attention deficit/hyperactivity disorder (ADHD), obsessive-compulsive disorder (OCD), attention deficit disorder (ADD) and/or mood disorders.

A clinical diagnosis of SCS can be verified by testing the TWIST1 gene (only gene in which mutations are known to cause SCS) for mutations using DNA analysis, such as sequence analysis, deletion/duplication analysis, and cytogenetics/ FISH analysis. Sequence analysis of exon 1 (TWIST1 coding region) provides a good method for detecting the frequency of mutations in the TWIST1 gene. These mutations include nonsense, missense, splice site mutation, and intragenic deletions/insertions. Deletion/duplication analysis identifies mutations in the TWIST1 gene that are not readily detected by sequence analysis. Common methods include PCR, multiplex ligation-dependent probe amplification (MLPA), and chromosomal microarray (CMA). Cytogenetic/FISH analysis attaches fluorescently labels DNA markers to a denatured chromosome and is then examined under fluorescent lighting, which reveals mutations caused by translocations or inversions involving 7p21. Occasionally, individuals with SCS have a chromosome translocation, inversion, or ring chromosome 7 involving 7p21 resulting in atypical findings, such as, increased developmental delay. Individuals with SCS, typically have normal brain functioning and rarely have mental impairments. For this reason, if an individual has both SCS and mental retardation, then they should have their TWIST1 gene screened more carefully because this is not a normal trait of SCS. Cytogenetic testing and direct gene testing can also be used to study gene/chromosome defects. Cytogenetic testing is the study of chromosomes to detect gains or losses of chromosomes or chromosome segments using fluorescent in situ hybridization (FISH) and/or comparative genomic hybridization (CGH). Direct gene testing uses blood, hair, skin, amniotic fluid, or other tissues in order to find genetic disorders. Direct gene testing can determine whether an individual has SCS by testing the individual's blood for mutations in the TWIST1 gene.

Treatment of cause: Due to the genetic cause, no treatment of the cause is possible.

Treatment of manifestations: routine treatment of ophthalmologic, cardiac, and neurologic findings; speech, occupational, and physical therapies as appropriate; specialized learning programs to meet individual needs; antiepileptic drugs or antipsychotic medications as needed.

Surveillance: routine pediatric care; routine developmental assessments; monitoring of specific identified medical issues.

Techniques used to diagnose this disorder are fluorescence in situ hybridization (FISH) and microarrays. FISH uses fluorescent dyes to visualize sections under a microscope, but some changes are too small to see. Microarray comparative genomic hybridization (array CGH) shows changes in small amounts DNA on chromosomes.

Up until recently, experts frequently disagreed on whether a patient had SCS, Crouzon syndrome, isolated craniosynostosis, or some other disease because the symptoms are so closely related, they literally had no way of differentiating between all of them. However, we now have direct gene testing, which allows for a more definitive diagnosis because it allows them to be differentiated from each other based on which gene is mutated in each condition. The following is a list of conditions commonly confused/misdiagnosed for SCS, some of their symptoms, and which mutated gene each contains:

Prognoses for 3C syndrome vary widely based on the specific constellation of symptoms seen in an individual. Typically, the gravity of the prognosis correlates with the severity of the cardiac abnormalities. For children with less severe cardiac abnormalities, the developmental prognosis depends on the cerebellar abnormalities that are present. Severe cerebellar hypoplasia is associated with growth and speech delays, as well as hypotonia and general growth deficiencies.

Potocki–Shaffer syndrome can be detected through array comparative genomic hybridization (aCGH).

Some symptoms can be managed with drug therapy, surgery and rehabilitation, genetic counselling, and palliative care.

Y chromosome microdeletion is currently diagnosed by extracting DNA from leukocytes in a man's blood sample, mixing it with some of the about 300 known genetic markers for sequence-tagged sites (STS) on the Y chromosome, and then using polymerase chain reaction amplification and gel electrophoresis in order to test whether the DNA sequence corresponding to the selected markers is present in the DNA.

Such procedures can test only the integrity of a tiny part of the overall 23 million base pair long Y chromosome, therefore the sensitivity of such tests depends on the choice and number of markers used. Present diagnostic techniques can only discover certain types of deletions and mutations on a chromosome and give therefore no complete picture of genetic causes of infertility. They can only demonstrate the presence of some defects, but not the absence of any possible genetic defect on the chromosome.

The gold standard test for genetic mutation, namely complete DNA sequencing of a patient's Y chromosome, is still far too expensive for use in epidemiologic research or even clinical diagnostics.

While only a few adults have been reported with 2q37 microdeletion syndrome, it is predicted that this number will rise as various research studies continue to demonstrate that most with the disorder do not have a shortened life span.

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.

The outcome of this disease is dependent on the severity of the cardiac defects. Approximately 1 in 3 children with this diagnosis require shunting for the hydrocephaly that is often a consequence. Some children require extra assistance or therapy for delayed psychomotor and speech development, including hypotonia.

Treatment of Aicardi syndrome primarily involves management of seizures and early/continuing intervention programs for developmental delays.

Additional comorbidities and complications sometimes seen with Aicardi syndrome include porencephalic cysts and hydrocephalus, and gastro-intestinal problems. Treatment for porencephalic cysts and/or hydrocephalus is often via a shunt or endoscopic of the cysts, though some require no treatment. Placement of a feeding tube, fundoplication, and surgeries to correct hernias or other gastrointestinal structural problems are sometimes used to treat gastro-intestinal issues.

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.

On several locations in the world people are studying on the subject of 1q21.1 deletion syndrome. The syndrome was identified for the first time with people with heart abnormalities. The syndrome has later been found with patients with autism and schizophrenia. Research is done on patients with a symptom of the syndrome, to find more patients with the syndrome.

There may be 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.

Statistical research showed that schizophrenia is more common in combination with 1q21.1 deletion syndrome. On the other side, autism is significantly more common with 1q21.1 duplication syndrome. 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 has been proposed that a deletion or 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.

Research on the genes CHD1L and PRKAB2 within lymphoblast cells lead to the conclusion that anomalies appear with the 1q21.1-deletionsyndrome:

- CHD1L is an enzyme which is involved in untangling the chromatides and the DNA repair system. With 1q21.1 deletion syndrome a disturbance occurs, which leads to increased DNA breaks. The role of CHD1L is similar to that of helicase with the Werner syndrome

- PRKAB2 is involved in maintaining the energy level of cells. With 1q21.1-deletion syndrome this function was attenuated.

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.

Aicardi syndrome is typically characterized by the following triad of features - however, one of the "classic" features being missing does not preclude a diagnosis of Aicardi Syndrome, if other supporting features are present.

1. Partial or complete absence of the corpus callosum in the brain (agenesis of the corpus callosum);

2. Eye abnormalities known as "lacunae" of the retina that are quite specific to this disorder; [optic nerve coloboma]]; and

3. The development in infancy of seizures that are called infantile spasms.

Other types of defects of the brain such as microcephaly, polymicrogyria, porencephalic cysts and enlarged cerebral ventricles due to hydrocephalus are also common in Aicardi syndrome.

Microdeletions in the Y chromosome have been found at a much higher rate in infertile men than in fertile controls and the correlation found may still go up as improved genetic testing techniques for the Y chromosome are developed.

Much study has been focused upon the "azoospermia factor locus" (AZF), at Yq11. A specific partial deletion of AZFc called "gr/gr deletion" is significantly associated with male infertility among Caucasians in Europe and the Western Pacific region.

Additional genes associated with spermatogenesis in men and reduced fertility upon Y chromosome deletions include RBM, DAZ, SPGY, and TSPY.

It is traditionally characterized by hypotonia, short stature, hyperphagia, obesity, behavioral issues (specifically OCD-like behaviors), small hands and feet, hypogonadism, and mild intellectual disability. However, with early diagnosis and early treatment (such as with growth hormone therapy), the prognosis for persons with PWS is beginning to change. Like autism, PWS is a spectrum disorder and symptoms can range from mild to severe and may change throughout the person's lifetime. Various organ systems are affected.

Traditionally, Prader–Willi syndrome was diagnosed by clinical presentation. Currently, the syndrome is diagnosed through genetic testing; testing is recommended for newborns with pronounced hypotonia. Early diagnosis of PWS allows for early intervention as well as the early prescription of growth hormone. Daily recombinant growth hormone (GH) injections are indicated for children with PWS. GH supports linear growth and increased muscle mass, and may lessen food preoccupation and weight gain.

The mainstay of diagnosis is genetic testing, specifically DNA-based methylation testing to detect the absence of the paternally contributed Prader–Willi syndrome/Angelman syndrome (PWS/AS) region on chromosome 15q11-q13. Such testing detects over 97% of cases. Methylation-specific testing is important to confirm the diagnosis of PWS in all individuals, but especially those who are too young to manifest sufficient features to make the diagnosis on clinical grounds or in those individuals who have atypical findings.

Prader–Willi syndrome is often misdiagnosed as other syndromes due to many in the medical community's unfamiliarity with PWS. Sometimes it is misdiagnosed as Down syndrome, simply because of the relative frequency of Down syndrome compared to PWS.

Research on the risk for developing schizophrenia in Ashkenazi Jews and other populations showed that 3q29 microdeletion syndrome leads to a significant higher rate of schizophrenia.