Symptoms of M2DS include infantile hypotonia and failure to thrive, delayed psychomotor development, impaired speech, abnormal or absent gait, epilepsy, spasticity, gastrointestinal motility problems, recurrent infections, and genitourinary abnormalities. Many of those affected by M2DS also fit diagnostic criteria for autism. M2DS can be associated with syndromic facies, namely an abnormally flat back of the head, underdevelopment of the midface, ear anomalies, deep-set eyes, prominent chin, pointed nose, and a flat nasal bridge.

Several X-linked syndromes include intellectual disability as part of the presentation. These include:

- Coffin–Lowry syndrome

- MASA syndrome

- MECP2 duplication syndrome

- X-linked alpha thalassemia mental retardation syndrome

- mental retardation and microcephaly with pontine and cerebellar hypoplasia

X-linked intellectual disability (previously known as X-linked mental retardation) refers to forms of intellectual disability which are specifically associated with X-linked recessive inheritance.

As with most X-linked disorders, males are more heavily affected than females. Females with one affected X chromosome and one normal X chromosome tend to have milder symptoms.

Unlike many other types of intellectual disability, the genetics of these conditions are relatively well understood. It has been estimated there are ~200 genes involved in this syndrome; of these ~100 have been identified.

X-linked intellectual disability accounts for ~16% of all cases of intellectual disability in males.

Psychopathology and related behavioral abnormalities are typically seen in LFS, and they may be considered in the diagnosis of the disorder. The most common of these in LFS is an autism-like spectrum disorder, and LFS is considered as one of a number of genetic disorders associated with autism. Additional alterations of psychopathology with behavioral manifestations that have been observed in LFS include: psychotic behavior, schizophrenia, hyperactivity and attention-deficit hyperactivity disorder, aggression, oppositional defiant disorder, obsessive compulsive disorder, extreme shyness, learning disability, cognitive impairment, short-term memory deficit, low frustration tolerance, social dysfunction, lack of impulse control, eating disorder and associated malnutrition, attributed to psychogenic loss of appetite; and pyromania.

While psychiatric conditions like these are to be expected with LFS, there have also been cases of the disorder with some preservation of mental and behavioral abilities, such as problem solving, reasoning and normal intelligence.

The psychopathology of LFS usually exhibits schizophrenia. When schizophrenia is diagnosed in an individual known to be affected by intellectual disability, LFS may be considered in the differential diagnosis of schizophrenia, with confirmation of cause through appropriate psychiatric and genetic evaluation methods.

Most children with Allan–Herndon–Dudley syndrome have weak muscle tone (hypotonia) and underdevelopment of many muscles (muscle hypoplasia). As they get older, they usually develop joint deformities called contractures, which restrict the movement of certain joints. Abnormal muscle stiffness (spasticity), muscle weakness, and involuntary movements of the arms and legs also limit mobility. As a result, many people with Allan–Herndon–Dudley syndrome are unable to walk independently and become wheelchair-bound by adulthood.

LFS is clinically distinguished from other X-linked forms of intellectual disability by the accompanying presence of marfanoid habitus. Marfanoid habitus describes a group of physical features common to Marfan syndrome. Including Marfan syndrome and LFS, marfanoid features of this type have also been observed with several other disorders, one of which is multiple endocrine neoplasia type 2.

In LFS, specific features identified as marfanoid include: a long, narrow face; tall, thin stature; long, slender limbs, fingers and toes (not unlike arachnodactyly) with joint hyperextensibility, shortened halluces (the big toes) and long second toes.

The diagnosis of marfanoid habitus in LFS is often delayed because many of the physical features and characteristics associated with it are usually not evident until adolescence.

The combination of muscular hypotonia and fixed dilated pupils in infancy is suspicious of Gillespie syndrome. Early onset partial aniridia, cerebellar ataxia, and mental retardation are hallmark of syndrome. The iris abnormality is specific and seems pathognomonic of Gillespie syndrome. The aniridia consisting of a superior coloboma and inferior iris hypoplasia, foveomacular dysplasia.

Atypical Gillespie syndrome associated with bilateral ptosis, exotropia, correctopia, iris hypoplasia, anterior capsular lens opacities, foveal hypoplasia, retinal vascular tortuosity, and retinal hypopigmentation.

Neurological signs ar nystagmus, mild craniofacial asymmetry, axial hypotonia, developmental delay, and mild mental retardation. Mariën P did not support the prevailing view of a global mental retardation as a cardinal feature of Gillespie syndrome but primarily reflect cerebellar induced neurobehavioral dysfunctions following disruption of the cerebrocerebellar anatomical circuitry that closely resembles the "cerebellar cognitive and affective syndrome" (CeCAS).

Congenital pulmonary stenosis and helix dysplasia can be associated.

MECP2 Duplication Syndrome (M2DS) is a rare disease that is characterized by severe intellectual disability and impaired motor function. It is an X-linked genetic disorder caused by the overexpression of MeCP2 protein.

Allan–Herndon–Dudley syndrome is a rare X-linked inherited disorder of brain development that causes moderate to severe intellectual disability and problems with movement. This condition, which occurs almost exclusively in males, disrupts development from before birth.

Allan–Herndon–Dudley syndrome, which is named eponymously for William Allan, Florence C. Dudley, and C. Nash Herndon, results from a mutation of the thyroid hormone transporter MCT8 (also referred to as SLC16A2). Consecutively, thyroid hormones are unable to enter the nervous system, which depends on thyroid signaling for proper function and development.

There is a wide range of congenital problems associated with kabuki syndrome with large differences between affected individuals. Some of the common problems are heart defects, urinary tract anomalies, hearing loss, hypotonia, recurrent ear infections and postnatal growth deficiency. Other characteristics include skeletal abnormality, joint laxity, short stature, and unusual dermatoglyphic patterns.

In terms of development, mild to moderate intellectual disability is a common feature. Also, children with kabuki syndrome often have distinctive behavioral features. A few have normal intelligence, most of whom have learning difficulties such as struggling with fine motor, speech skills, and memory.

There is no indication that the life expectancy of individuals with kabuki syndrome is shortened. Most medical issues are resolved with medical intervention. The fact that there are relatively few adults known with this syndrome is probably related to its recent discovery in 1980 in Japan and around 1990 in Europe and America.

Males show more serious symptoms than females affected by this disorder.

The symptoms for males are:

1. Profound sensorineural hearing loss i.e, a complete or almost complete loss of hearing caused by abnormalities in the inner ear.

2. Weak muscle tone - Hypotonia.

3. Impaired muscle coordination - Ataxia.

4. Developmental delay.

5. Intellecual disability.

6. Vision loss caused by optic nerve atrophy in early childhood.

7. Peripheral neuropathy.

8. Recurrent infections, especially in the respiratory system.

9. Muscle weakness caused by recurrent infections.

Symptoms for females:

Very rarely seen hearing loss that begins in adulthood (age > 20 years) combined with ataxia and neuropathy. Optic atrophy and retinitis pigmentosa observed in some cases too.

Theoretically, a mutation in any of the may cause disease, but below are some notable ones, with short description of symptoms:

- Adrenoleukodystrophy; leads to progressive brain damage, failure of the adrenal glands and eventually death.

- Alport syndrome; glomerulonephritis, endstage kidney disease, and hearing loss.

- Androgen insensitivity syndrome; variable degrees of undervirilization and/or infertility in XY persons of either gender

- Barth syndrome; metabolism distortion, delayed motor skills, stamina deficiency, hypotonia, chronic fatigue, delayed growth, cardiomyopathy, and compromised immune system.

- Blue cone monochromacy; low vision acuity, color blindness, photophobia, infantile nystagmus.

- Centronuclear myopathy; where cell nuclei are abnormally located in skeletal muscle cells. In CNM the nuclei are located at a position in the center of the cell, instead of their normal location at the periphery.

- Charcot–Marie–Tooth disease (CMTX2-3); disorder of nerves (neuropathy) that is characterized by loss of muscle tissue and touch sensation, predominantly in the feet and legs but also in the hands and arms in the advanced stages of disease.

- Coffin–Lowry syndrome; severe mental retardation sometimes associated with abnormalities of growth, cardiac abnormalities, kyphoscoliosis as well as auditory and visual abnormalities.

- Fabry disease; A lysosomal storage disease causing anhidrosis, fatigue, angiokeratomas, burning extremity pain and ocular involvement.

- Hunter's Syndrome; potentially causing hearing loss, thickening of the heart valves leading to a decline in cardiac function, obstructive airway disease, sleep apnea, and enlargement of the liver and spleen.

- Hypohidrotic ectodermal dysplasia, presenting with hypohidrosis, hypotrichosis, hypodontia

- Kabuki syndrome; multiple congenital anomalies and mental retardation.

- Spinal and bulbar muscular atrophy; muscle cramps and progressive weakness

- Lesch-Nyhan syndrome; neurologic dysfunction, cognitive and behavioral disturbances including self-mutilation, and uric acid overproduction (hyperuricemia)

- Lowe Syndrome; hydrophthalmia, cataracts, intellectual disabilities, aminoaciduria, reduced renal ammonia production and vitamin D-resistant rickets

- Menkes disease; sparse and coarse hair, growth failure, and deterioration of the nervous system

- Nasodigitoacoustic syndrome; mishaped nose, brachydactyly of the distal phalanges, sensorineural deafness

- Nonsyndromic deafness; hearing loss

- Norrie disease; cataracts, leukocoria along with other developmental issues in the eye

- Occipital horn syndrome; deformations in the skeleton

- Ocular albinism; lack of pigmentation in the eye

- Ornithine transcarbamylase deficiency; developmental delay and mental retardation. Progressive liver damage, skin lesions, and brittle hair may also be seen

- Siderius X-linked mental retardation syndrome; cleft lip and palate with mental retardation and facial dysmorphism, caused by mutations in the histone demethylase PHF8

- Simpson-Golabi-Behmel syndrome; coarse faces with protruding jaw and tongue, widened nasal bridge, and upturned nasal tip

- Spinal muscular atrophy caused by UBE1 gene mutation; weakness due to loss of the motor neurons of the spinal cord and brainstem

- Wiskott-Aldrich syndrome; eczema, thrombocytopenia, immune deficiency, and bloody diarrhea

- X-linked Severe Combined Immunodeficiency (SCID); infections, usually causing death in the first years of life

- X-linked sideroblastic anemia; skin paleness, fatigue, dizziness and enlarged spleen and liver.

Symptoms include:

- intellectual disability (more than half of the patients have an IQ below 50)

- microcephaly

- sometimes pancytopenia (low blood counts)

- cryptorchidism

- low birth weight

- dislocations of pelvis and elbow

- unusually large eyes

- low ears

- small chin

The facial appearance of individuals with this syndrome include long eyelids with turning up of the lateral third of the lower eyelid, a broad and depressed nasal tip, large prominent earlobes, and a cleft or high-arched palate.

Other clinical features often include scoliosis, short fifth finger, persistence of fingerpads, and X-ray abnormalities of the vertebrae, hands, and hip joints.

Gillespie syndrome, also called aniridia, cerebellar ataxia and mental deficiency. is a rare genetic disorder. The disorder is characterized by partial aniridia (meaning that part of the iris is missing), ataxia (motor and coordination problems), and, in most cases, intellectual disability. It is heterogeneous, inherited in either an autosomal dominant or autosomal recessive manner. Gillespie syndrome was first described by American ophthalmologist Fredrick Gillespie in 1965.

The most notable features of Wilson-Turner Syndrome are intellectual disability, obesity, hypogonadism, gynecomastia, and distinct facial features. All of the symptoms are chronic. Affected females are known to have less severe signs and symptoms than males. Female carriers of the disorder may have none or mild symptoms.

- Intellectual Disability is the limitation in an individual's mental functioning and skills. Patients of Wilson-Turner Syndrome have mental disability generally ranging from mild to severe, more frequently on the former. This symptom often coincides with delay in speech development and the occurrence of mood swings. Most males were noted to have a quiet and a cheerful disposition. However, individuals who displayed aggression and became easily upset were also seen. Children will display a delay in speech development often combined with excessive drooling and low voice tone. Some of the studied male patients had speech impairment ranging from little or no speech to minor stuttering.

- Obesity is the accumulation of excess fat on the body. Individuals with Wilson-Turner Syndrome are characterized to have truncal obesity, meaning the fat has accumulated in one's middle. Truncal obesity is often related to heart disease, kidney disease, and lowered blood immune system. Truncal obesity in this disorder becomes more apparent around the age of puberty.

- Tapered fingers is when one end of the finger is diminished in thickness, causing the ends of the fingers to appear pointed. This deformity is not debilitating in any particular manner. In addition to tapered fingers, both hands and feet tend to be small. Some males were observed to have pes planus, also known as flat feet.

- Hypogonadism is a condition in which the gonads have a decrease in function. This condition may result from the lack of sex hormone synthesis, such as androgen and estrogen. Hormones produced by the gonads may also decrease. Hypogonadism also influences the onset of other conditions of the Wilson-Turner Syndrome, such as gynecomastia and decreased testes size in males. It can also cause short stature in men and women. In addition to little genital development, pubic and body hair are scant.

- Some of the facial features that are associated with Wilson-Turner Syndrome include small head circumference, high forehead, prominent ears, and nose with a flattened bridge. There have been cases of a moderately high palate. Low muscle tone and subcutaneous swelling in facial tissue has also been noted. Thick eyebrows are also common. However, there has been reported cases where individuals had none of the mentioned facial features, which shows phenotypic abnormalities have possible environmental influences.

- Gynecomastia is a non-cancerous increase in male breast tissue. It is believed that disturbances in the endocrine system leads to an increase in estrogen and androgen hormones lead to the development of gynecomastia. A key feature of gynecomastia is a rubbery or firm glandular subcutaneous chest tissue that is palpated under the areola of the nipple, instead of the soft fatty tissue. There can also be in increase in diameter of the areola asymmetry in the chest tissue. The breast enlargement can occur in one or both side. Similar to truncal obesity, gynecomastia becomes apparent around the age of puberty.

FG syndrome's major clinical features include intellectual disability, usually severe; hyperactive behavior, often with an outgoing personality; severe constipation, with or without structural anomalies in the anus such as imperforate anus; macrocephaly; severe hypotonia; a characteristic facial appearance due to hypotonia, giving a droopy, "open-mouthed" expression, a thin upper lip, a full or pouting lower lip, and partial or complete loss of the corpus callosum. About a third of reported cases of individuals with FG syndrome die in infancy, usually due to respiratory infection; premature death is rare after infancy.

ATR-16 syndrome affects the blood, development, and brain; symptoms vary based on the specific genes deleted on chromosome 16. Because it is so rare, it is difficult to determine the "core" symptoms of the disease. People with ATR-16 have alpha-thalassemia, a blood disorder where there is less normal hemoglobin in the blood than there should be, and the red blood cells are smaller than they should be (microcytic anemia). Affected children have various characteristic physical features, including clubfoot, "locked" little fingers, microcephaly (small head), hypertelorism (widely spaced eyes), broad, prominent nose bridge, downward-slanted palpebral fissures, small ears, retrognathia, and short neck. Children with ATR-16 syndrome also have mild to moderate intellectual disabilities, developmental delays/growth delays, and speech delays. Some children with ATR-16 have seizures, cryptorchidism (undescended testes), or hypospadias.

Alopecia contractures dwarfism mental retardation syndrome or (ACD mental retardation syndrome) is a developmental disorder which causes mainly baldness and dwarfism in combination with intellectual disability; skeletal anomalies, caries and nearsightedness are also typical.

The ACD mental retardation syndrome was first described in 1980 by Albert Schinzel and only few cases have since been identified in the world. At the time Dr. Schinzel made no conclusion of the hereditary pattern of this syndrome but similarities between cases reported by year 2000 seem to suggest autosomal or x-linked recessive inheritance or possibly a dominant mutation caused by mosaicism as causes of this syndrome.

The three most common symptoms of Opitz G/BBB syndrome (both type I & II) are hypertelorism (exceptionally wide-spaced eyes), laryngo-tracheo-esophalgeal defects (including clefts and holes in the palate, larynx, trachea and esophagus) and hypospadias (urinary openings in males not at the tip of the penis) (Meroni, Opitz G/BBB syndrome, 2012). Abnormalities in the larynx, trachea and esophagus can cause significant difficulty breathing and/or swallowing and can result in reoccurring pneumonia and life-threatening situations. Commonly, there may be a gap between the trachea and esophagus, referred to as a laryngeal cleft; which can allow food or fluid to enter the airway and make breathing and eating a difficult task.

Genital abnormalities like a urinary opening under the penis (hypospadias), undescended testes (cryptorchidism), underdeveloped scrotum and a scrotum divided into two lobes (bifid scrotum) can all be commonplace for males with the disease.

Developmental delays of the brain and nervous system are also common in both types I and II of the disease. 50% of people with Opitz G/BBB Syndrome will experience developmental delay and mild intellectual disability. This can impact motor skills, speech and learning capabilities. Some of these instances are likened to autistic spectrum disorders. Close to half of the people with Opitz G/BBB Syndrome also have a cleft lip (hole in the lip opening) and possibly a cleft palate (hole in the roof of the mouth), as well. Less than half of the people diagnosed have heart defects, imperforate anus (obstructed anal opening), and brain defects. Of all the impairments, female carriers of X-linked Type I Opitz G/BBB Syndrome usually only have ocular hypertelorism.

Arts syndrome is a rare metabolic disorder that causes serious neurological problems in males due to a malfunction of the PRPP synthetase 1 enzyme. Arts Syndrome is part of a spectrum of PRPS-1 related disorders with reduced activity of the enzyme that includes Charcot–Marie–Tooth disease and X-linked non-syndromic sensorineural deafness.

Associated with agenesis (loss) of the corpus callosum, intellectual disabilities are common among individuals with FG syndrome. Motor ability is also impaired as a result of having FG syndrome and its effects on the development of neurons. During infancy, problems arise in the gastrointestinal and gastroesophageal systems of the body. The most common gastrointestinal problems include constipation from imperforated anuses and gastroesophageal reflux. Cardiopulmonary defects also contribute to roughly 60% of premature deaths in infants with FG syndrome. Of all of the congenital heart defects septal defects are the most common. After infancy, long term survival has been recorded to individuals surviving beyond the age of 50.

Ophthalmologic problems include strabismus. This requires early identification to avoid amblyopia. Surgery or patching are usually necessary to treat strabismus if diagnosed early. Refractive errors in patients with FXS are also common.

Most of the signs and symptoms of the Joubert syndrome appear very early in infancy with most children showing delays in gross motor milestones. Although other signs and symptoms vary widely from individual to individual, they generally fall under the hallmark of cerebellum involvement or in this case, lack thereof. Consequently, the most common features include ataxia (lack of muscle control), hyperpnea (abnormal breathing patterns), sleep apnea, abnormal eye and tongue movements, and hypotonia in early childhood. Other malformations such as polydactyly (extra fingers and toes), cleft lip or palate, tongue abnormalities, and seizures may also occur. Developmental delays, including cognitive, are always present to some degree.

Those suffering from this syndrome often exhibit specific facial features such as a broad forehead, arched eyebrows, ptosis (droopy eyelids), hypertelorism (widely spaced eyes), low-set ears and a triangle shaped mouth. Additionally, this disease can include a broad range of other abnormalities to other organ systems such as retinal dystrophy, kidney diseases, liver diseases, skeletal deformities and endocrine (hormonal) problems.

The initial affected individual described in 1986 had a complex phenotype, and was later found to have both beta-mannosidosis and Sanfilippo syndrome. People have been described with a wide spectrum of clinical presentations from infants and children with intellectual disability to adults who present with isolated skin findings (angiokeratomas). Most cases are identified in the first year of life with respiratory infections, hearing loss and intellectual disability. Because of its rarity, and non-specific clinical findings, beta-mannosidosis can go undiagnosed until adulthood, where it can present with intellectual disability and behavioral problems, including aggression.