Bloom syndrome is characterized by genome instability. The most prominent features include short stature and a rash on the face that develops early in life when exposed to the sun. The skin rash is erythematous, telangiectatic, infiltrated, and scaly, it can appear across the nose, on the cheeks and around the lips. As well as these areas the rash will develop on any other sun-exposed areas including, the backs of the hands and neck. Other clinical features include a high-pitched voice; distinct facial features, including a long, narrow face, micrognathism, and prominent nose and ears; pigmentation changes of the skin including hypo-pigmented and hyper-pigmented areas, cafe-au-lait spots, and telangiectasias (dilated blood vessels), which can appear on the skin and eyes. Moderate immune deficiency, characterized by deficiency in certain immunoglobulin classes has also been related to BS, leading to recurrent pneumonia and ear infections. Most individuals with Bloom syndrome are born with a low birth weight. Hypogonadism is characterized by a failure to produce sperm, hence infertility in males, and premature cessation of menses (premature menopause), hence sub-fertility in females. However, several women with Bloom syndrome have had children. The most serious and common complication of Bloom syndrome is cancer. Other complications of the disorder include chronic obstructive lung disease, diabetes, and learning disabilities. There is no evidence that mental retardation is more common in Bloom syndrome than in other people. People with Bloom Syndrome have a shortened life expectancy; the average life span is approximately 27 years. Bloom syndrome shares some features with Fanconi anemia possibly because there is overlap in the function of the proteins mutated in this related disorder.

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 symptoms of ichthyosis hystrix Curth-Macklin are similar to epidermolytic hyperkeratosis (NPS-2 type) but there is no blistering and the hyperkeratosis is verrucous or spine-like. The hyperkeratosis is brown-grey in colour and is most obvious on the arms and legs. It is an autosomal dominant condition and can be caused by errors to the KRT1 gene. It is named after Helen Ollendorff Curth (1899-1982), a German-Jewish dermatologist, and Madge Thurlow Macklin (1893–1962), an American medical geneticist, and is one of the first syndromes named after two women.

Ichthyosis hystrix is a group of rare skin disorders in the ichthyosis family of skin disorders characterized by massive hyperkeratosis with an appearance like spiny scales. This term is also used to refer to a type of epidermal nevi with extensive bilateral distribution.

There are three main disorders caused by Hermansky–Pudlak syndrome, which result in these symptoms:

- Albinism and eye problems: Individuals will have varying amounts of skin pigment (melanin). Because of the albinism there are eye problems such as light sensitivity (photophobia), strabismus (crossed eyes), and nystagmus (involuntary eye movements). Hermansky–Pudlak syndrome also impairs vision.

- Bleeding disorders: Individuals with the syndrome have platelet dysfunction. Since platelets are necessary for blood clotting, individuals will bruise and bleed easily.

- Cellular storage disorders: The syndrome causes a wax-like substance (ceroid) to accumulate in the body tissues and cause damage, especially in the lungs and kidneys.

It is also associated with granulomatous colitis, an inflammation of the colon, and with pulmonary fibrosis, a potentially fatal lung disease.

Bloom syndrome (often abbreviated as BS in literature), also known as Bloom-Torre-Machacek syndrome, is a rare autosomal recessive disorder characterized by short stature, predisposition to the development of cancer and genomic instability. BS is caused by mutations in the BLM gene leading to mutated DNA helicase protein formation. Cells from a person with Bloom syndrome exhibit a striking genomic instability that includes excessive crossovers between homologous chromosomes and sister chromatid exchanges (SCEs). The condition was discovered and first described by New York dermatologist Dr. David Bloom in 1954.

Joubert syndrome is a rare autosomal recessive genetic disorder that affects the cerebellum, an area of the brain that controls balance and coordination.

Joubert syndrome is one of the many genetic syndromes associated with syndromic retinitis pigmentosa. The syndrome was first identified in 1969 by pediatric neurologist Marie Joubert in Montreal, Quebec, Canada, while working at the Montreal Neurological Institute and McGill University.

The characteristic symptom of Costeff syndrome is the onset of progressively worsening eyesight caused by degeneration of the optic nerve (optic atrophy) within the first few years of childhood, with the majority of affected individuals also developing motor disabilities later in childhood. Occasionally, people with Costeff syndrome may also experience mild cognitive disability.

It is type of 3-methylglutaconic aciduria, the hallmark of which is an increased level in the urinary concentrations of 3-methylglutaconic acid and 3-methylglutaric acid; this can allow diagnosis as early as at one year of age.

Those with Costeff syndrome typically experience the first symptoms of visual deterioration within the first few years of childhood, which manifests as the onset of progressively decreasing visual acuity. This decrease tends to continue with age, even after childhood.

The majority of people with Costeff syndrome develop movement problems and motor disabilities later in childhood, the two most significant of which are choreoathetosis and spasticity. The former causes involuntary erratic, jerky, and twisting movements (see chorea and athetosis), whereas the latter causes twitches and spastic tendencies.

These two symptoms are often severe enough to seriously disable an individual; among 36 people with Costeff syndrome, 17 experienced major motor disability as a result of choreoathetosis, and 12 experienced spasticity-related symptoms severe enough to do the same.

Ataxia (loss of muscle coordination) and speech impairment caused by dysarthria also occur in roughly 50% of cases, but are rarely seriously disabling.

Some individuals with Costeff disease also display mild cognitive impairment, though such cases are relatively infrequent.

Heřmanský–Pudlák syndrome (often written Hermansky–Pudlak syndrome or abbreviated HPS) is an extremely rare autosomal recessive disorder which results in oculocutaneous albinism (decreased pigmentation), bleeding problems due to a platelet abnormality (platelet storage pool defect), and storage of an abnormal fat-protein compound (lysosomal accumulation of ceroid lipofuscin).

It is considered to affect around 1 in 500,000 people worldwide, with a significantly higher occurrence in Puerto Ricans, with a prevalence of 1 in 1800. Many of the clinical research studies on the disease have been conducted in Puerto Rico.

There are eight classic forms of the disorder, based on the genetic mutation from which the disorder stems.

The appearance of people with the disorder is caused by a loss of bone in the mandible which the body replaces with excessive amounts of fibrous tissue. In most cases, the condition fades as the child grows, but in a few even rarer cases the condition continues to deform the affected person's face. Cherubism also causes premature loss of the primary teeth and uneruption of the permanent teeth.

The condition Cherubism is a rare autosomal dominant disease of the maxilla and mandible. Approximately 200 cases have been reported by medical journals with the majority being males. Cherubism is usually first diagnosed around age 7 and continues through puberty and may or may not continue to advance with age. The degrees of Cherubism vary from mild to severe. Osteoclastic and osteoblastic remodeling contributes to the change of normal bone to fibrous tissue and cyst formation. As noted by the name, the patient's face becomes enlarged and disproportionate due to the fibrous tissue and atypical bone formation. The sponge-like bone formations lead to early tooth loss and permanent tooth eruption problems. The condition also affects the orbital area, creating an upturned eye appearance. The cause of cherubism is believed to be traced to a genetic defect resulting from a mutation of the SH3BP2 gene from chromosome 4p16.3. While the condition is rare and painless, the afflicted suffer the emotional trauma of disfigurement. The effects of Cherubism may also interfere with normal jaw motion and speech. Currently, removal of the tissue and bone by surgery is the only treatment available. This condition is also one of the few that unexpectedly stops and regresses. Normal bone remodeling activity may resume after puberty.

Cherubism is displayed with genetic conformation and when excessive osteoclasts are found in the affected areas of the mandible and maxilla. Large cysts will be present with excessive fibrous areas inside the bone. The fibers and cysts will be found among the trabecula of the Coronoid process, the ramus of mandible, the body of mandible and the maxilla regions. The maxilla will be affected up to and including the orbits and sometimes inside the lower orbits. The maxilla and zygomatic bones are depressed and eyes appear to gaze upward. The maxilla has been found to be more severely affected in most cases than the mandible bone. Some patients found with lower inner orbital growths and cysts may lose vision.

Costeff syndrome, or 3-methylglutaconic aciduria type III, is a genetic disorder caused by mutations in the "OPA3" gene. It is typically associated with the onset of visual deterioration (optic atrophy) in early childhood followed by the development of movement problems and motor disability in later childhood, occasionally along with mild cases of cognitive deficiency. The disorder is named after Hanan Costeff, the doctor who first described the syndrome in 1989.

Usher syndrome is responsible for the majority of deaf-blindness. The word "syndrome" means that multiple symptoms occur together, in this case, deafness and blindness. It occurs in roughly 1 person in 23,000 in the United States, 1 in 28,000 in Norway and 1 in 12,500 in Germany. People with Usher syndrome represent roughly one-sixth of people with retinitis pigmentosa.

Usher syndrome is inherited in an autosomal recessive pattern. "Recessive" means both parents must contribute an appropriate gene for the syndrome to appear, and "autosomal" means the gene is not carried on one of the sex chromosomes (X or Y), but rather on one of the 22 other pairs. (See the article on human genetics for more details.)

The progressive blindness of Usher syndrome results from retinitis pigmentosa. The photoreceptor cells usually start to degenerate from the outer to the center of the retina, including the macula. The degeneration is usually first noticed as night blindness (nyctalopia); peripheral vision is gradually lost, restricting the visual field (tunnel vision), which generally progresses to complete blindness. The qualifier 'pigmentosa' reflects the fact that clumps of pigment may be visible by an ophthalmoscope in advanced stages of degeneration.

Although Usher syndrome has been classified clinically in several ways, the prevailing approach is to classify it into three clinical sub-types called Usher I, II and III in order of decreasing severity of deafness. Usher I and II are the more common forms; the fraction of people with Usher III is significant only in a few specific areas, such as Finland and Birmingham. As described below, these clinical subtypes may be further subdivided by the particular gene mutated; people with Usher I and II may have any one of six and three genes mutated, respectively, whereas only one gene has been associated with Usher III. The function of these genes is still poorly understood. The hearing impairment associated with Usher syndrome is better understood: damaged hair cells in the cochlea of the inner ear inhibit electrical impulses from reaching the brain.

The chemical imbalance is usually diagnosed when dental abnormalities are found. These abnormalities include premature deciduous teeth and abnormal growth of permanent teeth due to displacement by cysts and lesions. The only definite way to correctly diagnose the condition is by sequence analysis of the SH3BP2 gene. The gene has been found to have missense mutation in exon 9. Initial study of the patient is usually conducted using x-ray and CT scans. Neurofibromatosis may resemble Cherubism and may accompany the condition. Genetic testing is the final diagnosis tool.

Most patients with ML IV show psychomotor retardation (i.e., delayed development of movement and coordination), corneal opacity, retinal degeneration and other ophthalmological abnormalities. Other symptoms include agenesis of the corpus callosum, iron deficiency resulting from an absence of acid secretion in the stomach, achlorhydria. Achlorhydria in these patients results in an increase in blood gastrin levels. These symptoms typically manifest early in life (within the first year). After disease onset there occurs a period of stability, typically lasting two to three decades during which very little disease progression occurs.

Usher syndrome, also known as Hallgren syndrome, Usher-Hallgren syndrome, retinitis pigmentosa-dysacusis syndrome, or dystrophia retinae dysacusis syndrome, is an extremely rare genetic disorder caused by a mutation in any one of at least 11 genes resulting in a combination of hearing loss and visual impairment. It is a leading cause of deafblindness and is at present incurable.

Usher syndrome is classed into three subtypes according to onset and severity of symptoms. All three subtypes are caused by mutations in genes involved in the function of the inner ear and retina. These mutations are inherited in an autosomal recessive pattern.

The most distinctive clinical feature is the absence of overflow tears with emotional crying after age 7 months. This symptom can manifest less dramatically as persistent bilateral eye irritation. There is also a high prevalence of breech presentation. Other symptoms include weak or absent suck and poor tone, poor suck and misdirected swallowing, and red blotching of skin.

Symptoms in an older child with familial dysautonomia might include:

1. Delayed speech and walking

2. Unsteady gait

3. Spinal curvature

4. Corneal abrasion

5. Less perception in pain or temperature with nervous system.

6. Poor growth

7. Erratic or unstable blood pressure.

8. Red puffy hands

9. Dysautonomia crisis: a constellation of symptoms in response to physical and emotional stress; usually accompanied by vomiting, increased heart rate, increase in blood pressure, sweating, drooling, blotching of the skin and a negative change in personality.

Mucolipidosis type IV (ML IV or ML4) is an autosomal recessive lysosomal storage disorder. Individuals with the disorder have many symptoms including delayed psychomotor development and various ocular aberrations. The disorder is caused by mutations in the MCOLN1 gene, which encodes a non-selective cation channel, mucolipin1. These mutations disrupt cellular functions and lead to a neurodevelopmental disorder through an unknown mechanism. Researchers dispute the physiological role of the protein product and which ion it transports.

A clinical diagnosis of FD is supported by a constellation of criteria:

- No fungiform papillae on the tongue

- Decreased deep tendon reflexes

- Lack of an axon flare following intradermal histamine

- No overflow tears with emotional crying

Progeroid syndromes (PS) are a group of rare genetic disorders which mimic physiological aging, making affected individuals appear to be older than they are. The term "progeroid syndrome" does not necessarily imply progeria (Hutchinson–Gilford progeria syndrome), which is a specific type of progeroid syndrome.

"Progeroid" means "resembling premature aging", a definition that can apply to a broad range of diseases. Familial Alzheimer's disease and familial Parkinson's disease are two well-known accelerated-aging diseases that are more frequent in older individuals. They affect only one tissue and can be classified as unimodal progeroid syndromes. Segmental progeria, which is more frequently associated with the term "progeroid syndrome", tends to affect multiple or all tissues while causing affected individuals to exhibit only some of the features associated with aging.

All disorders within this group are thought to be monogenic, meaning they arise from mutations of a single gene. Most known PS are due to genetic mutations that lead to either defects in the DNA repair mechanism or defects in lamin A/C.

Examples of PS include Werner syndrome (WS), Bloom syndrome (BS), Rothmund–Thomson syndrome (RTS), Cockayne syndrome (CS), xeroderma pigmentosum (XP), trichothiodystrophy (TTD), combined xeroderma pigmentosum-Cockayne syndrome (XP-CS), restrictive dermopathy (RD), and Hutchinson–Gilford progeria syndrome (HGPS). Individuals with these disorders tend to have a reduced lifespan. Progeroid syndromes have been widely studied in the fields of aging, regeneration, stem cells, and cancer. The most widely studied of the progeroid syndromes are Werner syndrome and Hutchinson–Gilford progeria, as they are seen to most resemble natural aging.

Symptoms of the most common (and most serious) form of Canavan disease typically appear in early infancy usually between the first three to six months of age. Canavan disease then progresses rapidly from that stage, with typical cases involving intellectual disability, loss of previously acquired motor skills, feeding difficulties, abnormal muscle tone (i.e., floppiness or stiffness; hypotonia), poor head control, and megalocephaly (abnormally enlarged head). Paralysis, blindness, or seizures may also occur.

There exists a less common variant of Canavan disease which is generally much less serious, and involves later onset of symptoms, which are often mild and nonspecific enough to go unrecognized as manifestations of Canavan's disease. This variant does not seem to have any effect on lifespan, and is typically limited to minor cases of speech and motor skill development delay.

FA is characterized by bone marrow failure, AML, solid tumors, and developmental abnormalities. Classic features include abnormal thumbs, absent radii, short stature, skin hyperpigmentation, including café au lait spots, abnormal facial features (triangular face, microcephaly), abnormal kidneys, and decreased fertility. Many FA patients (about 30%) do not have any of the classic physical findings, but Diepoxybutane chromosome fragility assay showing increased chromosomal breaks can make the diagnosis. . About 80% of FA will develop bone marrow failure by age 20.

The first sign of a hematologic problem is usually petechiae and bruises, with later onset of pale appearance, feeling tired, and infections. Because macrocytosis usually precedes a low platelet count, patients with typical congenital anomalies associated with FA should be evaluated for an elevated red blood cell mean corpuscular volume.

In terms of the signs/symptoms of Fukuyama congenital muscular dystrophy it is characterized by a decrease in skeletal muscle tone as well as an impairment in brain and eye development.Initial symptoms of FCMD present in early infancy as decreased ability to feed. Marked differences in facial appearance occur due to decreased muscle tone. Further characteristics include:

- Seizures

- Delay in developmental

- Cardiac issues

- Swallowing difficulty

- Neurological problems

Fukuyama congenital muscular dystrophy also affects the nervous system and various associated parts. FCMD affects normal development of the brain producing a broadly smooth, bumpy shaped cortex named cobblestone lissencephaly as well as various other malformations, notably micropolygyria. Children also experience delayed myelination in the brain.

Adult polyglucosan body disease is a condition that affects the nervous system. People with this condition have problems walking due to reduced sensation in their legs (peripheral neuropathy) and progressive muscle weakness and stiffness (spasticity). Damage to the nerves that control bladder function, a condition called neurogenic bladder, causes affected individuals to have progressive difficulty controlling the flow of urine. About half of people with adult polyglucosan body disease experience a decline in intellectual function (dementia). Most people with the condition first go to the doctor due to the bladder issues.

People with adult polyglucosan body disease typically first experience signs and symptoms related to the condition between ages 30 and 60.

Laron's syndrome, or Laron-type dwarfism, is an autosomal recessive disorder characterized by an insensitivity to growth hormone (GH), usually caused by a mutant growth hormone receptor. It causes short stature and an increased sensitivity to insulin which means that they are less likely to develop diabetes mellitus type 2 and possibly cancer as well. It can be treated with injections of recombinant IGF-1.

Patients with Marfan-progeroid-lipodystrophy syndrome typically exhibit congenital lipodystrophy and a neonatal progeroid appearance. Sometimes identified as having neonatal progeroid syndrome, the term is a misnomer since they do not exhibit accelerated aging. The condition is caused by mutations near the 3'-terminus of the "FBN1" gene.