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.

About half of parents of children with ASD notice their child's unusual behaviors by age 18 months, and about four-fifths notice by age 24 months. According to an article, failure to meet any of the following milestones "is an absolute indication to proceed with further evaluations. Delay in referral for such testing may delay early diagnosis and treatment and affect the long-term outcome".

- No babbling by 12 months.

- No gesturing (pointing, waving, etc.) by 12 months.

- No single words by 16 months.

- No two-word (spontaneous, not just echolalic) phrases by 24 months.

- Any loss of any language or social skills, at any age.

The United States Preventive Services Task Force in 2016 found it was unclear if screening was beneficial or harmful among children in whom there is no concerns. The Japanese practice is to screen all children for ASD at 18 and 24 months, using autism-specific formal screening tests. In contrast, in the UK, children whose families or doctors recognize possible signs of autism are screened. It is not known which approach is more effective. Screening tools include the Modified Checklist for Autism in Toddlers (M-CHAT), the Early Screening of Autistic Traits Questionnaire, and the First Year Inventory; initial data on M-CHAT and its predecessor, the Checklist for Autism in Toddlers (CHAT), on children aged 18–30 months suggests that it is best used in a clinical setting and that it has low sensitivity (many false-negatives) but good specificity (few false-positives). It may be more accurate to precede these tests with a broadband screener that does not distinguish ASD from other developmental disorders. Screening tools designed for one culture's norms for behaviors like eye contact may be inappropriate for a different culture. Although genetic screening for autism is generally still impractical, it can be considered in some cases, such as children with neurological symptoms and dysmorphic features.

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.

While infection with rubella during pregnancy causes fewer than 1% of cases of autism, vaccination against rubella can prevent many of those cases.

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.

For many adopted or adults and children in foster care, records or other reliable sources may not be available for review. Reporting alcohol use during pregnancy can also be stigmatizing to birth mothers, especially if alcohol use is ongoing. In these cases, all diagnostic systems use an unknown prenatal alcohol exposure designation. A diagnosis of FAS is still possible with an unknown exposure level if other key features of FASD are present at clinical levels.

Confirmed absence of exposure would apply to planned pregnancies in which no alcohol was used or pregnancies of women who do not use alcohol or report no use during the pregnancy. This designation is relatively rare, as most people presenting for an FASD evaluation are at least "suspected" to have had a prenatal alcohol exposure due to presence of other key features of FASD.

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%.

The first diagnosed case of ASD was published in 1943 by American psychiatrist Leo Kanner. There is a wide range of cases and severity to ASD so it is very hard to detect the first signs of ASD. A diagnosis of ASD can be made accurately before the child is 3 years old, but the diagnosis of ASD is not commonly confirmed until the child is somewhat older. The age of diagnosis can range from 9 months to 14 years, and the mean age is 4 years old in the USA. On average each case of ASD is tested at three different diagnostic centers before confirmed. Early diagnosis of the disorder can diminish familial stress, speed up referral to special educational programs and influence family planning.

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.

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

There is no cure for ASD and proper treatment depends on the case and what is most struggled with. Autism spectrum disorder is like many other disorders where when diagnosed early, can be better treated. Different types of therapy are helpful such as music therapy and physical therapy. Other treatments include auditory training, discrete trial training, facilitated communication, and sensory integration therapy.

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.

Diagnosis of megalencephaly has changed over the years, however, with the development of more advanced equipment, physicians have been able to confirm the disorder with better accuracy. Usually, a physical exam is first performed when characteristics of megalencephaly have appeared. This typically occurs at birth or during early child development. A physician will then take head measurements in order to determine the circumference. This is known as the head circumference. Then a family background will be recorded in order to determine if there has been a history of megalencephaly in the family.

A neurological exam will then be performed using the technology of an MRI machine in order to confirm the diagnosis of megalencephaly. These imaging tests give detailed information regarding brain size, volume asymmetry and other irregular developments linked with MCAP, MPPH and hemimegalencephaly.

There is also a strong correlation of epilepsy and megalencephaly and this can aid doctors in their diagnosis.

If a diagnosis of megalencephaly is confirmed, the child is referred to a specialist who focuses on managing the symptoms and improving lifestyle. Since megalencephaly is usually presented with autism, the goal of treatment is to improve deficiencies associated with autistic causes. Additionally, since each patient has unique symptoms, there is no one specific treatment method and therefore is heavily reliant on symptoms associated with an individual.

Conduct disorder is classified in the fourth edition of "Diagnostic and Statistical Manual of Mental Disorders" (DSM). It is diagnosed based on a prolonged pattern of antisocial behaviour such as serious violation of laws and social norms and rules in people younger than the age of 18. Similar criteria are used in those over the age of 18 for the diagnosis of antisocial personality disorder. No proposed revisions for the main criteria of conduct disorder exist in the "DSM-5"; there is a recommendation by the work group to add an additional specifier for callous and unemotional traits. According to DSM-5 criteria for conduct disorder, there are four categories that could be present in the child's behavior: aggression to people and animals, destruction of property, deceitfulness or theft, and serious violation of rules.

Almost all adolescents who have a substance use disorder have conduct disorder-like traits, but after successful treatment of the substance use disorder, about half of these adolescents no longer display conduct disorder-like symptoms. Therefore, it is important to exclude a substance-induced cause and instead address the substance use disorder prior to making a psychiatric diagnosis of conduct disorder.

Once the patient and family have been educated about the nature, management and treatment of the disorder and a decision has been made to treat, the European ADHD Guidelines group recommends medication rather than behavioral training as the first treatment approach; and the UK's National Institute for Health and Clinical Excellence recommends medication as first line treatment for those with hyperkinesis/severe ADHD, and the provision of group parent-training in all cases of ADHD.

ADHD is diagnosed by an assessment of a person's childhood behavioral and mental development, including ruling out the effects of drugs, medications and other medical or psychiatric problems as explanations for the symptoms. It often takes into account feedback from parents and teachers with most diagnoses begun after a teacher raises concerns. It may be viewed as the extreme end of one or more continuous human traits found in all people. Whether someone responds to medications does not confirm or rule out the diagnosis. As imaging studies of the brain do not give consistent results between individuals, they are only used for research purposes and not diagnosis.

In North America, DSM-5 criteria are used for diagnosis, while European countries usually use the ICD-10. With the DSM-IV criteria a diagnosis of ADHD is more likely than with the ICD-10 criteria. It is classified as neurodevelopmental psychiatric disorder. Additionally, it is classified as a disruptive behavior disorder along with oppositional defiant disorder, conduct disorder, and antisocial personality disorder. A diagnosis does not imply a neurological disorder.

Associated conditions that should be screened for include anxiety, depression, oppositional defiant disorder, conduct disorder, and learning and language disorders. Other conditions that should be considered are other neurodevelopmental disorders, tics, and sleep apnea.

Diagnosis of ADHD using quantitative electroencephalography (QEEG) is an ongoing area of investigation, although the value of QEEG in ADHD is currently unclear. In the United States, the Food and Drug Administration has approved the use of QEEG to evaluate the morbidity of ADHD.

Self-rating scales, such as the ADHD rating scale and the Vanderbilt ADHD diagnostic rating scale are used in the screening and evaluation of ADHD.

The rate in school age children is thought to be about 1.5%, compared with an estimated 5.3% for ADHD.

Although not all people with Tourette's have comorbid conditions, most Tourette's patients presenting for clinical care at specialty referral centers may exhibit symptoms of other conditions along with their motor and phonic tics. Associated conditions include attention-deficit hyperactivity disorder (ADD or ADHD), obsessive–compulsive disorder (OCD), learning disabilities and sleep disorders. Disruptive behaviors, impaired functioning, or cognitive impairment in patients with comorbid Tourette's and ADHD may be accounted for by the comorbid ADHD, highlighting the importance of identifying and treating comorbid conditions. Disruption from tics is commonly overshadowed by comorbid conditions that present greater interference to the child. Tic disorders in the absence of ADHD do not appear to be associated with disruptive behavior or functional impairment, while impairment in school, family, or peer relations is greater in patients who have more comorbid conditions and often determines whether therapy is needed.

Because comorbid conditions such as OCD and ADHD can be more impairing than tics, these conditions are included in an evaluation of patients presenting with tics. "It is critical to note that the comorbid conditions may determine functional status more strongly than the tic disorder," according to Samuel Zinner, MD. The initial assessment of a patient referred for a tic disorder should include a thorough evaluation, including a family history of tics, ADHD, obsessive–compulsive symptoms, and other chronic medical, psychiatric and neurological conditions. Children and adolescents with TS who have learning difficulties are candidates for psychoeducational testing, particularly if the child also has ADHD. Undiagnosed comorbid conditions may result in functional impairment, and it is necessary to identify and treat these conditions to improve functioning. Complications may include depression, sleep problems, social discomfort, self-injury, anxiety, personality disorders, oppositional defiant disorder, and conduct disorders.

Reviews of ADHD biomarkers have noted that platelet monoamine oxidase expression, urinary norepinephrine, urinary MHPG, and urinary phenethylamine levels consistently differ between ADHD individuals and healthy control. These measurements could potentially serve as diagnostic biomarkers for ADHD, but more research is needed to establish their diagnostic utility. Urinary and blood plasma phenethylamine concentrations are lower in ADHD individuals relative to controls and the two most commonly prescribed drugs for ADHD, amphetamine and methylphenidate, increase phenethylamine biosynthesis in treatment-responsive individuals with ADHD. Lower urinary phenethylamine concentrations are also associated with symptoms of inattentiveness in ADHD individuals. Electro encephalogram (EEG)) is not accurate enough to make the diagnosis.

Prior to the discovery of a genetic cause, Rett syndrome had been designated as a pervasive developmental disorder by the "Diagnostic and Statistical Manual of Mental Disorders" (DSM), together with the autism spectrum disorders. Some argued against this conclusive assignment because RTT resembles non-autistic disorders such as fragile X syndrome, tuberous sclerosis, or Down syndrome that also exhibit autistic features.

After research proved the molecular mechanism, in 2013 the DSM-5 removed the syndrome altogether from classification as a mental disorder.

Rett syndrome diagnosis involves close observation of the child's growth and development to observe any abnormalities in regards to developmental milestones. A diagnosis is considered when decreased head growth is observed. Conditions with similar symptoms must first be ruled out.

There is a certain criteria that must be met for the diagnosis. A blood test can rule in or rule out the presence of the MECP2 mutation, however, this mutation is present in other conditions as well.

For a classic diagnosis, all four criteria for ruling in a diagnosis must be met, as well as the two criteria for ruling out a diagnosis. A period of symptom regression followed by recovery or symptom stabilization must also occur. Supportive criteria may also be present, but are not required for diagnosis. For an atypical or variant diagnosis, at least two of the four criteria for ruling in the diagnosis must be met, as well as five of the eleven supportive criteria. A period of symptom regression followed by recovery or symptom stabilization must also occur. Children are often misdiagnosed as having autism, cerebral palsy, or another form of developmental delay. A positive test for the MECP2 mutation is not enough to make a diagnosis.

Ruling in

- Decreased or loss of use of fine motor skills

- Decreased or loss of verbal speech

- Abnormalities during gait

- Repetitive hand movements such as wringing/squeezing or clapping/tapping

Ruling out

- Traumatic brain injury, neurometabolic disease, or severe infection that may better explain symptoms

- Abnormal psychomotor development during the 6 months of life

Supportive criteria

- Breathing disturbances when awake

- Bruxism while awake

- Impaired sleep pattern

- Abnormal muscle tone

- Peripheral vasomotor disturbances

- Scoliosis/kyphosis

- Growth retardation

- Small cold hands and feet

- Inappropriate laughing/screaming spells

- Diminished response to pain

- Intense eye communication (eye pointing)

About 25-40% of youths diagnosed with conduct disorder qualify for a diagnosis of antisocial personality disorder when they reach adulthood. For those that do not develop ASPD, most still exhibit social dysfunction in adult life.

Although not necessary for the diagnosis, individuals with intellectual disability are at higher risk for SMD. It is more common in boys, and can occur at any age.

Education, and a "watch and wait" strategy, are the only treatment needed for many, and the majority of individuals with tics do not seek treatment; treatment of tic disorders is similar to treatment of Tourette syndrome.

Assessments for developmental coordination disorder typically require a developmental history, detailing ages at which significant developmental milestones, such as crawling and walking, occurred. Motor skills screening includes activities designed to indicate developmental coordination disorder, including balancing, physical sequencing, touch sensitivity, and variations on walking activities.

The American Psychiatric Association has four primary inclusive diagnostic criteria for determining if a child has developmental coordination disorder.

The criteria are as follows:

1. Motor Coordination will be greatly reduced, although the intelligence of the child is normal for the age.

2. The difficulties the child experiences with motor coordination or planning interfere with the child's daily life.

3. The difficulties with coordination are not due to any other medical condition

4. If the child does also experience comorbidities such as mental retardation; motor coordination is still disproportionally affected.

Screening tests which can be used to assess developmental coordination disorder include:-

- Movement Assessment Battery for Children (Movement-ABC – Movement-ABC 2)

- Peabody Developmental Motor Scales- Second Edition (PDMS-2)

- Bruininks-Oseretsky Test of Motor Proficiency (BOTMP-BOT-2)

- Motoriktest für vier- bis sechsjährige Kinder (MOT 4-6)

- Körperkoordinationtest für Kinder (KTK)

- Test of Gross Motor Development, Second Edition (TGMD-2)

- Maastrichtse Motoriek Test (MMT)

- Wechsler Adult Intelligence Scale (WAIS-IV)

- Wechsler Individual Achievement Test (WAIT-II)

- Test of Word Reading Efficiency (TOWRE-2)

- Developmental Coordination Disorder Questionnaire (DCD-Q)

- Children's Self-Perceptions of Adequacy in, and Predilection for Physical Activity (CSAPPA)

Currently there is no single gold standard assessment test.

A baseline motor assessment establishes the starting point for developmental intervention programs. Comparing children to normal rates of development may help to establish areas of significant difficulty.

However, research in the "British Journal of Special Education" has shown that knowledge is severely limited in many who should be trained to recognise and respond to various difficulties, including developmental coordination disorder, dyslexia and deficits in attention, motor control and perception (DAMP). The earlier that difficulties are noted and timely assessments occur, the quicker intervention can begin. A teacher or GP could miss a diagnosis if they are only applying a cursory knowledge.

"Teachers will not be able to recognise or accommodate the child with learning difficulties in class if their knowledge is limited. Similarly GPs will find it difficult to detect and appropriately refer children with learning difficulties."