Parents of children with Asperger syndrome can typically trace differences in their children's development to as early as 30 months of age. Developmental screening during a routine check-up by a general practitioner or pediatrician may identify signs that warrant further investigation. The United States Preventive Services Task Force in 2016 found it was unclear if screening was beneficial or harmful among children in whom there are no concerns.

The diagnosis of AS is complicated by the use of several different screening instruments, including the Asperger Syndrome Diagnostic Scale (ASDS), Autism Spectrum Screening Questionnaire (ASSQ), Childhood Autism Spectrum Test (CAST) (previously called the Childhood Asperger Syndrome Test), Gilliam Asperger's disorder scale (GADS), Krug Asperger's Disorder Index (KADI), and the Autism-spectrum quotient (AQ; with versions for children, adolescents and adults). None have been shown to reliably differentiate between AS and other ASDs.

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.

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 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.

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.

The 10th revision of the International Statistical Classification of Diseases and Related Health Problems (ICD) classifies the below syndromes as culture-specific 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.

Many children with AS are initially misdiagnosed with attention deficit hyperactivity disorder (ADHD). Diagnosing adults is more challenging, as standard diagnostic criteria are designed for children and the expression of AS changes with age. Adult diagnosis requires painstaking clinical examination and thorough medical history gained from both the individual and other people who know the person, focusing on childhood behavior.

Conditions that must be considered in a differential diagnosis along with ADHD include other ASDs, the schizophrenia spectrum, personality disorders, obsessive–compulsive disorder, major depressive disorder, semantic pragmatic disorder, nonverbal learning disorder, social anxiety disorder, Tourette syndrome, stereotypic movement disorder, bipolar disorder, social-cognitive deficits due to brain damage from alcohol abuse, and obsessive–compulsive personality disorder (OCPD).

In medicine and medical anthropology, a culture-bound syndrome, culture-specific syndrome, or folk illness is a combination of psychiatric and somatic symptoms that are considered to be a recognizable disease only within a specific society or culture. There are no objective biochemical or structural alterations of body organs or functions, and the disease is not recognized in other cultures. The term "culture-bound syndrome" was included in the fourth version of the "Diagnostic and Statistical Manual of Mental Disorders" (American Psychiatric Association, 1994) which also includes a list of the most common culture-bound conditions (DSM-IV: Appendix I). Counterpart within the framework of ICD-10 () are the "culture-specific disorders" defined in Annex 2 of the "Diagnostic criteria for research".

More broadly, an epidemic that can be attributed to cultural behavior patterns or suggestion is sometimes referred to as a behavioral epidemic. As in the cases of drug or alcohol abuse or smoking, transmission can be determined by communal reinforcement as well as by person-to-person interactions. On etiological grounds, it can be difficult to distinguish the causal contribution of culture in disease from other environmental factors such as toxicity.

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.

Some treatments for internalizing disorders include antidepressants, electroconvulsive therapy, and psychotherapy.

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.

Functional somatic syndromes may occur in 6 to 36% of the population.

Treatment may involve investigation, reassurance and explanation, and possibly specialist treatment such as antidepressants or cognitive behavioral therapy.

According to the Williams Syndrome Association, diagnosis of Williams syndrome begins with recognition of physical symptoms and markers, which is followed by a confirmatory genetic test. The physical signs that often indicate a suspected case of Williams syndrome include puffiness around the eyes, a long philtrum, and a pattern in the iris. Physiological symptoms that often contribute to a Williams syndrome diagnosis are cardiovascular problems, particularly aortic or pulmonary stenosis, as well as feeding disturbance in infants. Developmental delays are often taken as an initial sign of the syndrome, as well.

If a physician suspects a case of Williams syndrome, the diagnosis is confirmed using one of two possible genetic tests: micro-array analysis or the fluorescent in situ hybridization (FISH) test. The FISH test examines chromosome #7 and probes for the existence of two copies of the elastin gene. Since 98-99% of individuals with Williams syndrome lack half of the 7q11.23 region of chromosome #7, where the elastin gene is located, the presence of only one copy of the gene is a strong sign of the syndrome. This confirmatory genetic test has been validated in epidemiological studies of the syndrome, and has been demonstrated to be a more effective method of identifying Williams syndrome than previous methods, which often relied on the presence of cardiovascular problems and facial features (which, while common, are not always present).

Some diagnostic studies suggest that reliance on facial features to identify Williams syndrome may cause a misdiagnosis of the condition. Among the more reliable features suggestive of Williams are congenital heart disease, periorbital fullness ("puffy" eyes), and the presence of a long smooth philtrum. Less reliable signs of the syndrome include anteverted nostrils, a wide mouth, and an elongated neck. Researchers indicate that even with significant clinical experience, it is difficult to reliably identify Williams syndrome based on facial features alone.

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.

People with Geschwind syndrome reported higher rates of atypical or altered sexuality. In approximately half of affected individuals hyposexuality is reported. Less commonly, cases of hypersexuality have been reported.

An internalizing disorder is one type of emotional and behavioral disorder, along with externalizing disorders, and low incidence disorders. One who suffers from an internalizing disorder will keep their problems to themselves, or internalize the problems.

Glucocorticoid medications have been known to be associated with significant side effects involving behavior and mood, regardless of previous psychiatric or cognitive condition, since the early 1950s. But cognitive side effects of steroid medications involving memory and attention are not as widely publicized and may be misdiagnosed as separate conditions, such as attention deficit disorder (ADHD or ADD) in children or early Alzheimer's disease in elderly patients.

There has been controversy over the creation of a separate category in the DSM-5 for excoriation (skin picking) disorder. Two of the main reasons for objecting to the inclusion of excoriation disorder in the DSM-5 are: (1) that excoriation disorder may just be a symptom of a different underlying disorder, e.g. OCD or BDD, and (2) that excoriation disorder is merely a bad habit and that by allowing this disorder to obtain its own separate category it would force the DSM to include a wide array of bad habits as separate syndromes, e.g., nail biting and nose-picking. Stein has argued that excoriation disorder does qualify as a separate syndrome and should be classified as its own category because: (1) excoriation disorder occurs as the primary disorder and not as a subset of a larger disorder; (2) excoriation disorder has well-defined clinical features; (3) there is gathering data on the clinical features and diagnostic criteria for this condition; (4) there is sufficient data to create this as a separate category for excoriation disorder; (5) the incidence rate for excoriation disorder is high within the population; (6) diagnostic criteria for the disease have already been proposed; (7) the classification of excoriation disorder as a separate condition would lead to better studies and better treatment outcomes; and (8) classification as a separate condition would lead to more awareness of the disorder and encourage more people to obtain treatment.

Because excoriation disorder is different from other conditions and disorders that cause picking of the skin, it is important that any diagnosis of excoriation disorder take into account various other medical conditions as possible causes before diagnosing the patient with excoriation disorder. There are a variety of conditions that cause itching and skin picking including: eczema, psoriasis, diabetes, liver disease, Hodgkin's disease, polycythemia vera, systemic lupus, and Prader-Willi syndrome.

In order to better understand excoriation disorder, researchers have developed a variety of scales to categorize skin-picking behavior. These include the Skin-Picking Impact Scale (SPIS), and The Milwaukee Inventory for the Dimensions of Adult Skin-picking. The SPIS was created to measure how skin picking affects the individual socially, behaviorally, and emotionally.

As of the release of the fifth Diagnostic and Statistical Manual of Mental Disorders in May 2013, this disorder is classified as its own separate condition under "Obsessive Compulsive and Related Disorders" and is termed "excoriation (skin-picking) disorder".

Definitive diagnosis of FTDP-17 requires a combination of characteristic clinical and pathological features and molecular genetic analysis. Genetic counseling should be offered to affected and at-risk individuals; for most subtypes, penetrance is incomplete.

The term dysphrenia was coined by the German medical specialist Karl Kahlbaum to designate a clinical picture in 19th-century psychiatry. Today the concept is still used in the western world as a lay generic synonym for mental disorder in adults, and as a term to describe different cognitive/verbal/behavioral deficits in children and adolescents. It is also used in the People's Republic of China, controversially, to identify a local medical diagnostic category. A number of followers of the Falun Gong cult and other social movements considered insurrectionary by the regime are said to have been diagnosed with dysphrenia.

The medical expression tardive dysphrenia was first proposed by the American neurologist Stanley Fahn and collaborators in the 1970s. It was originally linked to a unique and rare non-motor behavioral/mental neuroleptic drug-induced tardive syndrome observed in psychiatric patients—schizophrenia in particular—who had been treated with typical antipsychotics.

Tardive dysphrenia was conceived to precede tardive dyskinesia and the other already-known neuroleptic-induced tardive syndromes (tardive dystonia, tardive akathisia). More recently, the Brazilian psychiatrist Leopoldo Hugo Frota extended Fahn's original construct to encompass the independently described but etiologically related concepts of rebound psychosis, supersensitivity psychosis (Guy Chouinard), and schizophrenia pseudo-refractoriness (Heinz Lehmann & Thomas Ban) or secondary acquired refractoriness.

Aside from discontinuation of glucocorticoid medication, potential treatments discussed in the research literature include:

- anti-glucocorticoids

- psychoactive drugs that up-regulate the GRII glucocorticoid receptor:

- tricyclic antidepressants: Desipramine, Imipramine, and Amitriptyline (SSRIs do not )

- serotonin antagonists: Ketanserin

- mood stabilizers: Lithium

- corticotropin-releasing hormone (CRH) antagonists

- glutamate antagonists

- dehydroepiandrosterone (DHEA)

- small molecule brain-derived neurotrophic factor (BDNF) analogs

- stress reduction therapies and exercise.

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.

The prevalence of excoriation disorder is not well understood.

Estimates of prevalence of the condition range from 1.4 to 5.4% in the general population. One U.S. telephone survey found that 16.6% of respondents "picked their skin to the point of noticeable tissue damage" and that 1.4% would qualify as meeting the requirements of excoriation disorder. Another community survey found a rate of 5.4% had excoriation disorder. A survey of college students found a rate of 4%. One study found that among non-disabled adults, 63% of individuals engaged in some form of skin picking and 5.4% engaged in serious skin picking. Lastly, a survey of dermatology patients found that 2% suffered from excoriation disorder.

In some patients excoriation disorder begins with the onset of acne in adolescence, but the compulsion continues even after the acne has gone away. Skin conditions such as keratosis pilaris, psoriasis, and eczema can also provoke the behavior. In patients with acne, the grooming of the skin is disproportionate to the severity of the acne. Certain stressful events including marital conflicts, deaths of friends or family, and unwanted pregnancies have been linked to the onset of the condition. If excoriation disorder does not occur during adolescence another common age of onset is between the ages of 30 to 45. Additionally, many cases of excoriation disorder have been documented to begin in children under the age of 10. One small survey of patients with excoriation disorder found that 47.5% of them had an early onset of excoriation disorder that began before age 10. Traumatic childhood events may initiate the behavior.

Excoriation disorder is statistically more common in females than in males.

Excoriation disorder has a high rate of comorbidity with other psychiatric conditions, especially with mood and anxiety disorders . One survey of patients with excoriation disorder found that 56.7% also had a DSM-IV Axis-I disorder and 38% had alcohol- or drug-abuse problems. Studies have shown the following rates of psychiatric conditions found in patients with excoriation disorder: trichotillomania (38.3%), substance abuse (38%), major depressive disorder (approximately 31.7% to 58.1%), anxiety disorders (approximately 23% to 56%), obsessive-compulsive disorder (approximately 16.7% to 68%), and body dysmorphic disorder (approximately 26.8% to 44.9%). There are also higher rates of excoriation disorder in patients in psychiatric facilities; a study of adolescent psychiatric inpatients found that excoriation disorder was present in 11.8% of patients. It is also present at high rates with some other conditions: 44.9% of patients with body dysmorphic disorder also have excoriation disorder; 8.9% of patients with OCD have excoriation disorder; and 8.3% of patients with trichotillomania have excoriation disorder.

Skin picking is also common in those with certain developmental disabilities; for example, Prader–Willi syndrome and Smith–Magenis syndrome. Studies have shown that 85% of people with Prader–Willi syndrome also engage in skin-picking. Children with developmental disabilities are also at an increased risk for excoriation disorder.

Excoriation disorder also correlates with "social, occupational, and academic impairments, increased medical and mental health concerns (including anxiety, depression, obsessive–compulsive disorder) ... and financial burden". Excoriation disorder also has a high degree of comorbidity with occupational and marital difficulties.

Substance abuse is often present, and individuals with excoriation disorder are twice as likely to have first-degree relatives who have substance abuse disorders than those without the condition.

Some cases of body-focused repetitive behaviors also suggest a hereditary factor.