Traditionally, genetic abnormalities in neurodevelopmental disorders were detected using karyotype analysis, which found 5% of relevant disorders. , chromosomal microarray analysis (CMA) has replaced karyotyping, because of its greater diagnostic yield in about 20% of cases, detecting smaller chromosome abnormalities. It is the first line genomic test.

New descriptions include the term Copy-number variants (CNVs), which are losses or gains of chromosomal regions greater than 1 kb in length. CNVs are mentioned with the chromosomal band(s) they involve and their genome sequence coordinates. CNVs can be nonrecurrent and recurrent.

With CMA costs of testing have increased from 800 US$ to 1500$. Guidelines from the American College of Medical Genetics and Genomics and the American Academy of Pediatrics recommend CMA as standard of care in the US.

Neurodevelopmental disorders are in their multitude associated with widely varying degrees of difficulty, depending on which there are different degrees of mental, emotional, physical, and economic consequences for individuals, and in turn families, groups and society.

ASD can be detected as early as 18 months or even younger in some cases. A reliable diagnosis can usually be made by the age of two years. The diverse expressions of ASD symptoms pose diagnostic challenges to clinicians. Individuals with an ASD may present at various times of development (e.g., toddler, child, or adolescent), and symptom expression may vary over the course of development. Furthermore, clinicians must differentiate among pervasive developmental disorders, and may also consider similar conditions, including intellectual disability not associated with a pervasive developmental disorder, specific language disorders, ADHD, anxiety, and psychotic disorders.

Considering the unique challenges in diagnosing ASD, specific practice parameters for its assessment have been published by the American Academy of Neurology, the American Academy of Child and Adolescent Psychiatry, and a consensus panel with representation from various professional societies. The practice parameters outlined by these societies include an initial screening of children by general practitioners (i.e., "Level 1 screening") and for children who fail the initial screening, a comprehensive diagnostic assessment by experienced clinicians (i.e. "Level 2 evaluation"). Furthermore, it has been suggested that assessments of children with suspected ASD be evaluated within a developmental framework, include multiple informants (e.g., parents and teachers) from diverse contexts (e.g., home and school), and employ a multidisciplinary team of professionals (e.g., clinical psychologists, neuropsychologists, and psychiatrists).

After a child shows initial evidence of ASD tendencies, psychologists administer various psychological assessment tools to assess for ASD. Among these measurements, the Autism Diagnostic Interview-Revised (ADI-R) and the Autism Diagnostic Observation Schedule (ADOS) are considered the "gold standards" for assessing autistic children. The ADI-R is a semi-structured parent interview that probes for symptoms of autism by evaluating a child's current behavior and developmental history. The ADOS is a semistructured interactive evaluation of ASD symptoms that is used to measure social and communication abilities by eliciting several opportunities (or "presses") for spontaneous behaviors (e.g., eye contact) in standardized context. Various other questionnaires (e.g., The Childhood Autism Rating Scale, Autism Treatment Evaluation Checklist) and tests of cognitive functioning (e.g., The Peabody Picture Vocabulary Test) are typically included in an ASD assessment battery.

In the UK, there is some diagnostic use of the Diagnostic Interview for Social and Communication Disorders (DISCO) was which was developed for use at The Centre for Social and Communication Disorders, by Lorna Wing and Judith Gould, as both a clinical and a research instrument for use with children and adults of any age. The DISCO is designed to elicit a picture of the whole person through the story of their development and behaviour. In clinical work, the primary purpose is to facilitate understanding of the pattern over time of the specific skills and impairments that underlie the overt behaviour. If no information is available, the clinician has to obtain as much information as possible concerning the details of current skills and pattern of behaviour of the person. This type of dimensional approach to clinical description is useful for prescribing treatment.

Brain MRI shows vermis atrophy or hypoplasic. Cerebral and cerebellar atrophy with white matter changes in some cases.

The diagnosis of CdLS is primarily a clinical one, based on medical signs that are evident in a medical history, physical examination, and laboratory tests. Since 2006, testing for NIPBL and SMC1A has been available through the University of Chicago. This is best accomplished through a referral to a genetics specialist or clinic.

CdLS is thought to be underdiagnosed and frequently misdiagnosed.

The first English-language IQ test, the Stanford–Binet Intelligence Scales, was adapted from a test battery designed for school placement by Alfred Binet in France. Lewis Terman adapted Binet's test and promoted it as a test measuring "general intelligence." Terman's test was the first widely used mental test to report scores in "intelligence quotient" form ("mental age" divided by chronological age, multiplied by 100). Current tests are scored in "deviation IQ" form, with a performance level by a test-taker two standard deviations below the median score for the test-taker's age group defined as IQ 70. Until the most recent revision of diagnostic standards, an IQ of 70 or below was a primary factor for intellectual disability diagnosis, and IQ scores were used to categorize degrees of intellectual disability.

Since current diagnosis of intellectual disability is not based on IQ scores alone, but must also take into consideration a person's adaptive functioning, the diagnosis is not made rigidly. It encompasses intellectual scores, adaptive functioning scores from an adaptive behavior rating scale based on descriptions of known abilities provided by someone familiar with the person, and also the observations of the assessment examiner who is able to find out directly from the person what he or she can understand, communicate, and such like. IQ assessment must be based on a current test. This enables diagnosis to avoid the pitfall of the Flynn effect, which is a consequence of changes in population IQ test performance changing IQ test norms over time.

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.

Cytogenetic analysis for fragile X syndrome was first available in the late 1970s when diagnosis of the syndrome and carrier status could be determined by culturing cells in a folate deficient medium and then assessing for "fragile sites" (discontinuity of staining in the region of the trinucleotide repeat) on the long arm of the X chromosome. This technique proved unreliable, however, as the fragile site was often seen in less than 40% of an individual's cells. This was not as much of a problem in males, but in female carriers, where the fragile site could generally only be seen in 10% of cells, the mutation often could not be visualised.

Since the 1990s, more sensitive molecular techniques have been used to determine carrier status. The fragile X abnormality is now directly determined by analysis of the number of CGG repeats using polymerase chain reaction (PCR) and methylation status using Southern blot analysis. By determining the number of CGG repeats on the X chromosome, this method allows for more accurate assessment of risk for premutation carriers in terms of their own risk of fragile X associated syndromes, as well as their risk of having affected children. Because this method only tests for expansion of the CGG repeat, individuals with FXS due to missense mutations or deletions involving "FMR1" will not be diagnosed using this test and should therefore undergo sequencing of the FMR1 gene if there is clinical suspicion of FXS.

Prenatal testing with chorionic villus sampling or amniocentesis allows diagnosis of FMR1 mutation while the fetus is in utero and appears to be reliable.

Early diagnosis of fragile X syndrome or carrier status is important for providing early intervention in children or fetuses with the syndrome, and allowing genetic counselling with regards to the potential for a couple's future children to be affected. Most parents notice delays in speech and language skills, difficulties in social and emotional domains as well as sensitivity levels in certain situations with their children.

Adaptive behavior, or adaptive functioning, refers to the skills needed to live independently (or at the minimally acceptable level for age). To assess adaptive behavior, professionals compare the functional abilities of a child to those of other children of similar age. To measure adaptive behavior, professionals use structured interviews, with which they systematically elicit information about persons' functioning in the community from people who know them well. There are many adaptive behavior scales, and accurate assessment of the quality of someone's adaptive behavior requires clinical judgment as well. Certain skills are important to adaptive behavior, such as:

- Daily living skills, such as getting dressed, using the bathroom, and feeding oneself

- Communication skills, such as understanding what is said and being able to answer

- Social skills with peers, family members, spouses, adults, and others

The assessment for Smith-Finemen-Myers syndrome like any other mental retardation includes a detailed family history and physical exam that tests the mentality of the patient. The patient also gets a brain and skeletal imaging though CT scans or x-rays. They also does a chromosome study and certain other genetic biochemical tests to help figure out any other causes for the mental retardation.

The diagnosis of SFMS is based on visible and measurable symptoms. Until 2000, SFMS was not known to be associated with any particular gene. As of 2001, scientists do not yet know if other genes are involved in this rare disease. Generic analysis of the ATRX gene may prove to be helpful in diagnosis of SFMS.

Autism spectrum disorders tend to be highly comorbid with other disorders. Comorbidity may increase with age and may worsen the course of youth with ASDs and make intervention/treatment more difficult. Distinguishing between ASDs and other diagnoses can be challenging, because the traits of ASDs often overlap with symptoms of other disorders, and the characteristics of ASDs make traditional diagnostic procedures difficult.

The most common medical condition occurring in individuals with autism spectrum disorders is seizure disorder or epilepsy, which occurs in 11-39% of individuals with ASD. Tuberous sclerosis, a medical condition in which non-malignant tumors grow in the brain and on other vital organs, occurs in 1-4% of individuals with ASDs.

Intellectual disabilities are some of the most common comorbid disorders with ASDs. Recent estimates suggest that 40-69% of individuals with ASD have some degree of an intellectual disability, more likely to be severe for females. A number of genetic syndromes causing intellectual disability may also be comorbid with ASD, including fragile X syndrome, Down syndrome, Prader-Willi and Angelman syndromes, and Williams syndrome.

Learning disabilities are also highly comorbid in individuals with an ASD. Approximately 25-75% of individuals with an ASD also have some degree of a learning disability.

Various anxiety disorders tend to co-occur with autism spectrum disorders, with overall comorbidity rates of 7-84%. Rates of comorbid depression in individuals with an ASD range from 4–58%. The relationship between ASD and schizophrenia remains a controversial subject under continued investigation, and recent meta-analyses have examined genetic, environmental, infectious, and immune risk factors that may be shared between the two conditions.

Deficits in ASD are often linked to behavior problems, such as difficulties following directions, being cooperative, and doing things on other people's terms. Symptoms similar to those of attention deficit hyperactivity disorder (ADHD) can be part of an ASD diagnosis.

Sensory processing disorder is also comorbid with ASD, with comorbidity rates of 42–88%.

Differential diagnosis includes Angelman syndrome, Mowat–Wilson syndrome and Rett syndrome.

Kabuki syndrome can be diagnosed using whole exome or whole genome sequencing. Some patients who were initially clinically diagnosed with Kabuki syndrome were actually found to have Wiedemann-Steiner syndrome.

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

Arts syndrome should be included in the differential diagnosis of infantile hypotonia and weakness aggravated by recurrent infection with a family history of X-linked inheritance. Sequence analysis of PRPS1, the only gene associated with Arts syndrome, has detected mutations in both kindreds reported to date. Arts syndrome patients were also found to have reduced levels of hypoxanthine levels in urine and uric acid levels in the serum. In vitro, PRS-1 activity was reduced in erythrocytes and fibroblasts.

Sotos syndrome is not a life-threatening disorder and patients may have a normal life expectancy. Developmental delays may improve in the school-age years; however, coordination problems may persist into adulthood, along with any learning disabilities and/or other physical or mental issues.

The use of biochemical testing for the detection of carriers is technically demanding and not often used. Biochemical analyses that have been performed on hair bulbs from at risk women have had a small number of both false positive and false negative outcomes. If only a suspected carrier female is available for mutation testing, it may be appropriate to grow her lymphocytes in 6-thioguanine (a purine analogue), which allows only HGPRT-deficient cells to survive. A mutant frequency of 0.5–5.0 × 10 is found in carrier females, while a non-carrier female has a frequency of 1–20 × 10. This frequency is usually diagnostic by itself.

Molecular genetic testing is the most effective method of testing, as HPRT1 is the only gene known to be associated with LNS. Individuals who display the full Lesch–Nyhan phenotype all have mutations in the HPRT1 gene. Sequence analysis of mRNA is available clinically and can be utilized in order to detect HPRT1 mutations in males affected with Lesch–Nyhan syndrome. Techniques such as RT-PCR, multiplex genomic PCR, and sequence analysis (cDNA and genomic DNA), used for the diagnosis of genetic diseases, are performed on a research basis. If RT-PCR tests result in cDNA showing the absence of an entire exon or exons, then multiplex genomic PCR testing is performed. Multiplex genomic PCR testing amplifies the nine exons of the HPRT1 gene as eight PCR products. If the exon in question is deleted, the corresponding band will be missing from the multiplex PCR. However, if the exon is present, the exon is sequenced to identify the mutation, therefore causing exclusion of the exon from cDNA. If no cDNA is created by RT-PCR, then multiplex PCR is performed on the notion that most or all of the gene is obliterated.

There are no current treatments or cures for the underlying defects of FXS. Management of FXS may include speech therapy, behavioral therapy, sensory integration occupational therapy, special education, or individualised educational plans, and, when necessary, treatment of physical abnormalities. Persons with fragile X syndrome in their family histories are advised to seek genetic counseling to assess the likelihood of having children who are affected, and how severe any impairments may be in affected descendants.

The Cornelia de Lange Syndrome (CdLS) Foundation is a nonprofit, family support organization based in Avon, Connecticut, that exists to ensure early and accurate diagnosis of CdLS, promote research into the causes and manifestations of the syndrome, and help people with a diagnosis of CdLS, and others with similar characteristics, make informed decisions throughout their lives.

13q deletion syndrome can only be definitively diagnosed by genetic analysis, which can be done prenatally or after birth. Increased nuchal translucency in a first-trimester ultrasound may indicate the presence of 13q deletion.

Diagnosis is made by showing a mutation in the TCF4 gene.

Around 50% of those affected show abnormalities on brain imaging. These include hypoplastic corpus callosum with a missing rostrum and posterior part of the splenium with bulbous caudate nuclei bulging towards the frontal horns.

Electroencephalograms show an excess of slow components.

All have low levels of immunoglobulin M (IgM) but features of an immunodeficiency are absent.

The syndrome primarily affects young males. Preliminary studies suggest that prevalence may be 1.8 per 10,000 live male births. 50% of those affected do not live beyond 25 years of age, with deaths attributed to the impaired immune function.

There is no specific treatment for micro syndrome, but there are ways to help the disorders, and illnesses that come with it. Many individuals with Micro Syndrome need permanent assistance from their disorders and inabilities to move and support themselves. Seizures are not uncommon and patients should get therapy to help control them, and many patients also require wheelchairs to move, so an assistant would be needed at all times.

Those with micro syndrome are born appearing normal. At the age of one, mental and physical delays become apparent, along with some limb spasms. By the age of eight micro syndrome has already set in, and the patient will have joint contractures, Ocular Atrophy will become noticeable, the patient will most likely lose ability to walk, speak, and sometimes move at all.

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.

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.