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.

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

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.

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.

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

Studies suggest that persons with PDD-NOS belong to one of three very different subgroups:

- A high-functioning group (around 25 percent) whose symptoms largely overlap with that of Asperger syndrome, but who differ in terms of having a lag in language development and/or mild cognitive impairment. (The criteria for Asperger syndrome excludes a speech delay or a cognitive impairment.)

- A group (around 25 percent) whose symptoms more closely resemble those of autism spectrum disorder, but do not fully meet all its diagnostic signs and symptoms.

- The biggest group (around 50 percent) consists of those who meet all the diagnostic criteria for autism spectrum disorder, but whose stereotypical and repetitive behaviors are noticeably mild.

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%.

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.

Many normed assessments can be used in evaluating skills in the primary academic domains: reading, including word recognition, fluency, and comprehension; mathematics, including computation and problem solving; and written expression, including handwriting, spelling and composition.

The most commonly used comprehensive achievement tests include the Woodcock-Johnson IV (WJ IV), Wechsler Individual Achievement Test II (WIAT II), the Wide Range Achievement Test III (WRAT III), and the Stanford Achievement Test–10th edition. These tests include measures of many academic domains that are reliable in identifying areas of difficulty.

In the reading domain, there are also specialized tests that can be used to obtain details about specific reading deficits. Assessments that measure multiple domains of reading include Gray's Diagnostic Reading Tests–2nd edition (GDRT II) and the Stanford Diagnostic Reading Assessment. Assessments that measure reading subskills include the Gray Oral Reading Test IV – Fourth Edition (GORT IV), Gray Silent Reading Test, Comprehensive Test of Phonological Processing (CTOPP), Tests of Oral Reading and Comprehension Skills (TORCS), Test of Reading Comprehension 3 (TORC-3), Test of Word Reading Efficiency (TOWRE), and the Test of Reading Fluency. A more comprehensive list of reading assessments may be obtained from the Southwest Educational Development Laboratory.

The purpose of assessment is to determine what is needed for intervention, which also requires consideration of contextual variables and whether there are comorbid disorders that must also be identified and treated, such as behavioral issues or language delays. These contextual variables are often assessed using parent and teacher questionnaire forms that rate the students' behaviors and compares them to standardized norms.

However, caution should be made when suspecting the person with a learning disability may also have dementia, especially as people with Down's syndrome may have the neuroanatomical profile but not the associated clinical signs and symptoms. Examination can be carried out of executive functioning as well as social and cognitive abilities but may need adaptation of standardized tests to take account of special needs.

Assessment will usually include an interview with the child’s caregiver, observation of the child in an unstructured setting, a hearing test, and standardized tests of language. There is a wide range of language assessments in English. Some are restricted for use by experts in speech-language pathology: speech and language therapists (SaLTs/SLTs) in the UK, speech-language pathologists (SLPs) in the US and Australia. A commonly used test battery for diagnosis of DLD is the Clinical Evaluation of Language Fundamentals (CELF).

Assessments that can be completed by a parent or teacher can be useful to identify children who may require more in-depth evaluation. The Children’s Communication Checklist (CCC–2) is a parent questionnaire suitable for assessing everyday use of language in children aged 4 years and above who can speak in sentences.

Informal assessments, such as language samples, are often used by speech-language therapists/pathologists to complement formal testing and give an indication of the child's language in a more naturalistic context. A language sample may be of a conversation or narrative retell. In a narrative language sample, an adult may tell the child a story using a wordless picture book (e.g. Frog Where Are You?, Mayer, 1969), then ask the child to use the pictures and tell the story back. Language samples can be transcribed using computer software such as the Systematic Analysis of Language Software, and then analyzed for a range of features: e.g., the grammatical complexity of the child's utterances, whether the child introduces characters to their story or jumps right in, whether the events follow a logical order, and whether the narrative includes a main idea or theme and supporting details.

There are no objectively definitive statistics about how many people have savant skills. The estimates range from "exceedingly rare" to one in ten people with autism having savant skills in varying degrees. A 2009 British study of 137 parents of autistic children found that 28% believe their children met the criteria for a savant skill, defined as a skill or power "at a level that would be unusual even for 'normal' people". As many as 50 cases of sudden or acquired savant syndrome have been reported.

Males with savant syndrome outnumber females by roughly 6:1, slightly higher than the sex ratio disparity for autism spectrum disorders of 4.3:1.

Savant syndrome is a condition in which a person demonstrates one or more profound and prodigious capacities or abilities far in excess of what would be considered normal, yet often also has significant deficits in other areas of brain processing.

People with savant syndrome may have neurodevelopmental disorders, notably autism spectrum disorders (in which case they are often referred to as autistic savants), or brain injuries. The most dramatic examples of savant syndrome occur in individuals who score very low on IQ tests, while demonstrating exceptional skills or brilliance in specific areas, such as rapid calculation (hypercalculia), art, memory, or musical ability. Although termed a syndrome, it is not recognized as a mental disorder nor as part of a mental disorder in medical manuals such as the ICD-10 or the DSM-5.

Another form of savant syndrome is acquired savant syndrome, in which a person acquires prodigious capabilities or skills following dementia, a head injury or concussion, epilepsy, or other brain disturbances. This syndrome is more rare, with a study by Darold Treffert in 2010 showing that in a registry of 319 known savants, only 32 had acquired savant syndrome.

PDD-NOS is an old diagnostic category. It is no longer included as an option for an Autism Spectrum Disorder and is not part of the DSM-5, but is included in the ICD-10.

The diagnosis of a pervasive developmental disorder not otherwise specified is given to individuals with difficulties in the areas of social interaction, communication, and/or stereotyped behavior patterns or interests, but who do not meet the full DSM-IV criteria for autism or another PDD. This does not necessarily mean that PDD-NOS is a milder disability than the other PDDs. It only means that individuals who receive this diagnosis do not meet the diagnostic criteria of the other PDDs, but that there is still a pervasive developmental disorder that affects the individual in the areas of communication, socialization and behavior.

As for the other pervasive developmental disorders, diagnosis of PDD-NOS requires the involvement of a team of specialists. The individual needs to undergo a full diagnostic evaluation, including a thorough medical, social, adaptive, motor skills and communication history. Other parts of an assessment can be behavioral rating scales, direct behavioral observations, psychological assessment, educational assessment, communication assessment, and occupational assessment.

Description of PDD-NOS merely as a "subthreshold" category without a more specific case definition poses methodological problems for research regarding the relatively heterogeneous group of people who receive this diagnosis. However, it appears that children with PDD-NOS show fewer intellectual deficits than autistic children, and that they may come to professional attention at a later age.

Although LFS is usually suspected when intellectual disability and marfanoid habitus are observed together in a patient, the diagnosis of LFS can be confirmed by the presence of the p.N1007S missense mutation in the "MED12" gene.

Late talker is a term used for exceptionally bright people who experience a delay in the development of speech. Commonalities include usually being boys, delayed speech development, highly educated parents, musically gifted families, puzzle-solving abilities, and lagging social development. Many high-achieving late talkers were notoriously strong willed and noncompliant as children. Late talkers can often be misdiagnosed early on as having severe ("low-functioning") autism spectrum disorder (a category known simply as "autism", prior to the DSM-5), and careful professional evaluation is necessary for differential diagnosis, according to Darold Treffert and other experts. One major difference between late talkers and low-functioning autistic children is that for late talkers, communication skills automatically reach a normal level and the child requires no further special treatment with regards to speech. Outlook for late talkers with or without intervention is generally favorable. However, late language emergence can also be an early or secondary sign of high-functioning autism spectrum disorder / Asperger syndrome, or other developmental disorders, such as attention deficit hyperactivity disorder, intellectual disability, learning disability, social communication disorder, or specific language impairment.

Einstein syndrome, a term coined by the economist Thomas Sowell, is also sometimes used to describe late talkers. The term is named after Albert Einstein (often said to have been a late talker, though with questionable evidence), whom Sowell used as the primary example of a late talker in his work. Sowell also included Edward Teller, Srinivasa Ramanujan, the mathematician Julia Robinson, Richard Feynman, and the pianists Clara Schumann and Arthur Rubinstein to be in the late talkers group. As a toddler, the scientist John Clive Ward showed similar behavioral traits to those described by Sowell, according to a brief sketch of his biography.

Sowell claimed late talkers are often inaccurately categorized as having an autism spectrum disorder (ASD), and that a small subset of late talkers are highly intelligent children with common characteristics concentrated in music, memory, math or the sciences. However, as reported by Simon Baron-Cohen, such characteristics are often found in high-functioning autism / Asperger syndrome.

Intellectual disability in children can be caused by genetic or environmental factors. The individual could have a natural brain malformation or pre or postnatal damage done to the brain caused by drowning or a traumatic brain injury, for example. Nearly 30 to 50% of individuals with intellectual disability will never know the cause of their diagnosis even after thorough investigation.

Prenatal causes of intellectual disability include:

- Congenital infections such as cytomegalovirus, toxoplasmosis, herpes, syphilis, rubella and human immunodeficiency virus

- Prolonged maternal fever in the first trimester

- Exposure to anticonvulsants or alcohol

- Untreated maternal phenylketonuria (PKU)

- Complications of prematurity, especially in extremely low-birth-weight infants

- Postnatal exposure to lead

Single-gene disorders that result in intellectual disability include:

- Fragile X syndrome

- Neurofibromatosis

- Tuberous sclerosis

- Noonan's syndrome

- Cornelia de Lange's syndrome

These single-gene disorders are usually associated with atypical physical characteristics.

About 1/4 of individuals with intellectual disability have a detectable chromosomal abnormality. Others may have small amounts of deletion or duplication of chromosomes, which may go unnoticed and therefore, undetermined.

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.

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.

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

In the differential diagnosis of LFS, another disorder that exhibits some features and symptoms of LFS and is also associated with a missense mutation of "MED12" is Opitz-Kaveggia syndrome (FGS). Common features shared by both LFS and FGS include X-linked intellectual disability, hyperactivity, macrocephaly, corpus callosum agenesis and hypotonia. Notable features of FGS that have not been reported with LFS include excessive talkativness, consistent strength in socialization skills, imperforate anus (occlusion of the anus) and ocular hypertelorism (extremely wide-set eyes).

Whereas LFS is associated with missense mutation p.N1007S, FGS is associated with missense mutation p.R961W. As both disorders originate from an identical type of mutation in the same gene, while exhibiting similar, yet distinct characteristics; LFS and FGS are considered to be allelic. In the context of "MED12", this suggests that the phenotype of each disorder is related to the way in which their respective mutations alter the "MED12" sequence and its function.

Borderline intellectual functioning, also called borderline mental disability, is a categorization of intelligence wherein a person has below average cognitive ability (generally an IQ of 70–85), but the deficit is not as severe as intellectual disability (below 70). It is sometimes called below average IQ (BAIQ). This is technically a cognitive impairment; however, this group may not be sufficiently mentally disabled to be eligible for specialized services. The DSM-IV-TR codes borderline intellectual functioning as V62.89.

During school years, individuals with borderline intellectual functioning are often "slow learners." Although a large percentage of this group fails to complete high school and can often achieve only a low socioeconomic status, most adults in this group blend in with the rest of the population.

The prognosis for individuals with schizencephaly varies depending on the size of the clefts and the degree of neurological deficit.