Symptoms include:

- Severe sunburn when exposed to only small amounts of sunlight. These often occur during a child's first exposure to sunlight.

- Development of many freckles at an early age

- Rough-surfaced growths (solar keratoses), and skin cancers

- Eyes that are painfully sensitive to the sun and may easily become irritated, bloodshot and clouded

- Blistering or freckling on minimum sun exposure

- Spider Veins

- Limited growth of hair on chest and legs

- Scaly skin

- Dry skin

- Irregular dark spots on the skin

- Corneal ulcerations

Xeroderma pigmentosum (XP) is a rare autosomal recessive genetic disorder of DNA repair in which the ability to repair damage caused by ultraviolet (UV) light is deficient. In extreme cases, "all" exposure to sunlight must be forbidden, no matter how small; as such, individuals with the disease are often colloquially referred to as "Moon children". Multiple basal cell carcinomas (basaliomas) and other skin malignancies frequently occur at a young age in those with XP; metastatic malignant melanoma and squamous cell carcinoma are the two most common causes of death in XP victims. This disease is present in both genders and in all races, with an incidence of 1:250,000 in the United States. XP is roughly six times more common in Japanese people than in other groups.

Normally, damage to DNA in epidermal cells occurs during exposure to UV light. The absorption of the high-energy light leads to the formation of pyrimidine dimers, namely cyclobutane-pyrimidine dimers and pyrimidine-6-4-pyrimidone photoproducts. In a healthy, normal human being, the damage is first excised by endonucleases. DNA polymerase then repairs the missing sequence, and ligase "seals" the transaction. This process is known as nucleotide excision repair.

A DNA repair-deficiency disorder is a medical condition due to reduced functionality of DNA repair.

DNA repair defects can cause an accelerated aging disease or an increased risk of cancer, or sometimes both.

Cockayne syndrome (CS), also called Neill-Dingwall syndrome, is a rare and fatal autosomal recessive neurodegenerative disorder characterized by growth failure, impaired development of the nervous system, abnormal sensitivity to sunlight (photosensitivity), eye disorders and premature aging. Failure to thrive and neurological disorders are criteria for diagnosis, while photosensitivity, hearing loss, eye abnormalities, and cavities are other very common features. Problems with any or all of the internal organs are possible. It is associated with a group of disorders called leukodystrophies, which are conditions characterized by degradation of neurological white matter. The underlying disorder is a defect in a DNA repair mechanism. Unlike other defects of DNA repair, patients with CS are not predisposed to cancer or infection. Cockayne syndrome is a rare but destructive disease usually resulting in death within the first or second decade of life. The mutation of specific genes in Cockayne syndrome is known, but the widespread effects and its relationship with DNA repair is yet to be well understood.

It is named after English physician Edward Alfred Cockayne (1880–1956) who first described it in 1936 and re-described in 1946. Neill-Dingwall syndrome was named after Mary M. Dingwall and Catherine A. Neill. These women described the case of two brothers with Cockayne syndrome and asserted it was the same disease described by Cockayne. In their article the women contributed to the symptoms of the disease through their discovery of calcifications in the brain. They also compared Cockayne syndrome to what is now known as Hutchinson–Gilford progeria syndrome (HGPS), then called progeria, due to the advanced aging that characterizes both disorders.

Many of the physical features associated with the disorder are congenital. Characteristic craniofacial abnormalities typically include a long, narrow head that is disproportionate to the body size, a broad and prominent forehead, and a triangular-shaped face with a hypoplastic midface, pointed chin, prominent mouth, fleshy tipped upturned nose, large ears, and full lips. The teeth may be abnormally crowded together in some affected individuals.

Individuals with 3-M syndrome suffer from severe prenatal growth retardation due to growth delays during fetal development resulting in a low birth weight. Growth delays continue after birth throughout childhood and adolescence, ultimately leading to a short stature.

Trichothiodystrophy (TTD) is an autosomal recessive inherited disorder characterised by brittle hair and intellectual impairment. The word breaks down into "tricho" – "hair", "thio" – "sulphur", and "dystrophy" – "wasting away" or literally "bad nourishment". TTD is associated with a range of symptoms connected with organs of the ectoderm and neuroectoderm. TTD may be subclassified into four syndromes: Approximately half of all patients with trichothiodystrophy have photosensitivity, which divides the classification into syndromes with or without photosensitivity; BIDS and PBIDS, and IBIDS and PIBIDS. Modern covering usage is TTD-P (photosensitive), and TTD.

Infants with this disorder appear normal at birth but usually develop signs and symptoms during the first year of life or in early childhood. The characteristic features of this condition, which can range from mild to life-threatening, include feeding difficulties, recurrent episodes of vomiting and diarrhea, excessive tiredness (lethargy), and weak muscle tone (hypotonia). If untreated, this disorder can lead to delayed development, seizures, and coma. Early detection and lifelong management (following a low-protein diet and using appropriate supplements) may prevent many of these complications. In some cases, people with gene mutations that cause 3-methylcrotonyl-CoA carboxylase deficiency never experience any signs or symptoms of the disorder.

The characteristic features of this condition are similar to those of Reye syndrome, a severe disorder that develops in children while they appear to be recovering from viral infections such as chicken pox or flu. Most cases of Reye syndrome are associated with the use of aspirin during these viral infections.

Onset of late infantile GM1 is typically between ages 1 and 3 years.

Neurological symptoms include ataxia, seizures, dementia, and difficulties with speech.

In at least some case, the gene lesion involves a mutation in the "CSB" gene.

It can be associated with "ERCC6".

The anemia associated with CDA type II can range from mild to severe, and most affected individuals have jaundice, hepatosplenomegaly, and the formation of hard deposits in the gallbladder called bilirubin gallstones. This form of the disorder is usually diagnosed in adolescence or early adulthood. An abnormal buildup of iron typically occurs after age 20, leading to complications including heart disease, diabetes, and cirrhosis.

Congenital dyserythropoietic anemia type II (CDA II), or hereditary erythroblastic multinuclearity with positive acidified serum lysis test (HEMPAS) is a rare genetic anemia in humans characterized by hereditary erythroblastic multinuclearity with positive acidified serum lysis test.

Symptoms of early infantile GM1 (the most severe subtype, with onset shortly after birth) may include neurodegeneration, seizures, liver enlargement (hepatomegaly), spleen enlargement (splenomegaly), coarsening of facial features, skeletal irregularities, joint stiffness, distended abdomen, muscle weakness, exaggerated startle response to sound, and problems with gait.

About half of affected patients develop cherry-red spots in the eye.

Children may be deaf and blind by age 1 and often die by age 3 from cardiac complications or pneumonia.

- Autosomal recessive disorder; beta-galactosidase deficiency; neuronal storage of GM1 ganglioside and visceral storage of galactosyl oligosaccharides and keratan sulfate.

- Early psychomotor deterioration: decreased activity and lethargy in the first weeks; never sit; feeding problems - failure to thrive; visual failure (nystagmus noted) by 6 months; initial hypotonia; later spasticity with pyramidal signs; secondary microcephaly develops; decerebrate rigidity by 1 year and death by age 1–2 years (due to pneumonia and respiratory failure); some have hyperacusis.

- Macular cherry-red spots in 50% by 6–10 months; corneal opacities in some

- Facial dysmorphology: frontal bossing, wide nasal bridge, facial edema (puffy eyelids); peripheral edema, epicanthus, long upper lip, microretrognathia, gingival hypertrophy (thick alveolar ridges), macroglossia

- Hepatomegaly by 6 months and splenomegaly later; some have cardiac failure

- Skeletal deformities: flexion contractures noted by 3 months; early subperiosteal bone formation (may be present at birth); diaphyseal widening later; demineralization; thoracolumbar vertebral hypoplasia and beaking at age 3–6 months; kyphoscoliosis. *Dysostosis multiplex (as in the mucopolysaccharidoses)

- 10–80% of peripheral lymphocytes are vacuolated; foamy histiocytes in bone marrow; visceral mucopolysaccharide storage similar to that in Hurler disease; GM1 storage in cerebral gray matter is 10-fold elevated (20–50-fold increased in viscera)

- Galactose-containing oligosacchariduria and moderate keratan sulfaturia

- Morquio disease Type B: Mutations with higher residual beta-galactosidase activity for the GM1 substrate than for keratan sulfate and other galactose-containing oligosaccharides have minimal neurologic involvement but severe dysostosis resembling Morquio disease type A (Mucopolysaccharidosis type 4).

Children with progeria usually develop the first symptoms during their first few months of life. The earliest symptoms may include a failure to thrive and a localized scleroderma-like skin condition. As a child ages past infancy, additional conditions become apparent usually around 18–24 months. Limited growth, full-body alopecia (hair loss), and a distinctive appearance (a small face with a shallow recessed jaw, and a pinched nose) are all characteristics of progeria. Signs and symptoms of this progressive disease tend to become more marked as the child ages. Later, the condition causes wrinkled skin, atherosclerosis, kidney failure, loss of eyesight, and cardiovascular problems. Scleroderma, a hardening and tightening of the skin on trunk and extremities of the body, is prevalent. People diagnosed with this disorder usually have small, fragile bodies, like those of elderly people. The face is usually wrinkled, with a larger head in relation to the body, a narrow face and a beak nose. Prominent scalp veins are noticeable (made more obvious by alopecia), as well as prominent eyes. Musculoskeletal degeneration causes loss of body fat and muscle, stiff joints, hip dislocations, and other symptoms generally absent in the non-elderly population. Individuals usually retain typical mental and motor development.

A cancer syndrome or family cancer syndrome is a genetic disorder in which inherited genetic mutations in one or more genes predispose the affected individuals to the development of cancers and may also cause the early onset of these cancers. Cancer syndromes often show not only a high lifetime risk of developing cancer, but also the development of multiple independent primary tumors. Many of these syndromes are caused by mutations in tumor suppressor genes, genes that are involved in protecting the cell from turning cancerous. Other genes that may be affected are DNA repair genes, oncogenes and genes involved in the production of blood vessels (angiogenesis). Common examples of inherited cancer syndromes are hereditary breast-ovarian cancer syndrome and hereditary non-polyposis colon cancer (Lynch syndrome).

Janus kinase 3 deficiency or JAK3 deficiency is a defect in the body's cytokine receptors and their signaling. JAK3 encodes Janus kinase 3, a tyrosine kinase that belongs to the Janus family. JAK3 functions in signal transduction and interacts with members of the STAT (signal transduction and activators of transcription) family. The cause of JAK3 deficiency. The deficiency causes the near absence of T lymphocytes and Natural killer cells; and normal or elevated B lymphocytes due to an autosomal recessive variant of severe combined immunodeficiency (SCID).

DeSanctis–Cacchione syndrome is an extremely rare disorder characterized by the skin and eye symptoms of xeroderma pigmentosum (XP) occurring in association with microcephaly, progressive mental retardation, retarded growth and sexual development, deafness, choreoathetosis, ataxia and quadriparesis.

DNA repair defects are seen in nearly all of the diseases described as accelerated aging disease, in which various tissues, organs or systems of the human body age prematurely. Because the accelerated aging diseases display different aspects of aging, but never every aspect, they are often called segmental progerias by biogerontologists.

Persons with this syndrome have smaller than normal head sizes (microcephaly), are of short stature (dwarfism), their eyes appear sunken, and they have an "aged" look. They often have long limbs with joint contractures (inability to relax muscle at a joint), a hunched back (kyphosis), and they may be very thin (cachetic), due to a loss of subcutaneous fat. Their small chin, large ears, and pointy, thin nose often give an aged appearance.

The skin of those with Cockayne syndrome is also frequently affected. Hyperpigmentation, varicose or spider veins (telangiectasia), and serious sensitivity to sunlight are common, even in individuals without XP-CS. Often patients with Cockayne Syndrome will severely burn or blister with very little exposure.

The eyes of patients can be affected in various ways and eye abnormalities are common in CS. Cataracts and cloudiness of the cornea (corneal opacity) are common. The loss of and damage to nerves of the optic nerve, causing optic atrophy can occur. Nystagmus, or involuntary eye movement, and pupils that fail to dilate demonstrate a loss of control of voluntary and involuntary muscle movement. A salt and pepper retinal pigmentation is also a visible symptom.

Diagnosis is determined by a specific test for DNA repair, which measures the recovery of RNA after exposure to UV radiation. Despite being associated with genes involved in nucleotide excision repair (NER), unlike xeroderma pigmentosum, CS is not associated with an increased risk of cancer.

A number of syndromes escape formal classification but are otherwise recognisable by particular clinical or immunological features.

1. Wiskott–Aldrich syndrome

2. DNA repair defects not causing isolated SCID: ataxia-telangiectasia, ataxia-like syndrome, Nijmegen breakage syndrome, Bloom syndrome

3. DiGeorge syndrome (when associated with thymic defects)

4. Various immuno-osseous dysplasias (abnormal development of the skeleton with immune problems): cartilage–hair hypoplasia, Schimke syndrome

5. Hermansky–Pudlak syndrome type 2

6. Hyper-IgE syndrome

7. Chronic mucocutaneous candidiasis

8. Hepatic venoocclusive disease with immunodeficiency (VODI)

9. XL-dyskeratosis congenita (Hoyeraal-Hreidarsson syndrome)

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.

Features of TTD can include photosensitivity, icthyosis, brittle hair and nails, intellectual impairment, decreased fertility and short stature. The acronyms PIBIDS, IBIDS, BIDS and PBIDS give the initials of the words involved. BIDS syndrome, also called Amish brittle hair brain syndrome and hair-brain syndrome, is an autosomal recessive inherited disease. It is nonphotosensitive. BIDS is characterized by brittle hair, intellectual impairment, decreased fertility, and short stature. There is a photosensitive syndrome, PBIDS.

BIDS is associated with the gene MPLKIP (TTDN1).

IBIDS syndrome, following the acronym from ichthyosis, brittle hair and nails, intellectual impairment and short stature, is the Tay syndrome or sulfur-deficient brittle hair syndrome, first described by Tay in 1971. (Chong Hai Tay was the Singaporean doctor who was the first doctor in South East Asia to have a disease named after him). Tay syndrome should not be confused with the Tay-Sachs disease. It is an autosomal recessive congenital disease. In some cases, it can be diagnosed prenatally. IBIDS syndrome is nonphotosensitive.

The photosensitive form is referred to as PIBIDS, and is associated with ERCC2 and ERCC3.

Progeria is an extremely rare genetic disorder in which symptoms resembling aspects of aging are manifested at a very early age. Progeria is one of several progeroid syndromes. Those born with progeria typically live to their mid-teens to early twenties. It is a genetic condition that occurs as a new mutation, and is rarely inherited, as carriers usually do not live to reproduce. Although the term progeria applies strictly speaking to all diseases characterized by premature aging symptoms, and is often used as such, it is often applied specifically in reference to Hutchinson–Gilford progeria syndrome (HGPS).

Progeria was first described in 1886 by Jonathan Hutchinson. It was also described independently in 1897 by Hastings Gilford. The condition was later named Hutchinson–Gilford progeria syndrome. The word "progeria" comes from the Greek words "pro" (), meaning "before" or "premature", and "gēras" (), meaning "old age". Scientists are interested in progeria partly because it might reveal clues about the normal process of aging.

3-Methylcrotonyl-CoA carboxylase deficiency (3MCC deficiency), also known as 3-Methylcrotonylglycinuria or BMCC deficiency is an inherited disorder in which the body is unable to process certain proteins properly. People with this disorder have inadequate levels of an enzyme that helps break down proteins containing the amino acid leucine. This condition affects an estimated 1 in 50,000 individuals worldwide.

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.