Wolcott–Rallison syndrome, WRS, is a rare, autosomal recessive disorder with infancy-onset diabetes mellitus, multiple epiphyseal dysplasia, osteopenia, mental retardation or developmental delay, and hepatic and renal dysfunction as main clinical findings. Patients with WRS have mutations in the EIF2AK3 gene, which encodes the pancreatic eukaryotic translation initiation factor 2-alpha kinase 3.

Physical examination findings in patients with CDGP are essentially normal, with the exception of immature appearance for age. Body proportions may reflect the delay in growth. During childhood, the upper-to-lower body ratio may be greater than normal, reflecting more infantile proportions. In adults, the ratio is often reduced (i.e., <1 in whites, <0.9 in blacks) as a result of the longer period of leg (long bone) growth.

Symptoms for Alström syndrome generally appear during infancy with great variability in age. Some of the symptoms include:

- Heart failure (Dilated cardiomyopathy) in over 60% of cases, usually within the first few weeks after birth, but sometimes the onset is in adolescence or adulthood.

- Light sensitivity and vision problems (Cone-rod dystrophy) in all cases, usually within 15 months of birth and progressively worsening until about 20 years of age

- Delays in early, developmental milestones in 50% of cases, learning disabilities in about 30% of cases

- Obesity in 100% of cases, apparent by 5 years of age, but often apparent in infancy (Alström infants usually have normal birth weights, and by adolescence, weights tend to be in the high-normal to normal range)

- Nystagmus (usually affects the children) one of the first symptoms to occur which causes involuntary rapid eye movement.

- Heart failure (Dilated cardiomyopathy) in over 60% of cases, usually within the first few weeks after birth, but sometimes the onset is in adolescence or adulthood.(chronic)

- Mild to moderate bilateral sensorineural hearing loss.

- Type 2 diabetes usually occurs in early childhood.

- Hyperinsulinemia/ insulin resistance—development of high level of insulin in blood.

- Steatosis (fatty liver) and elevated transaminases (liver enzymes) often develop in childhood and can progress in some patients to cirrhosis and liver failure.

- Endocrine dysfunctions may occur where the patient may experience an under or over active thyroid gland, weak growth hormone, increased androgen in females, and low testosterone in males.

- Slowly progressive kidney failure can occur in the second to fourth decade of life.

Children with constitutional delay of growth and puberty (CDGP), the most common cause of short stature and pubertal delay in males, typically have slowed linear growth within the first 3 years of life. In this variant of normal growth, linear growth velocity and weight gain slows beginning as young as age 3–6 months, resulting in downward crossing of growth percentiles, which often continues until age 2–3 years. At that time, growth resumes at a normal rate, and these children grow either along the lower growth percentiles or beneath the curve but parallel to it for the remainder of the prepubertal years.

At the expected time of puberty, the height of children with CDGP begins to drift further from the growth curve because of delay in the onset of the pubertal growth spurt. Catch-up growth, onset of puberty, and pubertal growth spurt occur later than average, resulting in normal adult stature and sexual development. Although CDGP is a variant of normal growth rather than a disorder, delays in growth and sexual development may contribute to psychological difficulties, warranting treatment for some individuals. Recent studies have suggested that referral bias is largely responsible for the impression that normal short stature per se is a cause of psycho-social problems; non-referred children with short stature do not differ from those with more normal stature in school performance or socialization.

Duarte galactosemia (also known as Duarte variant galactosemia, DG, or biochemical variant galactosemia) is an inherited condition associated with diminished ability to metabolize galactose due to a partial deficiency of the enzyme galactose-1-phosphate uridylyltransferase. Duarte galactosemia (DG) is estimated to affect close to one in 4,000 infants born in the United States. DG Is considered by most healthcare professionals to be clinically mild. It differs from classic galactosemia in that patients with Duarte galactosemia have partial GALT deficiency whereas patients with classic galactosemia have complete, or almost complete, GALT deficiency.

DG, and the possible outcomes associated with this condition, are currently not well understood. Due to regional variations in newborn screening (NBS) protocols, some infants with DG are identified by NBS but others are not. In addition, of the infants who are diagnosed, most are clinically healthy as babies and toddlers, resulting in early discharge from follow up. Many healthcare professionals believe that DG does not negatively impact development. However, some reports have indicated that children with DG may be at increased risk for some developmental problems.

Initially, patients with neonatal or early-childhood onset diabetes are possible candidates for having Wolcott–Rallison syndrome. The other symptoms include the multiple epiphyseal dysplasia, osteopenia, intellectual disability, and hepatic and renal dysfunction. Patients with the symptoms that line up with Wolcott–Rallison syndrome can be suggested for genetics testing. The key way to test for this disease specifically is through genetic testing for the EIKF2AK3 mutation. Molecular genetic analysis can be done for the patient and the parents to test for de novo mutations or inherited. It can also show whether the patient's parents are heterozygotes or homozygotes for the normal phenotype. X-Rays can show bone age in relation to actual age. Typically the bond age is a few years less than the actual in the patients with WRS. Hypothyroidism is rare is WRS patients but can occur.

Alström syndrome, also called Alstrom-Halgren syndrome, is a rare genetic disorder caused by mutations in the gene ALMS1. It is among the rarest genetic disorders in the world, as currently it has only 266 reported cases in medical literature and over 501 known cases in 47 countries. It was first described by Carl-Henry Alström in Sweden in 1959. Alstrom syndrome is sometimes confused with Bardet-Biedl syndrome, which has similar symptoms. Bardet-Biedl syndrome tends to have later onset in its symptoms. The likelihood of two carrier parents both passing the gene and therefore having a child affected by the syndrome is 25% with each pregnancy. The likelihood of having a child who is only a carrier of the gene is 50% with each pregnancy. The likelihood of a child receiving normal genes from both parents and being considered to be "genetically" normal is 25%. The risk for carrying the gene is equivalent for both males and females.

"Alström syndrome (AS) is a rare autosomal recessive disease characterized by multiorgan dysfunction. The key features are childhood obesity, blindness due to congenital retinal dystrophy, and sensorineural hearing loss. Associated endocrinologic features include hyperinsulinemia, early-onset type 2 diabetes, and hypertriglyceridemia."

Thus, AS shares several features with the common metabolic syndrome, namely obesity, hyperinsulinemia, and hypertriglyceridemia. Mutations in the ALMS1 gene have been found to be causative for AS with a total of 79 disease-causing mutations having been described." Prevalence estimates have ranged from 1 in 10,000 to fewer than 1 in 1,000,000 individuals in the general population.

MODY 4 is a form of maturity onset diabetes of the young.

MODY 4 arises from mutations of the PDX1 homeobox gene on chromosome 13. Pdx-1 is a transcription factor vital to the development of the embryonic pancreas. Even in adults it continues to play a role in the regulation and expression of genes for insulin, GLUT2, glucokinase, and somatostatin.

MODY 4 is so rare that only a single family has been well-studied. A child born with pancreatic agenesis (absence of the pancreas) was found to be homozygous for Pdx-1 mutations. A number of older relatives who were heterozygous had mild hyperglycemia or diabetes. None were severely insulin-deficient and all were controlled with either diet or oral hypoglycemic agents.

Infants with DG show an impaired ability to metabolize galactose, a sugar found at high levels in breast milk, milk formula, and most dairy products. Galactose is found at low levels in many fruits, vegetables, and other foods. Galactose is also produced at low levels by the human body.

Infants with DG, who consume breast milk or formula containing the milk sugar, lactose, are usually, but not always, asymptomatic. Infants who do show symptoms, such as jaundice, typically recover quickly when switched to a low-lactose diet, such as soy formula.

TBS patients may have the following symptoms:

- Abnormalities of the external ears (unusually large or small, unusually shaped, sometimes with sensorineural hearing loss or deafness due to lesions or dysfunctions of part of the internal ear or its nerve tracts and centers or conductive hearing loss from the external or middle ear), dysplastic ears, lop ear (over-folded ear helix), preauricular tags or pits (a rudimentary tag of ear tissue typically located just in front of the ear).

- Anorectal malformations, including imperforate anus/absence of an anal opening, rectovaginal fistula, anal stenosis, unusually placed anus.

- Renal abnormalities, sometimes leading to impaired renal function or renal failure, including hypoplastic kidneys (underdeveloped), multicystic kidneys, dyspastic kidneys.

- Heart abnormalities, including tetralogy of fallot and defects of the ventricular septum.

- Hand and foot abnormalities, such as hypoplastic thumbs, fingerlike thumbs, syndactyly (webbed fingers/toes), fusion of the wrist bones, overlapping foot and/or toe bones.

Learning difficulties have been reported in some children with TBS. For others, intelligence is within the normal range.

These abnormalities, which are present prenatally, can range from minor to severe, and as with similar disorders, most individuals with this condition have some, but not all, of these traits.

Oculocerebrorenal syndrome (also called Lowe syndrome) is a rare X-linked recessive disorder characterized by congenital cataracts, hypotonia, intellectual disability, proximal tubular acidosis, aminoaciduria, and low-molecular-weight proteinuria. Lowe syndrome can be considered a cause of Fanconi syndrome (bicarbonaturia, renal tubular acidosis, potassium loss, and sodium loss).

Because oculocerebrorenal syndrome is an X-linked recessive condition, the disease develops mostly in men with very rare occurrences in women, while women are carriers of the disease; it has an estimated prevalence of 1 in 500,000 people. Boys with Lowe syndrome are born with cataracts in both eyes, glaucoma is present in about half of the individuals with Lowe syndrome, though usually not at birth. While not present at birth, many affected boys develop kidney problems at about one year of age. Renal pathology is characterized by an abnormal loss of certain substances into the urine, including bicarbonate, sodium, potassium, amino acids, organic acids, albumin, calcium and L-carnitine, this problem, is known as Fanconi-type renal tubular dysfunction.

Townes–Brocks syndrome (TBS) is a rare genetic disease that has been described in approximately 200 cases in the published literature. It affects both males and females equally. The condition was first identified in 1972. by Philip L. Townes, MD, PhD, who was at the time a human geneticists and Professor of Pediatrics, and Eric Brocks, MD, who was at the time a medical student, both at the University of Rochester.

Wolfram syndrome, also called DIDMOAD (diabetes insipidus, diabetes mellitus, optic atrophy, and deafness), is a rare autosomal-recessive genetic disorder that causes childhood-onset diabetes mellitus, optic atrophy, and deafness as well as various other possible disorders.

It was first described in four siblings in 1938 by Dr. Don J. Wolfram, M.D. The disease affects the central nervous system (especially the brainstem).

MODY 6 is a form of maturity onset diabetes of the young.

MODY 6 arises from mutations of the gene for the transcription factor referred to as neurogenic differentiation 1. The gene is on chromosome 2 in a region of the p arm known as IDDM7 because it includes genes affecting susceptibility to type 1 diabetes. NeuroD1 promotes transcription of the insulin gene as well as some genes involved in formation of beta cells and parts of the nervous system.

This is also one of the rarer forms of MODY. Only 3 kindreds with mutations causing MODY6 have been identified so far. In both, some of the members had more typical type 2 diabetes rather than MODY, and the reasons for the difference of expression have not been worked out. Most of the family members with diabetes were diagnosed after age 40, but a few required insulin for blood sugar control.

"Common symptoms of NDM includes:"

- Thirst and Frequent Urination

An excessive thirst (also known as polydipsia) and increased urination (also known as polyuria) are common signs of diabetes. An individual with diabetes, have accumulated blood glucose. Their kidneys are working overtime to filter and uptake excess sugar. However, their kidneys cannot keep up, excess sugar is excreted into their urine, and this drag along fluids from the diabetic's tissues. This may lead to more frequent urination and lead to dehydration. As a diabetic individual drinks more fluids to satisfy their thirst, he or she urinates even more.

- Dehydration

Effected areas of the body are the eyes, mouth, kidneys, heart, and pancreas. Other symptoms of dehydration includes headache, thirst and dry mouth, dizziness, tiredness, and dark colored urine. In severe cases of dehydration in diabetics, low blood pressure, sunken eyes, a weak pulse or rapid heart beat, feeling confused or fatigue. Dehydration and high blood glucose for extended period of time, the diabetic's kidney would try to filter the blood of access glucose and excrete this as urine. As the kidneys are filtering the blood, water is being removed from the blood and would need to be replaced. This leads to an increased thirst when the blood glucose is elevated in a diabetic individual. Water is needed to re-hydrate the body. Therefore, the body would take available from other parts of the body, such as saliva, tears, and from cells of the body. If access water is not available, the body would not be able to pass excess glucose out of the blood by urine and can lead to further dehydration.

"Severe symptoms of NDM (Deficiency of insulin):"

- Ketoacidosis

Is a diabetic complication that occurs when the body produces high levels of acid in the blood (ketones). This effects the pancreas, fat cells, and kidneys. This condition occurs when the body cannot produce enough insulin. In the absence or lack of insulin, the body of an diabetic individual will break down fat as fuel. This process produces a buildup of acids in the bloodstream known as ketones, in which leads to ketoacidosis if left untreated. The symptoms of ketoacidosis develop rapidly or within 24 hours. Symptoms of ketoacidosis are excessive thirst, frequent urination, nausea or vomiting, stomach pain, tiredness, shortness or fruity smell on breath and confusion.

- Intrauterine Growth Restriction

A condition in which the unborn baby is smaller than he or she should be, due to the fact he or she not growing at a normal rate in the womb. Delayed growth puts the baby at risk of certain problems during pregnancy, delivery, and after birth. The problems are as follows: baby's birth weight is 90% less than normal weight, difficulty handling vaginal delivery, decreased oxygen levels, hypoglycemia (low blood glucose), low resistance to infection, low Apgar scores (a test given after birth to test the baby's physical condition and evaluate if special medical care is needed), Meconium aspiration (inhaling of stools passed while in the uterus) which causes breathing issues, irregular body temperature and high red blood cell count.

- Hyperglycemia

A condition characterized as high blood glucose, which occurs when the body has too little insulin or when the body cannot use insulin properly. Hyperglycemia affects the pancreas, kidneys, and body's tissues. Characterization of hyperglycemia is high blood glucose, high levels of sugar in the urine, frequent urination and increase thirst.

- Hypoglycemia

A condition characterized an extremely low blood glucose, usually less than 70 mg/dL. Areas of the body that are affected, pancreas, kidneys, and mental state.

Werner syndrome patients exhibit growth retardation, short stature, premature graying of hair, alopecia (hair loss), wrinkling, prematurely aged faces with beaked noses, skin atrophy (wasting away) with scleroderma-like lesions, lipodystrophy (loss of fat tissues), abnormal fat deposition leading to thin legs and arms, and severe ulcerations around the Achilles tendon and malleoli (around ankles). Other symptoms include change in voice (weak, hoarse, high-pitched), atrophy of gonads leading to reduced fertility, bilateral cataracts (clouding of lens), premature arteriosclerosis (thickening and loss of elasticity of arteries), calcinosis (calcium deposits in blood vessels), atherosclerosis (blockage of blood vessels), type 2 diabetes, osteoporosis (loss of bone mass), telangiectasia, and malignancies. The prevalence of rare cancers, such as meningiomas, are increased in individuals with Werner syndrome.

Renal cysts and diabetes syndrome (RCAD), also known as MODY 5, is a form of maturity onset diabetes of the young.

HNF1β-related MODY is one of the less common forms of MODY, with some distinctive clinical features, including atrophy of the pancreas and several forms of renal disease. HNF1β, also known as transcription factor 2 (TCF2), is involved in early stages of embryonic development of several organs, including the pancreas, where it contributes to differentiation of pancreatic endocrine Ngn3 cell progenitors from non-endocrine embryonic duct cells. The gene is on chromosome 17q.

The degree of insulin deficiency is variable. Diabetes can develop from infancy through middle adult life, and some family members who carry the gene remain free of diabetes into later adult life. Most of those who develop diabetes show atrophy of the entire pancreas, with mild or subclincal deficiency of exocrine as well as endocrine function.

The non-pancreatic manifestations are even more variable. Kidney and genitourinary malformation and diseases may occur, but inconsistently even within a family, and the specific conditions include a range of apparently unrelated anomalies and processes. The most common genitourinary condition is cystic kidney disease, but there are many varieties even of this. Renal effects begin with structural alterations (small kidneys, renal cysts, anomalies of the renal pelvis and calices), but a significant number develop slowly progressive renal failure associated with chronic cystic disease of the kidneys. In some cases, renal cysts may be detected in utero. Kidney disease may develop before or after hyperglycemia, and a significant number of people with MODY5 are discovered in renal clinics.

With or without kidney disease, some people with forms of HNF1β have had various minor or major anomalies of the reproductive system. Male defects have included epididymal cysts, agenesis of the vas deferens, or infertility due to abnormal spermatozoa. Affected women have been found to have vaginal agenesis, hypoplastic, or bicornuate uterus.

Liver enzyme elevations are common, but clinically significant liver disease is not. Hyperuricaemia and early onset gout have occurred.

Neonatal diabetes mellitus (NDM) is defined as a disease that affects an infant and their body's ability to produce or use insulin. NDM is a monogenic (controlled by a single gene) form of diabetes that occurs in the first 6 months of life. Infants do not produce enough insulin, leading to an increase in . It is a rare disease, occurring in only one in 100,000 to 500,000 live births. NDM can be mistaken for the much more common type 1 diabetes, but type 1 diabetes usually occurs later than the first 6 months of life. There are two types of NDM: permanent neonatal diabetes mellitus (PNDM) is a lifelong condition. Transient neonatal diabetes mellitus (TNDM) is diabetes that disappears during the infant stage but may reappear later in life.

Specific genes that can cause NDM have been identified. The onset of NDM can be caused by abnormal pancreatic development, beta cell dysfunction or accelerated beta cell dysfunction. Individuals with monogenic diabetes can pass it on to their children or future generations. Each gene associated with NDM has a different inheritance pattern.

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.

MODY 1 is a form of maturity onset diabetes of the young.

MODY 1 is due to a loss-of-function mutation in the gene on chromosome 20. This gene codes for HNF4-α protein also known as transcription factor 14 (TCF14). HNF4α controls function of HNF1α (see MODY 3; ) and perhaps HNF1β (MODY 5) as well. This transcription network plays a role in the early development of the pancreas, liver, and intestines. In the pancreas these genes influence expression of, among others, the genes for insulin, the principal glucose transporter (GLUT2), and several proteins involved in glucose and mitochondrial metabolism.

Although pancreatic beta cells produce adequate insulin in infancy, the capacity for insulin production declines thereafter. Diabetes (persistent hyperglycemia) typically develops by early adult years, but may not appear until later decades. The degree of insulin deficiency is slowly progressive. Many patients with MODY 1 are treated with sulfonylureas for years before insulin is required.

Liver effects are subtle and not clinically significant. Many people with this condition have low levels of triglycerides, lipoprotein(a), apolipoproteins AII and CIII.

Mutations in the alternative promoter of HNF4A are linked to development of type 2 diabetes.

The mutation in the WRN gene that causes Werner syndrome is autosomal and recessive, meaning that sufferers must inherit a copy of the gene from each parent. Patients display rapid premature aging beginning in young adulthood, usually in their early twenties. Diagnosis is based on six cardinal symptoms: premature graying of the hair or hair loss, presence of bilateral cataracts, atrophied or tight skin, soft tissue calcification, sharp facial features, and an abnormal, high-pitched voice. Patients are also generally short-statured due to absence of the adolescent growth spurt. Patients also display decreased fertility. The most common symptom of the six is premature graying and loss of hair. This is also generally the earliest observed symptom, with hair loss occurring first on the scalp and the eyebrows.

Werner syndrome patients often have skin that appears shiny and tight, and may also be thin or hardened. This is due to atrophy of the subcutaneous tissue and dermal fibrosis. Over time, facial features may be more apparent due to these skin conditions. Other associated skin conditions include ulcers, which are very difficult to treat in Werner syndrome patients, and are caused in part by decreased potential of skin cells for replication.

WS cataracts are distinctly different from those of normal aging. They are associated with problems in the lens posterior cortex and subcapsular regions. These cataracts are generally treatable with cataract surgery, which should restore normal vision.

Symptoms become apparent in the late teens and early twenties and continue to progress. Most patients live to about fifty years of age. The most common causes of death for people are associated diseases and complications, especially atherosclerosis and cancer.

In contrast to Hartnup disease and related tubular conditions, Fanconi syndrome affects the transport of many different substances, so is not considered to be a defect in a specific channel, but a more general defect in the function of the proximal tubules.

Different diseases underlie Fanconi syndrome; they can be inherited, congenital, or acquired.

The clinical features of proximal renal tubular acidosis are:

- Polyuria, polydipsia and dehydration

- Hypophosphatemic rickets (in children) and osteomalacia (in adults)

- Growth failure

- Acidosis

- Hypokalemia

- Hyperchloremia

Other features of the generalized proximal tubular dysfunction of the Fanconi syndrome are:

- Hypophosphatemia/hyperphosphaturia

- Glycosuria

- Proteinuria/aminoaciduria

- Hyperuricosuria

Of the following common symptoms of Turner syndrome, an individual may have any combination of symptoms and is unlikely to have all symptoms.

- Short stature

- Lymphedema (swelling) of the hands and feet of a newborn

- Broad chest (shield chest) and widely spaced nipples

- Low posterior hairline

- Low-set ears

- Reproductive sterility

- Rudimentary ovaries gonadal streak (underdeveloped gonadal structures that later become fibrotic)

- Amenorrhoea, the absence of a menstrual period

- Increased weight, obesity

- Shortened metacarpal IV

- Small fingernails

- Characteristic facial features

- Webbed neck from cystic hygroma in infancy

- Aortic valve stenosis

- Coarctation of the aorta

- Bicuspid aortic valve (most common cardiac problem)

- Horseshoe kidney

- Visual impairments – sclera, cornea, glaucoma, etc.

- Ear infections and hearing loss

- High waist-to-hip ratio (the hips are not much bigger than the waist)

- Attention deficit hyperactivity disorder (problems with concentration, memory, attention with hyperactivity seen mostly in childhood and adolescence)

- Nonverbal learning disability (problems with maths, social skills, and spatial relations)

Other features may include a small lower jaw (micrognathia), cubitus valgus, soft upturned nails, palmar crease, and drooping eyelids. Less common are pigmented moles, hearing loss, and a high-arch palate (narrow maxilla). Turner syndrome manifests itself differently in each female affected by the condition; therefore, no two individuals share the same features.

While most of the physical findings are harmless, significant medical problems can be associated with the syndrome. Most of these significant conditions are treatable with surgery and medication.