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.

There is a division among doctors on the use of the term PDD. Many use the term PDD as a short way of saying PDD-NOS. Others use the general category because the term PDD actually refers to a category of disorders and is not a diagnostic label.

PDD is not itself a diagnosis, while PDD-NOS is a diagnosis. To further complicate the issue, PDD-NOS can also be referred to as "atypical personality development", "atypical PDD", or "atypical Autism".

Because of the "NOS", which means "not otherwise specified", it is hard to describe what PDD-NOS is, other than its being an autism spectrum disorder (ASD). Some people diagnosed with PDD-NOS are close to having Asperger syndrome, but do not quite fit. Others have near full-fledged autism, but without some of its symptoms. The psychology field is considering creating several subclasses within PDD-NOS.

The pervasive developmental disorders are:

- Pervasive developmental disorder not otherwise specified (PDD-NOS), which includes atypical autism, and is the most common (47% of diagnoses);

- Autism, the best-known;

- Asperger syndrome (9% of autism diagnoses);

- Rett syndrome; and

- Childhood disintegrative disorder (CDD).

The first three of these disorders are commonly called the autism spectrum disorders; the last two disorders are much rarer, and are sometimes placed in the autism spectrum and sometimes not.

In May 2013, the "Diagnostic and Statistical Manual-Fifth Edition" ("DSM-5") was released, updating the classification for pervasive developmental disorders. The grouping of disorders, including PDD-NOS, Autism, Asperger Syndrome, Rett Syndrome, and CDD, has been removed and replaced with the general term of Autism Spectrum Disorders. The American Psychiatric Association has concluded that using the general diagnosis of ASD supports more accurate diagnoses. The combination of these disorders was also fueled by the standpoint that Autism is characterized by common symptoms and should therefore bear a single diagnostic term. In order to distinguish between the different disorders, the DSM-5 employs severity levels. The severity levels take into account required support, restricted interests and repetitive behaviors, and deficits in social communication.

There are currently no specific medical treatments for callosal disorders, but individuals with ACC and other callosal disorders may benefit from a range of developmental therapies, educational support, and services. It is important to consult with a variety of medical, health, educational, and social work professionals. Such professionals include neurologists, neuropsychologists, occupational therapists, physical therapists, speech and language pathologists, pediatricians, music therapists, geneticists, Social workers, special educators, early childhood intervention specialists, and caregivers for adults.

The presence of porencephalic cysts or cavities can be detected using trans-illumination of the skull of infant patients. Porencephaly is usually diagnosed clinically using the patients and families history, clinical observations, or based on the presence of certain characteristic neurological and physiological features of porencephaly. Advanced medical imaging with computed tomography (CT), magnetic resonance imaging (MRI), or with ultrasonography can be used as a method to exclude other possible neurological disorders. The diagnosis can be made antenatally with ultrasound. Other assessments include memory, speech, or intellect testing to help further determine the exact diagnose of the disorder.

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 diagnosis of lissencephaly is usually made at birth or soon after by ultrasound, computed tomography (CT), or magnetic resonance imaging (MRI). However, these results should be interpreted cautiously since even experienced radiologists can misdiagnose polymicrogyria, a different developmental malformation of the brain, as lissencephaly.

Before birth, complex ultrasounds performed routinely during pregnancy may indicate the presence of cerebral abnormality, but this method of diagnosis should be complemented by other methods, such as genetic studies and NMR, and the examination is not recommended as part of routine ultrasound examinations, unless family medical history or other reasons for suspecting brain malformation are present. The earliest point during gestation when it is possible to observe abnormal development of the brain surface is approximately in week 20, although ultrasound examinations in week 25–30 are more common. Up to this time, the fetal brain normally has a smooth appearance. If lissencephaly is suspected, chorionic villus sampling can test for some lissencephaly variants, but only those with a known genetic mutation.

Signs and symptoms of ACC and other callosal disorders vary greatly among individuals. However, some characteristics common in individuals with callosal disorders include vision impairments, low muscle tone (hypotonia), poor motor coordination, delays in motor milestones such as sitting and walking, low perception of pain, delayed toilet training, and chewing and swallowing difficulties. Laboratory research has demonstrated that individuals with ACC have difficulty transferring more complex information from one hemisphere to the other. They also have been shown to have some cognitive disabilities (difficulty in complex problem solving) and social difficulties (missing subtle social cues), even when their intelligence quotient is normal. Recent research suggests that specific social difficulties may be a result of impaired face processing. The unusual social behavior in childhood is often mistaken for or misdiagnosed as Asperger syndrome or other autism spectrum disorders. Other characteristics sometimes associated with callosal disorders include seizures, spasticity, early feeding difficulties and/or gastric reflux, hearing impairments, abnormal head and facial features, and a mental handicap.

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.

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.

The approach to diagnosing the cause of hypotonia (as with all syndromes in neurology) is first localization. The physician must first determine if the hypotonia is due to muscle, neuromuscular junction, nerve, or central cause. This will narrow the possible causes. If the cause of the hypotonia is found to lie in the brain, then it can be classified as a cerebral palsy. If the cause is localized to the muscles, it can be classified as a muscular dystrophy. If the cause is thought to be in the nerves, it is call hypotonia due to polyneuropathy. Many cases cannot be definitively diagnosed.

Diagnosing a patient includes obtaining family medical history and a physical examination, and may include such additional tests as computerized tomography (CT) scans, magnetic resonance imaging (MRI) scans, electroencephalogram (EEG), blood tests, genetic testing (such as chromosome karyotyping and tests for specific gene abnormalities), spinal taps, electromyography muscle tests, or muscle and nerve biopsy.

Mild or benign hypotonia is often diagnosed by physical and occupational therapists through a series of exercises designed to assess developmental progress, or observation of physical interactions. Since a hypotonic child has difficulty deciphering his spatial location, he may have some recognizable coping mechanisms, such as locking the knees while attempting to walk. A common sign of low-tone infants is a tendency to observe the physical activity of those around them for a long time before attempting to imitate, due to frustration over early failures. Developmental delay can indicate hypotonia.

The spectrum of lissencephaly is only now becoming more defined as neuroimaging and genetics have provided more insights into migration disorders. There are around 20 types of lissencephaly which make up the spectrum. Other causes which have not yet been identified are likely as well.

Different systems for classifying lissencephaly exist. One major distinction is "classic" (type I) vs. "cobblestone" (type II), but some systems add additional forms that fit into neither of these categories.

Some types of lissencephaly are described below (OMIM numbers are included where available):

The term "hypotonia" comes from the Ancient Greek ὑπο- ("hypo-"), "under" and τόνος ("tónos"), from τείνω ("teinō"), "to stretch". Other terms for the condition include:

This is an ill-defined disorder of uncertain nosological validity. The category is included here because of the evidence that children with moderate to severe intellectual disability (IQ below 35) who exhibit major problems in hyperactivity and inattention frequently show stereotyped behaviours; such children tend not to benefit from stimulant drugs (unlike those with an IQ in the normal range) and may exhibit a severe dysphoric reaction (sometimes with psychomotor retardation) when given stimulants; in adolescence the overactivity tends to be replaced by underactivity (a pattern that is not usual in hyperkinetic children with normal intelligence). It is also common for the syndrome to be associated with a variety of developmental delays, either specific or global. The extent to which the behavioural pattern is a function of low IQ or of organic brain damage is not known, neither is it clear whether the disorders in children with mild intellectual disability who show the hyperkinetic syndrome would be better classified here or under F90.- (Hyperkinetic disorders); at present they are included in F90-.

Diagnostic guidelines

Diagnosis depends on the combination of developmentally inappropriate severe overactivity, motor stereotypies, and moderate to severe intellectual disability; all three must be present for the diagnosis. If the diagnostic criteria for F84.0 (childhood autism), F84.1 (atypical autism) or F84.2 (Rett's syndrome) are met, that condition should be diagnosed instead.

Regression in autism spectrum disorders is well documented; attribution of regression to environmental stress factors may result in a delay in diagnosis. The apparent onset of regressive autism is surprising and distressing to parents, who often initially suspect severe hearing loss. A controversy occurred following a fraudulent study linking MMR vaccine to autism, but since then, studies have shown no connection between autism and the MMR vaccine. There are also studies being done to test if certain types of regressive autism have an autoimmune basis.

The tenth revision of the International Statistical Classification of Diseases and Related Health Problems (ICD-10) has four categories of specific developmental disorder: specific developmental disorders of speech and language, specific developmental disorders of scholastic skills, specific developmental disorder of motor function, and mixed specific developmental disorder.

In the third edition of the "Diagnostic and Statistical Manual of Mental Disorders" (DSM-III), SDD was opposed to the pervasive developmental disorders (PDD). There were two factors that were considered:

- The specificity of the impairment: in SDD there is one single domain that is affected, whereas in PDD multiple areas of functioning are affected.

- The nature of the impairment: development in SDD is delayed but not otherwise abnormal, whereas in PDD there are behavioral deviations that are not typical for any developmental stage.

In the fourth edition of the DSM specific developmental disorders are no longer grouped together. Instead they are reclassified as communication disorders, learning disorders, and motor skills disorders.

Loss of language and skills related to social interaction and self-care are serious. The affected children face ongoing disabilities in certain areas and require long term care. Treatment of CDD involves both behavior therapy, environmental therapy and medications.

- Behavior therapy: The main aim of Applied Behavior Analysis (ABA) is to systematically teach the child to relearn language, self-care and social skills. The treatment programs designed in this respect "use a system of rewards to reinforce desirable behaviors and discourage problem behavior." ABA programs may be designed by a board-certified specialist in behavior analysis called a "BCBA" (Board Certified Behavior Analyst), but ABA is also widely used by a number of other health care personnel from different fields like psychologists, speech therapists, physical therapists and occupational therapists with differing levels of expertise. Parents, teachers and caregivers are instructed to use these behavior therapy methods at all times.

- Environmental Therapy: Sensory Enrichment Therapy uses enrichment of the sensory experience to improve symptoms in autism, many of which are common to CDD.

- Medications: There are no medications available to directly treat CDD. Antipsychotic medications are used to treat severe behavior problems like aggressive stance and repetitive behavior patterns. Anticonvulsant medications are used to control seizures.

Regressive autism occurs when a child appears to develop typically but then starts to lose speech and social skills, typically between the ages of 15 and 30 months, and is subsequently diagnosed with autism. Other terms used to describe regression in children with autism are autism with regression, autistic regression, setback-type autism, and acquired autistic syndrome. There is no standard definition for regression, and the prevalence of regression varies depending on the definition used. Some children show a mixture of features, with some early delays and some later losses; and there is evidence of a continuous spectrum of behaviors, rather than a black-and-white distinction, between autism with and without regression. According to the definitions in the DSM-5 the term "regressive autism" can refer to any type of autism spectrum disorder that involves regression, including Childhood Disintegrative Disorder.

Movement and posture limitations are aspects of all CP types and as a result, CP has historically been diagnosed based on parental reporting of developmental motor delays such as failure to sit upright, reach for objects, crawl, stand, or walk at the appropriate age. Diagnosis of ADCP is also based on clinical assessment used in conjunction with milestone reporting. The majority of ADCP assessments now use the Gross Motor Function Classification System (GMFCS) or the International Classification of Functioning, Disability and Health (formerly the International Classification of Impairments Disease, and Handicaps), measures of motor impairment that are effective in assessing severe CP. ADCP is typically characterized by an individual’s inability to control their muscle tone, which is readily assessed via these classification systems.

Magnetic resonance imaging (MRI) is used to detect morphological brain abnormalities associated with ADCP in patients that are either at risk for ADCP or have shown symptoms thereof. The abnormalities chiefly associated with ADCP are lesions that appear in the basal ganglia. The severity of the disease is proportional to the severity and extent of these abnormalities, and is typically greater when additional lesions appear elsewhere in the deep grey matter or white matter. MRI also has the ability to detect brain malformation, periventricular leukomalacia (PVL), and areas affected by hypoxia-ischemia, all of which may play a role in the development of ADCP. The MRI detection rate for ADCP is approximately 54.5%, however this statistic varies depending on the patient’s age and the cause of the disease and has been reported to be significantly higher.

Three dimensional (3D) T1W, Axial, coronal, sagittal imaging is excellent for differentiation between gray matter and white matter acquisition of high-resolution anatomic information.T2W, Axial and coronal imaging for acquisition of high-resolution anatomic information; delineation of cortex, white matter, and gray matter nuclei. Diffusion tensor, axial imaging is used for evaluation of white matter microstructural integrity, identification of white matter tracts. CISS, axial + MPR imaging for evaluation of cerebellar folia, cranial nerves, ventricles, and foramina. Susceptibility weighted axial scan for Identification and characterization of hemorrhage, blood products, calcification, and iron accumulation.

In general, idic(15) occurs de novo but the parents must be karyotyped to make sure it is not inherited, mostly because this will affect the course of genetic counseling given to the family. If the abnormality is found prenatally and one of the parents harbour the marker, the child has a chance of not carrying the mutation. Further tests should however be done to prove the marker has not been rearranged while being inherited. This information is also necessary for counseling of future pregnancies. Each family is unique and should therefore be handled individually.