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.

Marfanoid–progeroid–lipodystrophy syndrome (MPL), also known as Marfan lipodystrophy syndrome (MFLS) or progeroid fibrillinopathy, is an extremely rare medical condition which manifests as a variety of symptoms including those usually associated with Marfan syndrome, an appearance resembling that seen in neonatal progeroid syndrome (NPS; also known as Wiedemann–Rautenstrauch syndrome), and severe partial lipodystrophy. It is a genetic condition that is caused by mutations in the "FBN1" gene, which encodes profibrillin, and affects the cleavage products of profibrillin, fibrillin-1, a fibrous structural protein, and asprosin, a glucogenic protein hormone. As of 2016, fewer than 10 cases of the condition have been reported. Lizzie Velasquez and Abby Solomon have become known publicly through the media for having the condition.

In addition to severe lipodystrophy (loss of adipose tissue), individuals with MPL show a concomitant marked loss of lean tissue mass, which also contributes to their "skinny" appearance. Based on visual inspection, it was originally thought that the lipodystrophy associated with MPL was generalized. However, it appears in fact to be partial, being confined to the face, distal extremities, and the and lateral regions of the buttocks. Normal amounts of subcutaneous fat are found in the torso over the chest and abdomen. As such, the breasts are normal in females with MPL.

Individuals with MPL have an appearance of being prematurely aged, but this is not due to actual early aging and is instead due to their paucity of subcutaneous fat. As such, MPL is not truly a form of progeria.

In 2016, it was discovered that the partial lipodystrophy associated with MPL is caused by loss of the C-terminal domain cleavage product of profibrillin and novel glucogenic protein hormone, which has been named asprosin. Due to asprosin deficiency, individuals with MPL eat less, and do not gain weight or develop symptoms of diabetes like insulin resistance. MPL patients burn less energy than normal individuals, but also consume less, and their net energy balance is moderately reduced. In contrast to MPL patients, whose asprosin is undetectable in the blood, individuals with obesity and diabetes have elevated levels of asprosin. As such, "FBN1" has been nicknamed the "thin gene", and drug development for targeted inhibition of asprosin signaling is considered to be an "unusually promising" potential therapeutic route in the treatment of obesity and diabetes.

There is no permanent cure for this syndrome, although patients can be treated according to their specific symptoms. The prognosis for those with Cockayne syndrome is poor, as death typically occurs by the age of 12. Treatment usually involves physical therapy and minor surgeries to the affected organs, like cataract removal. Also wearing high-factor sunscreen and protective clothing is recommended as patients with Cockayne syndrome are very sensitive to UV radiation. Optimal nutrition can also help. Genetic counseling for the parents is recommended, as the disorder has a 25% chance of being passed to any future children, and prenatal testing is also a possibility. Another important aspect is prevention of recurrence of CS in other sibling. Identification of gene defects involved makes it possible to offer genetic counseling and antenatal

diagnostic testing to the parents who already have one affected child.

CIPA is caused by a genetic mutation which prevents the formation of nerve cells which are responsible for transmitting signals of pain, heat, and cold to the brain. The disorder is autosomal recessive. It does not appear to have any particular ethnic distribution, though it is more prevalent in cultures in which intermarriage is an accepted practice. Overheating kills more than half of all children with CIPA before age 3.

The genetic mutation is in the gene encoding the neurotrophic tyrosine kinase receptor (SCN9A gene). NTRK1 is a receptor for nerve growth factor (NGF). This protein induces outgrowth of axons and dendrites and promotes the survival of embryonic sensory and sympathetic neurons. The mutation in NTRK1 does not allow NGF to bind properly, causing defects in the development and function of nociceptive reception.

Congenital insensitivity to pain with anhidrosis may be misdiagnosed for leprosy, based on similar symptoms of severe injuries to the hands and feet.

Congenital insensitivity to pain is found in Vittangi, a village in Kiruna Municipality in northern Sweden, where nearly 40 cases have been reported. A few Americans also have it.

In the United States, about 160,000 new cases of colorectal cancer are diagnosed each year. Hereditary nonpolyposis colorectal cancer is responsible for approximately 2 percent to 7 percent of all diagnosed cases of colorectal cancer. The average age of diagnosis of cancer in patients with this syndrome is 44 years old, as compared to 64 years old in people without the syndrome.

SJS is a rare condition, with a reported incidence of around 2.6 to 6.1 cases per million people per year. In the United States, about 300 new diagnoses are made each year. The condition is more common in adults than in children.

SJS (with less than 10% of body surface area involved) has a mortality rate of around 5%. The mortality for toxic epidermal necrolysis (TEN) is 30–40%. The risk for death can be estimated using the SCORTEN scale, which takes a number of prognostic indicators into account. It is helpful to calculate a SCORTEN within the first 3 days of hospitalization. Other outcomes include organ damage/failure, cornea scratching, and blindness.. Restrictive lung disease may develop in patients with SJS and TEN after initial acute pulmonary involvement. Patients with SJS or TEN caused by a drug have a better prognosis the earlier the causative drug is withdrawn.

It may be that the condition is caused by increased production of endorphins in the brain, in which case naloxone may be a treatment, but does not always work.

In all cases, this disorder can be in the voltage-gated sodium channel SCN9A (Na1.7). Patients with such mutations are congenitally insensitive to pain and lack other neuropathies. There are three mutations in SCN9A: W897X, located in the P-loop of domain 2; I767X, located in the S2 segment of domain 2; and S459X, located in the linker region between domains 1 and 2. This results in a truncated non-functional protein. Na1.7 channels are expressed at high levels in nociceptive neurons of the dorsal root ganglia. As these channels are likely involved in the formation and propagation of action potentials in such neurons, it is expected that a loss of function mutation in SCN9A leads to abolished nociceptive pain propagation.

PRDM12 gene is normally switched on during the development of pain-sensing nerve cells. People with homozygous mutations of the PRDM12 gene experience congenital insensitivity to pain (CIP).

Developmental disabilities such as autism can include varying degrees of pain insensitivity as a sign. However, since these disorders are characterized by dysfunction of the sensory system in general, this specific condition is not in itself an indicator of any of these conditions.

CCCA tends to present itself in the 20s and progresses over 20–30 years. One should consider this diagnosis in African Americans with what appears to be a female-pattern hair loss.

Hunan hand syndrome (also known as "Chili burn") is a cutaneous condition and commonly among those who remove the skins from large batches of roasted chili peppers.

Not all newborns that are SGA are pathologically growth restricted and, in fact, may be constitutionally small. If small for gestational age babies have been the subject of intrauterine growth restriction (IUGR), formerly known as intrauterine growth retardation, the term SGA associated with IUGR is used.

Intrauterine growth restriction (IUGR) refers to a condition in which a fetus is unable to achieve its genetically determined potential size. This functional definition seeks to identify a population of fetuses at risk for modifiable but otherwise poor outcomes. This definition intentionally excludes fetuses that are small for gestational age (SGA) but are not pathologically small. Infants born SGA with severe short stature (or severe SGA) are defined as having a length less than 2.5 standard deviation scores below the mean.

A related term is low birth weight (LBW), defined as an infant with a birth weight (that is, mass at the time of birth) of less than 2500 g (5 lb 8 oz), regardless of gestational age at the time of birth.

Related definitions include very low birth weight (VLBW) which is less than 1500 g, and extremely low birth weight (ELBW) which is less than 1000 g. Normal Weight at term delivery is 2500 g - 4200 g.

SGA is not a synonym of LBW, VLBW or ELBW.

Example: 35-week gestational age delivery, 2250g weight is appropriate for gestational age but is still LBW. One third of low-birth-weight neonates - infants weighing less than 2500g - are small for gestational age.

There is an 8.1% incidence of low birth weight in developed countries, and 6–30% in developing countries. Much of this can be attributed to the health of the mother during pregnancy. One third of babies born with a low birth weight are also small for gestational age. Infants that are born at low birth weights are at risk of developing neonatal infection.

Both low and high maternal serum Vitamin D (25-OH) are associated with higher incidence SGA in white women, although the correlation does not seem to hold for African American women.

The mortality for toxic epidermal necrolysis is 25-30%. People with SJS or TEN caused by a medications have a better prognosis the earlier the causative medication is withdrawn. Loss of the skin leaves patients vulnerable to infections from fungi and bacteria, and can result in sepsis, the leading cause of death in the disease. Death is caused either by infection or by respiratory distress which is either due to pneumonia or damage to the linings of the airway. Microscopic analysis of tissue (especially the degree of dermal mononuclear inflammation and the degree of inflammation in general) can play a role in determining the prognosis of individual cases.

Small for gestational age (SGA) newborns are those who are smaller in size than normal for the gestational age, most commonly defined as a weight below the 10th percentile for the gestational age.

Acroosteolysis is resorption of the distal bony phalanges. Acroosteolysis has two patterns of resorption in adults: diffuse and bandlike.

The diffuse pattern of resorption has a widely diverse differential diagnosis which includes: pyknodysostosis, collagen vascular disease and vasculitis, Raynaud's neuropathy, trauma, epidermolysis bullosa, psoriasis, frostbite, sarcoidosis, hypertrophic osteoarthropathy, acromegaly, and advanced leprosy.

The bandlike pattern of resorption may be seen with polyvinyl chloride exposure and Hadju-Cheney syndrome.

A mnemonic commonly used for acro-osteolysis is PINCHFO.

Pyknodysostosis, Psoriasis,

Injury (thermal burn, frostbite),

Neuropathy (diabetes),

Collagen vascular disease (scleroderma, Raynaud's),

Hyperparathyroidism,

Familial (Hadju-Cheney, progeria),

Occupational (polyvinyl exposure),

Acroosteolysis may be associated with minimal skin changes or with ischemic skin lesions that may result in digital necrosis.

IBS is an autosomal dominant genetic condition caused by a mutation in the gene for keratin 2e on chromosome 12.

This means an affected person has a 50% chance of passing the condition on to their child. Around half of cases of IBS, however, have no parent with the condition and have the genetic fault due to a spontaneous mutation.

The mechanism of pathology of CCCA has only been postulated and not proven. However, one theory involves pressure exerted on the internal root sheath leading to damage, which leads to the recruitment of inflammatory cells and the end result of scarring. African Americans are found to be at increased risk either because of the curled hair shaft, distinct styling practices, moisturizing hair products, or chemical processing techniques (especially in the youth population). Some have hypothesized that CCCA represents an end stage of traction alopecia. However, this theory does not ring true as many patients lack a report of traction hairstyling.

Five types of syndactyly have been identified in humans. The corresponding loci associated with these types and their common phenotypical expression are as follows:

- "type I": 2q34-q36; webbing occurs between middle and ring fingers and/or second and third toes.

- "type II": 2q31; also involves long and ring fingers, but has a sixth finger merged in between.

- "type III": 6q21-q23; small finger is merged into the ring finger.

- "type IV": 7q36; involves all fingers and/or toes.

- "type V": 2q31-q32; similar to type I, but the metacarpals and metatarsals may also be fused.

The most common problem with syndactyly correction is creeping of the skin towards the fingertip over time. This is likely due to tension at the site of the repair between the digits. Additional surgery may be required to correct this. One critique of using skin grafts is that the grafts darken in the years after surgery and become more noticeable. Also, if the skin grafts are harvested from the groin area, the skin may grow hair. Finally, the fingers may deviate after surgery. This is most commonly seen in complex syndactyly (when there has been a bony joining of the fingers).

Since hyperinsulinemia and obesity are so closely linked it is hard to determine whether hyperinsulinemia causes obesity or obesity causes hyperinsulinemia, or both.

Obesity is characterized by an excess of adipose tissue – insulin increases the synthesis of fatty acids from glucose, facilitates the entry of glucose into adipocytes and inhibits breakdown of fat in adipocytes.

On the other hand, adipose tissue is known to secrete various metabolites, hormones and cytokines that may play a role in causing hyperinsulinemia. Specifically cytokines secreted by adipose tissue directly affect the insulin signalling cascade, and thus insulin secretion. Adiponectins are cytokines that are inversely related to percent body fat; that is people with a low body fat will have higher concentrations of adiponectins where as people with high body fat will have lower concentrations of adiponectins. Weyer "et al." (2011) reported that hyperinsulinemia is strongly associated with low adiponectin concentrations in obese people, though whether low adiponectin has a causal role in hyperinsulinemia remains to be established.

- May lead to hypoglycemia or diabetes

- Increased risk of PCOS

- Increased synthesis of VLDL (hypertriglyceridemia)

- Hypertension (insulin increases sodium retention by the renal tubules)

- Coronary Artery Disease (increased insulin damages endothelial cells)

- Increased risk of cardiovascular disease

- Weight gain and lethargy (possibly connected to an underactive thyroid)

Ichthyosis bullosa of Siemens is a type of familial, autosomal dominant ichthyosis, a rare skin disorder. It is also known as bullous congenital ichthyosiform erythroderma of Siemens or ichthyosis exfoliativa. It is a genetic disorder with no known cure which is estimated to affect about 1 in 500,000 people.

Surgery remains the front-line therapy for HNPCC. There is an ongoing controversy over the benefit of 5-fluorouracil-based adjuvant therapies for HNPCC-related colorectal tumours, particularly those in stages I and II.

Infection-related cutaneous conditions may be caused by bacteria, fungi, yeast, viruses, or parasites.

AC is caused by chronic and excessive exposure to ultraviolet radiation in sunlight.

Risk factors include:

- Outdoor lifestyle: e.g. farmers, sailors, fishermen, windsurfers, mountaineers, golfers, etc. This has given rise to synonyms for this condition such as "sailor's lip" and "farmer's lip". The prevalence in agricultural workers in a semi-arid region of Brazil is reported to be 16.7%.

- Light skin complexion: the condition typically affects individuals with lighter skin tones, particularly Caucasians living in tropical regions. In one report, 96% of persons with AC had phenotype II according to the Fitzpatrick scale.

- Age: AC typically affects older individuals, and rarely those under the age of 45.

- Gender: the condition affects males more commonly than females. Sometimes this ratio is reported as high as 10:1.

Additional factors may also play a role, including tobacco use, lip irritation, poor oral hygiene, and ill-fitting dentures.