Foreign accent syndrome is a rare medical condition in which patients develop speech patterns that are perceived as a foreign accent that is different from their native accent, without having acquired it in the perceived accent's place of origin.

Foreign accent syndrome usually results from a stroke, but can also develop from head trauma, migraines or developmental problems. The condition was first reported in 1907, and between 1941 and 2009 there were 62 recorded cases.

Its symptoms result from distorted articulatory planning and coordination processes and although popular news articles commonly attempt to identify the closest regional accent, speakers suffering from foreign accent syndrome acquire neither a specific foreign accent nor any additional fluency in a foreign language. Despite an unconfirmed news report in 2010 that a Croatian speaker had gained the ability to speak fluent German after emergence from a coma, there has been no verified case where a patient's foreign language skills have improved after a brain injury. There have been a few reported cases of children and siblings picking up the new accent from someone with foreign accent syndrome.

To the untrained ear, those with the syndrome sound as though they speak their native languages with a foreign accent; for example, an American native speaker of English might sound as though he spoke with a south-eastern English accent, or a native English speaker from Britain might speak with a New York American accent. However, researchers at Oxford University have found that certain specific parts of the brain were injured in some foreign accent syndrome cases, indicating that particular parts of the brain control various linguistic functions, and damage could result in altered pitch and/or mispronounced syllables, causing speech patterns to be distorted in a non-specific manner. Contrary to popular beliefs that individuals with FAS exhibit their accent without any effort, these individuals feel as if they are suffering from a speech disorder. More recently, there is mounting evidence that the cerebellum, which controls motor function, may be crucially involved in some cases of foreign accent syndrome, reinforcing the notion that speech pattern alteration is mechanical, and thus non-specific.

The perception of a foreign accent is likely to be a case of pareidolia on the part of the listener. Nick Miller, Professor of Motor Speech Disorders at Newcastle University has explained: "The notion that sufferers speak in a foreign language is something that is in the ear of the listener, rather than the mouth of the speaker. It is simply that the rhythm and pronunciation of speech has changed."

The late British singer George Michael claimed in 2012 that, after waking from a three-week long coma, he temporarily had a West Country accent.

Symptoms of otodental syndrome can and usually appear in early development and progress with age. Although the specific frequency of the symptoms is not known, the duration is recognized to be for life; assuming no treatment has been undergone. The symptoms are variable to each individual, can range greatly in severity and are dependent on gene expression.

More severe symptoms include:

- Globodontia – an abnormal condition that can occur in both primary and secondary tooth development, in which the molars and canines are greatly enlarged. It refers to the enlarged bulbous fused malformed posterior teeth with almost no discernible cusps or grooves. The molars are known to have a rounded globe-like shape. Can attribute to pain.

- Sensorineural hearing loss (SNHL) – also known as nerve related hearing loss, is a form of hearing loss associated with complications within the inner ear.

- Taurodontism – known as a condition in which the body of a tooth is enlarged at the expense of the roots. This results in an enlarged pulp chamber, lack of proper bonding at the cementoenamel junction, and can cause the pulpal floor to be displaced towards the root. Discomfort and pain are usually associated with these characteristics.

- Endodontic-Periodontic lesions – oral lesions that can potentially form into abscesses. May cause further soreness and pain.

Other possible, less severe, symptoms involve:

- Absent premolars – individuals suffering from otodental syndrome will typically lack the ability to develop premolars due to its genetic related affects.

- Ocular coloboma – an existent hole within the eye of the individual. The hole can be present in either the iris, choroid, optic disc, or retina and is acquired during early/prenatal development. Individuals with these symptoms may exhibit sensitivity to light, blurred vision, and/or blind spots; depending on the size of the missing tissue and its location in the eye.

Otodental syndrome, also known as otodental dysplasia, is an exceptionally rare disease that is distinguished by a specific phenotype known as globodontia, that in rare cases can be associated with eye coloboma and high frequency hearing loss. Globodontia is an abnormal condition that can occur in both the primary and secondary dentition, except for the incisors which are normal in shape and size. This is demonstrated by significant enlargement of the canine and molar teeth. The premolars are either reduced in size or are absent. In some cases, the defects affecting the teeth, eye and ear can be either individual or combined. When these conditions are combined with eye coloboma, the condition is also known as oculo-otodental syndrome. The first known case of otodental syndrome was found in Hungary in a mother and her son by Denes and Csiba in 1969. Prevalence is less than 1 out of every 1 million individuals.

The cause of otodental syndrome is considered to be genetic. It is an autosomal dominant inheritance and is variable in its expressivity. Haploinsufficiency in the fibroblast growth factor 3 (FGF3) gene (11q13) has been reported in patients with otodental syndrome and is thought to cause the phenotype. Both males and females are equally affected. Individuals diagnosed with otodental syndrome can be of any age; age is not a relevant factor.

Currently there are no specific genetic treatments for otodental syndrome. Dental and orthodontic management are the recommended course of action.

When structural impairments are not observable or do not exist, neurological impairments are assessed. In the context of FASD, neurological impairments are caused by prenatal alcohol exposure which causes general neurological damage to the central nervous system (CNS), the peripheral nervous system, or the autonomic nervous system. A determination of a neurological problem must be made by a trained physician, and must not be due to a postnatal insult, such as a high fever, concussion, traumatic brain injury, etc.

All four diagnostic systems show virtual agreement on their criteria for CNS damage at the neurological level, and evidence of a CNS neurological impairment due to prenatal alcohol exposure will result in a diagnosis of FAS or pFAS, and functional impairments are highly likely.

Neurological problems are expressed as either hard signs, or diagnosable disorders, such as epilepsy or other seizure disorders, or soft signs. Soft signs are broader, nonspecific neurological impairments, or symptoms, such as impaired fine motor skills, neurosensory hearing loss, poor gait, clumsiness, poor eye-hand coordination. Many soft signs have norm-referenced criteria, while others are determined through clinical judgment. "Clinical judgment" is only as good as the clinician, and soft signs should be assessed by either a pediatric neurologist, a pediatric neuropsychologist, or both.

Hypotelorism is a medical condition in which there is an abnormally decreased distance between two organs or bodily parts, usually pertaining to eyes (orbits), also known as orbital hypotelorism.

Other conditions may commonly co-occur with FAS, stemming from prenatal alcohol exposure. However, these conditions are considered alcohol-related birth defects and not diagnostic criteria for FAS.

- Heart: A heart murmur that frequently disappears by one year of age. Ventricular septal defect most commonly seen, followed by an atrial septal defect.

- Bones: Joint anomalies including abnormal position and function, altered palmar crease patterns, small distal phalanges, and small fifth fingernails.

- Kidneys: Horseshoe, aplastic, dysplastic, or hypoplastic kidneys.

- Eyes: Strabismus, optic nerve hypoplasia (which may cause light sensitivity, decreased visual acuity, or involuntary eye movements).

- Occasional problems: ptosis of the eyelid, microophthalmia, cleft lip with or without a cleft palate, webbed neck, short neck, tetralogy of Fallot, coarctation of the aorta, spina bifida, and hydrocephalus.

It is often a result of fetal alcohol syndrome (FAS) caused by large alcohol intake in the first month of pregnancy.

It can be associated with trisomy 13 which is also known as Patau syndrome, as well as hereditary neuralgic amyotrophy.

It can also be associated with fragile X syndrome and Prader-Willi syndrome.

Metopic synostosis, the early closure of metopic suture during skull development in children, can also cause hypotelorism.

HIV-associated neurocognitive disorders (HAND) are neurological disorders associated with HIV infection and AIDS. HAND may include neurological disorders of various severity. HIV-associated neurocognitive disorders are associated with a metabolic encephalopathy induced by HIV infection and fueled by immune activation of macrophages and microglia. These cells are actively infected with HIV and secrete neurotoxins of both host and viral origin. The essential features of ADC are disabling cognitive impairment accompanied by motor dysfunction, speech problems and behavioral change. Cognitive impairment is characterised by mental slowness, trouble with memory and poor concentration. Motor symptoms include a loss of fine motor control leading to clumsiness, poor balance and tremors. Behavioral changes may include apathy, lethargy and diminished emotional responses and spontaneity. Histopathologically, it is identified by the infiltration of monocytes and macrophages into the central nervous system (CNS), gliosis, pallor of myelin sheaths, abnormalities of dendritic processes and neuronal loss.

ADC typically occurs after years of HIV infection and is associated with low CD4+ T cell levels and high plasma viral loads. It is sometimes seen as the first sign of the onset of AIDS. Prevalence is between 10–24% in Western countries and has only been seen in 1–2% of India-based infections. With the advent of highly active antiretroviral therapy (HAART), the incidence of ADC has declined in developed countries, although its prevalence is increasing. HAART may prevent or delay the onset of ADC in people with HIV infection, and may also improve mental function in people who already have ADC.

Dementia only exists when neurocognitive impairment in the patient is severe enough to interfere markedly with day-to-day function. That is, the patient is typically unable to work and may not be able to take care of him or herself. Before this, the patient is said to have a mild neurocognitive disorder.

All people with ALPS have signs of lymphoproliferation, which makes it the most common clinical manifestation of the disease. The increased proliferation of lymphoid cells can cause the size of lymphoid organs such as the lymph nodes and spleen to increase (lymphadenopathy and splenomegaly, present in respectively over 90% and over 80% of patients). The liver is enlarged (hepatomegaly in 30 - 40% of patients).

Autoimmune disease is the second most common clinical manifestation and one that most often requires treatment. Autoimmune cytopenias: Most common. Can be mild to very severe. Can be intermittent or chronic. These include: Autoimmune hemolytic anemia, Autoimmune neutropenia, Autoimmune thrombocytopenia.

Other signs can affect organ systems similar to systemic lupus erythematosus (least common, affecting <5% of patients) Symptoms of the nervous system include: Autoimmune cerebellar ataxia; Guillain–Barré syndrome; transverse myelitis. Gastrointestinal signs like Autoimmune esophagitis, gastritis, colitis, hepatitis, pancreatitis can be found or (Dermatologic) Urticaria, (Pulmonary) bronchiolitis obliterans, (Renal) Autoimmune glomerulonephritis, nephrotic syndrome.

Another sign are cancers such as Hodgkin and non-Hodgkin lymphomas which appear to be increased, possibly due to Epstein–Barr virus-encoded RNA-positivity. Some carcinomas may occur. Unaffected family members with genetic mutations are also at an increased risk of developing cancer.

The precise symptoms of a primary immunodeficiency depend on the type of defect. Generally, the symptoms and signs that lead to the diagnosis of an immunodeficiency include recurrent or persistent infections or developmental delay as a result of infection. Particular organ problems (e.g. diseases involving the skin, heart, facial development and skeletal system) may be present in certain conditions. Others predispose to autoimmune disease, where the immune system attacks the body's own tissues, or tumours (sometimes specific forms of cancer, such as lymphoma). The nature of the infections, as well as the additional features, may provide clues as to the exact nature of the immune defect.

While the progression of dysfunction is variable, it is regarded as a serious complication and untreated can progress to a fatal outcome. Diagnosis is made by neurologists who carefully rule out alternative diagnoses. This routinely requires a careful neurological examination, brain scans (MRI or CT scan) and a lumbar puncture to evaluate the cerebrospinal fluid. No single test is available to confirm the diagnosis, but the constellation of history, laboratory findings and examination can reliably establish the diagnosis when performed by experienced clinicians. The amount of virus in the brain does not correlate well with the degree of dementia, suggesting that secondary mechanisms are also important in the manifestation of ADC.

Primary immunodeficiencies are disorders in which part of the body's immune system is missing or does not function normally. To be considered a "primary" immunodeficiency, the cause of the immune deficiency must not be secondary in nature (i.e., caused by other disease, drug treatment, or environmental exposure to toxins). Most primary immunodeficiencies are genetic disorders; the majority are diagnosed in children under the age of one, although milder forms may not be recognized until adulthood. While there are over 100 recognized PIDs, most are very rare. About 1 in 500 people in the United States are born with a primary immunodeficiency. Immune deficiencies can result in persistent or recurring infections, autoinflammatory disorders, tumors, and disorders of various organs. There are currently no cures for these conditions; treatment is palliative and consists of managing infections and boosting the immune system.

Clinically, RALD is characterized by splenomegaly, a relatively mild degree of peripheral lymphadenopathy, and autoimmunity. The autoimmune phenotype can present in childhood or adulthood and primarily includes autoimmune hemolytic anemia, ITP, and neutropenia. Some patients have a history of recurrent respiratory tract infections. It is unclear if increased risk for malignancy is part of RALD.

Importantly, however, the clinical and laboratory phenotype resembles juvenile myelomonocytic leukemia. The high fatality rate of this childhood blood cancer puts it in sharp contrast when compared to the relatively benign and chronic course of RALD. Approximately 15-30% of patients diagnosed with JMML have somatic, activating RAS mutations. However, due to the difficulty in distinguishing JMML from RALD, it is possible a subset of patients treated for JMML actually have RALD and could therefore avoid the aggressive JMML treatment. This distinction is under investigation.

RAS-associated autoimmune leukoproliferative disorder (RALD) is a rare genetic disorder of the immune system. RALD is characterized by lymphadenopathy, splenomegaly, autoimmunity, and elevation in granulocytes and monocytes. It shares many features with autoimmune lymphoproliferative syndrome and is caused by somatic mutations in NRAS or KRAS. This was first described by investigators João Oliveira and Michael Lenardo from the National Institutes of Health.

Autoimmune lymphoproliferative syndrome (ALPS), also known as Canale-Smith syndrome, is a form of lymphoproliferative disorder (LPDs). It affects lymphocyte apoptosis. It is a RASopathy.

It is a rare genetic disorder of abnormal lymphocyte survival caused by defective Fas mediated apoptosis. Normally, after infectious insult, the immune system down-regulates by increasing Fas expression on activated B and T lymphocytes and Fas-ligand on activated T lymphocytes. Fas and Fas-ligand interact to trigger the caspase cascade, leading to cell apoptosis. Patients with ALPS have a defect in this apoptotic pathway, leading to chronic non-malignant lymphoproliferation, autoimmune disease, and secondary cancers.

The hallmark symptom of SS is a generalized dryness, typically including dry mouth and keratoconjunctivitis sicca (dry eyes), part of what are known as sicca ("dryness") symptoms. Sicca syndrome also incorporates vaginal dryness and chronic bronchitis. SS may cause skin, nose, and vaginal dryness, and may affect other organs of the body, including the muscles (myositis), kidneys, blood vessels, lungs, liver, biliary system, pancreas, peripheral nervous system (distal axonal neuropathy or small fiber peripheral neuropathy) and brain. Some people have gastrointestinal or esophageal diseases such as GERD, achlorhydria or gastroparesis. Chronic pain with accompanying fatigue and brain fog may also occur.

Skin dryness in some people with SS may be the result of lymphocytic infiltration into skin glands. The symptoms may develop insidiously, with the diagnosis often not considered for several years, because the complaints of sicca may be otherwise attributed to medications, a dry environment, aging, or may be regarded as not of severity warranting the level of investigation necessary to establish the presence of the specific underlying autoimmune disorder.

SS can damage vital organs of the body with symptoms that may plateau or worsen, or go into remission as with other autoimmune diseases. Some people may experience only the mild symptoms of dry eyes and mouth, while others have symptoms of severe disease. Many patients can treat problems symptomatically. Others are forced to cope with blurred vision, constant eye discomfort, recurrent mouth infections, swollen parotid glands, dysphonia (vocal disorders including hoarseness), and difficulty in swallowing and eating. Debilitating fatigue and joint pain can seriously impair quality of life. Some patients can develop renal (kidney) involvement (autoimmune tubulointerstitial nephritis) leading to proteinuria (excess protein in urine), urinary concentrating defect, and distal renal tubular acidosis.

SS is associated with a number of other medical conditions, many of which are autoimmune or rheumatic disorders, such as celiac disease, fibromyalgia, SLE (lupus), autoimmune thyroiditis, multiple sclerosis and spondyloarthropathy, and several malignancies, principally non-Hodgkin lymphoma.

Developmental toxicity is any structural or functional alteration, reversible or irreversible, which interferes with homeostasis, normal growth, differentiation, development or behavior, and which is caused by environmental insult (including drugs, lifestyle factors such as alcohol, diet, and environmental toxic chemicals or physical factors). It is the study of adverse effects on the development of the organism resulting from exposure to toxic agents before conception (either parent), during prenatal development, or post-natally until puberty. The substance that causes developmental toxicity from embryonic stage to birth is called teratogens. The effect of the developmental toxicants depends on the type of substance, dose and duration and time of exposure.

Certain Pathogens are also included since the toxins they secrete are known to cause adverse effects on the development of the organism when the mother or fetus is infected. Developmental toxicology is a science studying adverse developmental outcomes. This term has widely replaced the early term for the study of primarily structural congenital abnormalities, teratology, to enable inclusion of a more diverse spectrum of congenital disorders. Typical factors causing developmental toxicity are radiation, infections (e.g. rubella), maternal metabolic imbalances (e.g. alcoholism, diabetes, folic acid deficiency), drugs (e.g. anticancer drugs, tetracyclines, many hormones, thalidomide), and environmental chemicals (e.g. mercury, lead, dioxins, PBDEs, HBCD, tobacco smoke). The first-trimester exposure is considered the most potential for developmental toxicity.

Once fertilization has taken place, the toxicants in the environment can pass through the mother to the developing embryo or fetus across the placental barrier. The fetus is at greatest risk during the first 14th to 60th day of the pregnancy when the major organs are being formed. However, depending on the type of toxicant and amount of exposure, a fetus can be exposed toxicant at any time during pregnancy. For example, exposure to a particular toxicant at one time in the pregnancy may result in organ damage and at another time in the pregnancy could cause death of the fetus and miscarriage. There are a number of chemicals, biological agents (such as bacteria and viruses), and physical agents (such as radiation) used in a variety of workplaces that are known to cause developmental disorders. Developmental disorders can include a wide range of physical abnormalities, such as bone or organ deformities, or behavioral and learning problems, such as a mental retardation. Exposures to some chemicals during pregnancy can lead to the development of cancer later in the life of the child and are called transgenerational carcinogens. Exposure to toxicants during the second and the third trimester of a pregnancy can lead to slow fetal grown and result in low birth weight.

Neurodegeneration is the progressive loss of structure or function of neurons, including death of neurons. Many neurodegenerative diseases – including amyotrophic lateral sclerosis, Parkinson's, Alzheimer's, and Huntington's – occur as a result of neurodegenerative processes. Such diseases are incurable, resulting in progressive degeneration and/or death of neuron cells. As research progresses, many similarities appear that relate these diseases to one another on a sub-cellular level. Discovering these similarities offers hope for therapeutic advances that could ameliorate many diseases simultaneously. There are many parallels between different neurodegenerative disorders including atypical protein assemblies as well as induced cell death. Neurodegeneration can be found in many different levels of neuronal circuitry ranging from molecular to systemic.

Nearly all people with TEN have oral, eye and genital involvement as well. Painful crusts and erosions may develop on any mucosal surface. The mouth becomes blistered and eroded, making eating difficult and sometimes necessitating feeding through a nasogastric tube through the nose or a gastric tube directly into the stomach. The eyes can become swollen, crusted, and ulcerated, leading to potential blindness. The most common problem with the eyes is severe conjunctivitis.

Initial skin findings include red-purple, dusky, flat spots known as macules that start on the trunk and spread out from there. These skin lesions then transform into large blisters. The affected skin can then become necrotic or sag from the body and peel off in great swaths.

Lymphoproliferative disorders (LPDs) refer to several conditions in which lymphocytes are produced in excessive quantities. They typically occur in people who have a compromised immune system. They are sometimes equated with "immunoproliferative disorders", but technically lymphoproliferative disorders are a subset of immunoproliferative disorders, along with hypergammaglobulinemia and paraproteinemias.

Chronic use of alcohol used to induce sleep can lead to insomnia: frequent moving between sleep stages occurs, with awakenings due to headaches and diaphoresis. Stopping chronic alcohol abuse can also lead to profound disturbances of sleep with vivid dreams. Chronic alcohol abuse is associated with NREM stage 3 and 4 sleep as well as suppression of REM sleep and REM sleep fragmentation. During withdrawal REM sleep is typically exaggerated as part of a rebound effect.

Essential tremors—or, in the case of essential tremors on a background of family history of essential tremors, familial tremors—can be temporarily relieved in up to two-thirds of patients by drinking small amounts of alcohol.

Ethanol is known to activate aminobutyric acid type A (GABAA) and inhibit N-methyl-D-aspartate (NMDA) glutamate receptors, which are both implicated in essential tremor pathology and could underlie the ameliorative effects. Additionally, the effects of ethanol have been studied in different animal essential tremor models. (For more details on this topic, see Essential tremor.)