Most young children do not show any physical signs of FXS. It is not until puberty that physical features of FXS begin to develop. Aside from intellectual disability, prominent characteristics of the syndrome may include an elongated face, large or protruding ears, flat feet, larger testes (macroorchidism), and low muscle tone. Recurrent otitis media (middle ear infection) and sinusitis is common during early childhood. Speech may be cluttered or nervous. Behavioral characteristics may include stereotypic movements (e.g., hand-flapping) and atypical social development, particularly shyness, limited eye contact, memory problems, and difficulty with face encoding. Some individuals with fragile X syndrome also meet the diagnostic criteria for autism.

Males with a full mutation display virtually complete penetrance and will therefore almost always display symptoms of FXS, while females with a full mutation generally display a penetrance of about 50% as a result of having a second, normal X chromosome. Females with FXS may have symptoms ranging from mild to severe, although they are generally less affected than males.

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.

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.

Disorders considered in origin include:

1. Intellectual disability (ID) or intellectual and developmental disability (IDD), previously called mental retardation

2. Autism spectrum disorders, such as Asperger's syndrome or Kanner syndrome

3. Motor disorders including developmental coordination disorder and stereotypic movement disorder Tic disorders including Tourette's syndrome

4. Traumatic brain injury (including congenital injuries such as those that cause cerebral palsy)

5. Communication, speech and language disorders

6. genetic disorders, such as fragile-X syndrome, Down syndrome, attention deficit hyperactivity disorder, schizophrenia, schizotypal disorder, hypogonadotropic hypogonadal syndromes

7. disorders due to neurotoxicants like fetal alcohol spectrum disorder, Minamata disease caused by mercury, behavioral disorders including conduct disorder etc caused by other heavy metals, such as lead, chromium, platinum etc, hydrocarbons like dioxin, PBDEs and PCBs, medications and illegal drugs, like cocaine and others.

Mental retardation and microcephaly with pontine and cerebellar hypoplasia (MICPCH), also known as Mental retardation, X-linked, syndromic, Najm type (MRXSNA), is a rare genetic disorder of infants characterised by intellectual disability and pontocerebellar hypoplasia.

The disorder is associated with a mutation in the "CASK" gene which is transmitted in an X-linked manner. As with the vast majority of genetic disorders, there is no known cure to MICPCH.

The following values seem to be aberrant in children with CASK gene defects: lactate, pyruvate, 2-ketoglutarate, adipic acid and suberic acid, which seems to backup the proposal that CASK affects mitochondrial function. It is also speculated that phosphoinositide 3-kinase in the inositol metabolism is impacted in the disease, causing folic acid metabolization problems.

Neurodevelopmental disorder is a mental disorder. A narrower use of the term refers to a disorder of brain function which affects emotion, learning ability, self-control and memory and which unfolds as the individual grows.

As of 2017 there are 13 types of Ehlers-Danlos syndromes, with a significant overlap in features.

Hypermobile EDS - characterized primarily by joint hypermobility affecting both large and small joints, which may lead to recurrent joint dislocations and subluxations (partial dislocation). In general, people with this type have soft, smooth and velvety skin with easy bruising and chronic pain of the muscles and/or bones.

Classical EDS - associated with extremely elastic (stretchy), smooth skin that is fragile and bruises easily; wide, atrophic scars (flat or depressed scars); and joint hypermobility. Molluscoid pseudotumors (calcified hematomas over pressure points such as the elbow) and spheroids (fat-containing cysts on forearms and shins) are also frequently seen. Hypotonia and delayed motor development may occur.

Vascular EDS - characterized by thin, translucent skin that is extremely fragile and bruises easily. Arteries and certain organs such as the intestines and uterus are also fragile and prone to rupture. People with this type typically have short stature; thin scalp hair; and characteristic facial features including large eyes, a thin nose, and lobeless ears. Joint hypermobility is present, but generally confined to the small joints (fingers, toes). Other common features include club foot; tendon and/or muscle rupture; acrogeria (premature aging of the skin of the hands and feet); early onset varicose veins; pneumothorax (collapse of a lung); recession of the gums; and a decreased amount of fat under the skin.

Kyphoscoliosis EDS - associated with severe hypotonia at birth, delayed motor development, progressive scoliosis (present from birth), and scleral fragility. Affected people may also have easy bruising; fragile arteries that are prone to rupture; unusually small corneas; and osteopenia (low bone density). Other common features include a "marfanoid habitus" which is characterized by long, slender fingers (arachnodactyly); unusually long limbs; and a sunken chest (pectus excavatum) or protruding chest (pectus carinatum).

Arthrochalasia EDS - characterized by severe joint hypermobility and congenital hip dislocation. Other common features include fragile, elastic skin with easy bruising; hypotonia; kyphoscoliosis (kyphosis and scoliosis); and mild osteopenia.

Dermatosparaxis EDS - associated with extremely fragile skin leading to severe bruising and scarring; saggy, redundant skin, especially on the face; and hernias.

Brittle Cornea Syndrome (BCS) characterized by thin cornea, early onset progressive keratoglobus; and blue sclerae.

Classical-like EDS (clEDS) characterized by skin hyperextensibility with velvety skin texture and absence of atrophic scarring, generalized joint hypermobility (GJH) with or without recurrent dislocations (most often shoulder and ankle), and easily bruised skin or spontaneous ecchymoses (discolorations of the skin resulting from bleeding underneath).

Spondylodysplastic EDS (spEDS) characterized by short stature (progressive in childhood), muscle hypotonia (ranging from severe congenital, to mild later-onset), and bowing of limbs.

Musculocontractural EDS (mcEDS) characterized by congenital multiple contractures, characteristically adduction-flexion contractures and/or talipes equinovarus (clubfoot), characteristic craniofacial features, which are evident at birth or in early infancy, and skin features such as skin hyperextensibility, easy bruisability, skin fragility with atrophic scars, increased palmar wrinkling.

Myopathic EDS (mEDS) characterized by congenital muscle hypotonia, and/or muscle atrophy, that improves with age, Proximal joint contractures (joints of the knee, hip and elbow); and hypermobility of distal joints (joints of the ankles, wrists, feet and hands).

Periodontal EDS (pEDS) characterized by severe and intractable periodontitis of early onset (childhood or adolescence), lack of attached gingiva, pretibial plaques; and family history of a first-degree relative who meets clinical criteria.

Cardiac-valvular EDS (cvEDS) characterized by severe progressive cardiac-valvular problems (aortic valve, mitral valve), skin problems (hyperextensibility, atrophic scars, thin skin, easy bruising) and joint hypermobility (generalized or restricted to small joints).

Pregnancies that have a foetus affected with this syndrome are complicated because of polyhydramnion. Complications arise because of opaque amnionic fluid resulting from the shedding of skin. As a result, ultrasounds are difficult to conduct. Triggered by the harsh environment in the uterus, delivery results around 30– 34 weeks of gestation (pregnancy) and the baby is born in prematurely.

The symptoms associated with the disorder are often confused for other dermatological disorders. The symptoms below are ones specifically associated with IPS.

There are several disorders that share some characteristics with Ehlers–Danlos syndrome. For example, in cutis laxa the skin is loose, hanging, and wrinkled. In EDS, the skin can be pulled away from the body but is elastic and returns to normal when let go. In Marfan syndrome, the joints are very mobile and similar cardiovascular complications occur. People with EDS tend to have a "Marfanoid" appearance (e.g., tall, skinny, long arms and legs, "spidery" fingers). However, physical appearance and features in several types of Ehlers–Danlos syndrome also have characteristics including short stature, large eyes, and the appearance of a small mouth and chin, due to a small palate. The palate can have a high arch, causing dental crowding. Blood vessels can sometimes be easily seen through translucent skin, especially on the chest. The genetic connective tissue disorder, Loeys-Dietz Syndrome, also has symptoms that overlap with EDS.

In the past, Menkes disease, a copper metabolism disorder, was thought to be a form of Ehlers–Danlos syndrome. It is not uncommon for patients to be misdiagnosed with fibromyalgia, bleeding disorders or other disorders that can mimic EDS symptoms before a correct diagnosis is made. Because of these similar disorders and complications that can arise from an un-monitored case of EDS, a correct diagnosis is very important. Pseudoxanthoma elasticum (PXE) is worth consideration in diagnosing a patient.

This disorder is characterized by a reduction and loss of subcutaneous fat and collagen of the hands and feet, above all. It can be defined it as a mild, nonprogressive, congenital form of premature skin senility due to the disappearance of the fatty tissue directly under the skin.

More precisely, skin lesions deal with large, fixed, geographic and symmetrical fine scaly recessive erythematous plaques distributed over the dorsal side of distal extremities. Skin lesions can be associated with osteoarticular alterations.

Other outcomes and observations may include abnormally small hands and feet with unusually prominent veins on the upper trunk (chest), short stature, and, sometimes, abnormally small jaw (micrognathia). Most of the cases analyzed show atrophy of the skin at the tip of the nose, which gives a sculptural appearance.The nails may be dystrophic or thick, but, most of the time, they are normal.

In the skin histopathology, there is atrophy of the dermis and subcutaneum. The collagen fibers are loose and dispersed, and the elastic fibers are always fragmented.

However, the epidermis is not affected.

Although some patients present clinical features similar to those of progeria and metageria, they do not usually show generalized atherosclerosis. Therefore, they do not usually have premature myocardic or coronary disease.

Acrogeria (also known as Gottron's syndrome) is a cutaneous condition characterized by premature aging, more especially in the form of unusually fragile, thin skin on the hands and feet (distal extremities). The prefix "acro" stems from the Greek "akros" which alludes to "extremity, tip" while the suffix "geria" comes from the Greek "gerôn" which means "elder".

This is one of the classic congenital premature aging syndromes, occurring early in life, among which are: pangeria (Werner's syndrome), progeria (Hutchinson–Gilford's syndrome) and acrogeria (Gottron's syndrome) and was characterized in 1940. Onset is in early childhood, it progresses over the next few years and then remains stable over time with morphology, colour and site remaining constant. A bruising tendency has been observed.

It is believed that Gottron syndrome may affect more females than males. Approximately forty cases have been reported in the medical literature, since the discovery of the disorder.

The physical symptoms of FXTAS include an intention tremor, cerebellar ataxia, and parkinsonism. This includes small, shuffling steps, muscle rigidity and slowed speech, as well as neuropathic symptoms. As the disease progresses to the more advanced stages, an individual with FXTAS is also at risk of autonomic dysfunction: hypertension, bowel and bladder dysfunction, and impotence.

An individual with FXTAS may also exhibit the following symptoms: a decrease in cognition, which includes diminishing short-term memory and executive function skills, declining math and spelling abilities and decision-making abilities. FXTAS may also result in changes in personality, due to alterations of the limbic area in the brain. This includes increased irritability, angry outbursts, and impulsive behaviour

Among the signs and symptoms of adenylosuccinate lyase deficiency are the following:

- Aggressive behavior

- Microcephaly

- Autism

- Brachycephaly

- Mild Cerebellar hypoplasia

- Seizures

Affected infants present within a few months after birth with failure to thrive and severe folate deficiency manifested as macrocytic anemia and developmental delays. There can be (i) pancytopenia, (ii) diarrhea and/or mucositis and/or (iii) immune deficiency due to T-cell dysfunction and hypoimmunoglobulinemia resulting in pneumonia usually due to Pneumocystis jirovecii. Recently, several infants with the immune deficiency syndrome were described. Untreated, or with inadequate treatment, there are progressive systemic and neurological signs with a spectrum of manifestations including seizures that are often intractable. Females with HFM are fertile and, if folate sufficient during pregnancy, have normal offspring. Subjects that carry one mutated PCFT allele are normal. The genomic and clinical features of HFM were recently reviewed.

Fragile X-associated tremor/ataxia syndrome (FXTAS) is a late-onset neurodegenerative disorder associated with male premutation carriers of Fragile X syndrome (FXS) over the age of 50. The main clinical features of FXTAS include problems of movement with cerebellar gait ataxia and action tremor. Associated features include parkinsonism, cognitive decline, and dysfunction of the autonomic nervous system. FXTAS is found in Fragile X "premutation" carriers, which is defined as a trinucleotide repeat expansion of 55-200 CGG repeats in the Fragile X mental retardation-1 (FMR1) gene. 4-40 CGG repeats in this gene is considered normal, while individual with >200 repeats have full Fragile X Syndrome.

In contrast to FXS full mutation, which is diagnosed early in childhood, symptoms of FXTAS manifest in individuals over the age of 50. Like FXS, FXTAS is most common and most severe in males due to the mutation's X-linked inheritance pattern. FXTAS has an incidence of 40-45% (male) and 16.1% (female) among FXS premutation carriers over the age of 50.

FMR1 mRNA is found to be elevated in patients with FXTAS in contrast to FXS, where the FMR1 gene is transcriptionally silenced via DNA methylation. In both diseases the FMR1 gene product, Fragile X mental retardation protein (FMRP) is diminished, but in FXTAS this is believed to be mediated by RNA toxicity, while in FXS, FMRP is absent due to transcriptional silencing.

There is no cure for FXTAS, but several of the symptoms can be managed with medication.

A birth defect, also known as congenital disorder, is a condition present at birth regardless of cause. They may result in health problems such as physical disability, intellectual disability, or developmental disability. Severity may vary from mild to severe. They are divided into two main types: structural birth defects in which there is problems with the shape of a body part and functional birth defects in which there is problems with how a body part works. Some birth defects include problems of both types.

Birth defects may result from genetic or chromosomal problems, exposure to certain medications or chemicals, or certain infections during pregnancy. Risk factors include not enough folic acid, drinking alcohol or smoking during pregnancy, poorly controlled diabetes, and a mother over the age of 35 years old. Many are believed to involve a number of factors. Birth defects may be visible at birth or diagnosed by screening tests.

Treatment varies depending on the defect in question. This may include therapy, medication, surgery, or assistive technology. Birth defects affected about 96 million people as of 2015. In the United States they occur in about 3% of newborns. They resulted in about 628,000 deaths in 2015 down from 751,000 in 1990. The types with the greatest numbers of deaths are congenital heart disease (303,000), followed by neural tube defects (65,000).

Much of the language used for describing congenital conditions predates genomic mapping, and structural conditions are often considered separately from other congenital conditions. It is now known that many metabolic conditions may have subtle structural expression, and structural conditions often have genetic links. Still, congenital conditions are often classified in a structural basis, organized when possible by primary organ system affected.

Meronanencephaly is a rare form of anencephaly characterized by malformed cranial bones, a median cranial defect, and a cranial protrusion called area cerebrovasculosa. Area cerebrovasculosa is a section of abnormal, spongy, vascular tissue admixed with glial tissue ranging from simply a membrane to a large mass of connective tissue, hemorrhagic vascular channels, glial nodules, and disorganized choroid plexuses.

This condition exists in a variety of forms, ranging from partial absence of the tail bone regions of the spine to absence of the lower vertebrae, pelvis and parts of the thoracic and/or lumbar areas of the spine. In some cases where only a small part of the spine is absent, there may be no outward sign of the condition. In cases where more substantial areas of the spine are absent, there may be fused, webbed, or smaller lower extremities and paralysis. Bowel and bladder control is usually affected.

Additional symptoms include:

- anencephaly (failure of major sections of the brain to form)

- encephalocele (cranial contents protrudes from the skull)

- cyclopia (the two eye cavities fuse into one)

- agnathia

- cleft palate

- arthrogryposis

- clubfeet

- holoprosencephaly

- spina bifida

- low-set ears

- pulmonary hypoplasia

- omphalocele

- gastroschisis

- cardiovascular disorders

- diaphragmatic hernias

- gastrointestinal atresia

- single umbilical artery

- renal abnormalities

- genu recurvatum

- hydramnios

The presentation may be of alopecia (baldness). Individuals vary in severity of symptoms. Nail deformities may also be present as well as hair follicle keratosis and follicular hyperkeratosis.

Hereditary folate malabsorption (HFM - OMIM #229050) is a rare autosomal recessive disorder caused by loss-of-function mutations in the proton-coupled folate transporter (PCFT) gene, resulting in systemic folate deficiency and impaired delivery of folate to the brain.

D-Bifunctional protein deficiency (officially called 17β-hydroxysteroid dehydrogenase IV deficiency) is an autosomal recessive peroxisomal fatty acid oxidation disorder. Peroxisomal disorders are usually caused by a combination of peroxisomal assembly defects or by deficiencies of specific peroxisomal enzymes. The peroxisome is an organelle in the cell similar to the lysosome that functions to detoxify the cell. Peroxisomes contain many different enzymes, such as catalase, and their main function is to neutralize free radicals and detoxify drugs, such as alcohol. For this reason peroxisomes are ubiquitous in the liver and kidney. D-BP deficiency is the most severe peroxisomal disorder, often resembling Zellweger syndrome.

Characteristics of the disorder include neonatal hypotonia and seizures, occurring mostly within the first month of life, as well as visual and hearing impairment. Other symptoms include severe craniofacial disfiguration, psychomotor delay, and neuronal migration defects. Most onsets of the disorder begin in the gestational weeks of development and most affected individuals die within the first two years of life.