Conorenal syndrome, also called Mainzer-Saldino syndrome or Saldino-Mainzer disease, is a collection of medical conditions that seem to have a common genetic cause.

It is a genetic developmental disorder with clinical diversity characterized by hypoparathyroidism, sensorineural deafness and renal disease. Patients usually present with hypocalcaemia, tetany, or afebrile convulsions at any age. Hearing loss is usually bilateral and may range from mild to profound impairment. Renal disease includes nephrotic syndrome, cystic kidney, renal dysplasia, hypoplasia or aplasia, pelvicalyceal deformity, vesicoureteral reflux, chronic kidney disease, hematuria, proteinuria and renal scarring.

The syndrome was originally characterized during 1970 by Mainzer, et al., in a paper published in the American Journal of Medicine. In 1979, Giedion named the syndrome "conorenal syndrome" after a study of eight children. The children had chronic renal failure and the epiphyses of their fingers were cone-shaped and protruded into the metaphysis; some also had retinitis pigmentosa (also called RP, a progressive degeneration of the retina which affects night vision and peripheral vision) or ataxia (an inability to coordinate muscular movements). In 1995, a group led by Mendley studied two siblings and determined that renal histopathologic (features that can be identified in the laboratory) and clinical features of a primarily glomerular disorder (a kidney disorder involving the glomeruli, or clusters of blood vessels that act as filters in the kidney) were features of the syndrome. A recent article by Beals and Weleber (2007) also noted that a majority of patients also have small capital femoral epiphyses (the very tops of the femur where it hits the hip socket ) and/or mild abnormalities of the promixal femoral metaphysis.

The symptoms and/or signs of branchio-oto-renal syndrome are consistent with underdeveloped (hypoplastic) or absent kidneys with resultant renal insufficiency or renal failure. Ear anomalies include extra openings in front of the ears, extra pieces of skin in front of the ears (preauricular tags), or further malformation or absence of the outer ear (pinna). Malformation or absence of the middle ear is also possible, individuals can have mild to profound hearing loss. People with BOR may also have cysts or fistulae along the sides of their neck.

Affected children are developmentally delayed with dwarfism, rickets and osteoporosis. Renal tubular disease is usually present causing aminoaciduria, glycosuria and hypokalemia.

Cysteine deposition is most evident in the conjunctiva and cornea.

This is much more common, but is not usually of any major health consequence, as long as the other kidney is healthy.

It may be associated with an increased incidence of Müllerian duct abnormalities, which are abnormalities of the development of the female reproductive tract and can be a cause of infertility, blocked menstrual flow (hematocolpos), increased need for Caesarean sections, or other problems. Herlyn-Werner-Wunderlich syndrome is one such syndrome in which unilaterial renal agenesis is combined with a blind hemivagina and uterus didelphys. Up to 40% of women with a urogenital tract anomaly also have an associated renal tract anomaly.

Adults with unilateral renal agenesis have considerably higher chances of hypertension (high blood pressure). People with this condition are advised to approach contact sports with caution.

The odds of a person being born with unilateral renal agenesis are approximately 1 in 750.

Inborn errors of renal tubular transport are metabolic disorders which lead to impairment in the ability of solutes, such as salts or amino acids, to be transported across the brush border of the renal tubule. This results in disruptions of renal reabsorption.

Examples of these disorders include Iminoglycinuria, renal tubular acidosis and Gitelman syndrome.

A thorough diagnosis should be performed on every affected individual, and siblings should be studied for deafness, parathyroid and renal disease. The syndrome should be considered in infants who have been diagnosed prenatally with a chromosome 10p defect, and those who have been diagnosed with well defined phenotypes of urinary tract abnormalities. Management consists of treating the clinical abnormalities at the time of presentation. Prognosis depends on the severity of the kidney disease.

Abderhalden–Kaufmann–Lignac syndrome (AKL syndrome), also called Abderhalden–Lignac–Kaufmann disease or nephropathic cystinosis, is an autosomal recessive renal disorder of childhood comprising cystinosis and renal rickets.

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.

Bilateral renal agenesis is a condition in which both kidneys of a fetus fail to develop during gestation. It is one causative agent of Potter sequence. This absence of kidneys causes oligohydramnios, a deficiency of amniotic fluid in a pregnant woman, which can place extra pressure on the developing baby and cause further malformations. The condition is frequently, but not always the result of a genetic disorder, and is more common in infants born to one or more parents with a malformed or absent kidney.

The main consequence of impaired ciliary function is reduced or absent mucus clearance from the lungs, and susceptibility to chronic recurrent respiratory infections, including sinusitis, bronchitis, pneumonia, and otitis media. Progressive damage to the respiratory system is common, including progressive bronchiectasis beginning in early childhood, and sinus disease (sometimes becoming severe in adults). However, diagnosis is often missed early in life despite the characteristic signs and symptoms. In males, immotility of sperm can lead to infertility, although conception remains possible through the use of in vitro fertilization and, as well as this, there have been reported cases where sperm were able to move. Trials have also shown that there is a marked reduction in fertility in female sufferers of Kartagener's Syndrome due to dysfunction of the oviductal cilia.

Many affected individuals experience hearing loss and show symptoms of otitis media which demonstrate variable responsiveness to the insertion of myringotomy tubes or grommets. Some patients have a poor sense of smell, which is believed to accompany high mucus production in the sinuses (although others report normal - or even acute - sensitivity to smell and taste). Clinical progression of the disease is variable, with lung transplantation required in severe cases. Susceptibility to infections can be drastically reduced by an early diagnosis. Treatment with various chest physiotherapy techniques has been observed to reduce the incidence of lung infection and to slow the progression of bronchiectasis dramatically. Aggressive treatment of sinus disease beginning at an early age is believed to slow long-term sinus damage (although this has not yet been adequately documented). Aggressive measures to enhance clearance of mucus, prevent respiratory infections, and treat bacterial superinfections have been observed to slow lung-disease progression. Although the true incidence of the disease is unknown, it is estimated to be 1 in 32,000,

although the actual incidence may be as high as 1 in 15,000.

Marshall JD et al. provided a comprehensive guidance for diagnostic criteria in their 2007 publication.

Birth – 2 years:

Minimum diagnosis requires 2 major criteria or 1 major and 2 minor criteria.

Major criteria are:

1. ALMS1 mutation in 1 allele and/or family history of Alström Syndrome

2. Vision pathology (nystagmus, photophobia).

Minor criteria are:

1. Obesity

2. Dilated cardiomyopathy with congestive heart failure.

Other variable supportive evidence:

Recurrent pulmonary infections, normal digits, delayed developmental milestones.

At 3–14 years of age:

2 major criteria or 1 major and 3 minor criteria.

Major criteria are:

1. ALMS1 mutation in 1 allele and/or family history of Alström Syndrome,

2. Vision pathology (nystagmus, photophobia, diminished acuity). If old enough for testing: cone dystrophy by ERG.

Minor Criteria:

1. Obesity and/or insulin resistance and/or Type 2 Diabetes

2. History of dilated cardiomyopathy with congestive heart failure

3. Hearing loss

4. Hepatic dysfunction

5. Renal failure

6. Advanced bone age

Variable supportive evidence:

Recurrent pulmonary infections, normal digits, delayed developmental milestones, hyperlipidemia, scoliosis, flat wide feet

hypothyroidism, hypertension, recurrent urinary tract infection, growth hormone deficiency.

Presentation 15 years – adulthood:

2 major and 2 minor criteria or 1 major and 4 minor criteria.

Major criteria are:

1) ALMS1 mutation in 1 allele and/or family history of Alström Syndrome.

2) Vision pathology (history of nystagmus in infancy/childhood, legal blindness, cone and rod dystrophy by ERG).

Minor criteria:

1) Obesity and/or insulin resistance and/or Type 2 Diabetes

2) History of dilated cardiomyopathy with congestive heart failure.

3) Hearing loss

4) Hepatic dysfunction

5) Renal failure

6) Short stature

7) Males: hypogonadism, Females: irregular menses and/or hyperandrogenism

Other supportive features:

Recurrent pulmonary infections, normal digits, history of developmental delay, hyperlipidemia, scoliosis, flat wide feet,

hypothyroidism, hypertension, recurrent urinary tract infections/urinary dysfunction, growth hormone deficiency, alopecia.

All people with this disorder have at least one limb abnormality that affects bones in the wrist (carpal bones). Often, these wrist bone abnormalities can be detected only by X-ray. Affected individuals may have additional bone abnormalities that can include polydactyly, a hypoplastic thumb or a Triphalangeal thumb, partial or complete absence of bones in the forearm, an underdeveloped Humerus, and abnormalities that affect the Clavicle and Scapula. Bone abnormalities may affect each arm differently, and the left side can be affected more than the right side. In some cases, only one arm and/or hand is affected.

About 75 percent of individuals with Holt–Oram syndrome have heart problems. The most common problem is a defect in the muscular wall, or septum, that separates the right and left sides of the heart (atria). Atrial septal defects (ASD) are caused by a hole in the septum between the left and right upper chambers of the heart (atria), and ventricular septal defects (VSD) are caused by a hole in the septum between the left and right lower chambers of the heart (ventricles). Sometimes people with Holt–Oram syndrome have cardiac conduction disease, which is caused by abnormalities in the electrical system that coordinates contractions of the heart chambers. Cardiac conduction disease can lead to problems such as a slow heart rate (bradycardia) or a rapid and ineffective contraction of the heart muscles (fibrillation). Cardiac conduction disease can occur along with other heart defects (such as septal defects) or as the only heart problem in people with Holt–Oram syndrome.

Lachiewicz–Sibley syndrome is a rare autosomal dominant disorder characterized by preauricular pits and renal disease. Persons with this disease may have hypoplasic kidneys or proteinuria. This disease was first described in a Caucasian family of British and Irish descent that emigrated to Ohio in the 19th century before settling in Nebraska. Many of the members of this family still live in Nebraska, although the relatives are now scattered throughout the country.

Unlike branchio-oto-renal (BOR) syndrome, Lachiewicz–Sibley syndrome is characterized by only preauricular pitting and renal disease. Persons with BOR syndrome also present with hearing loss, branchial fistulas or cysts, malformed ears, and lacrimal stenosis. Other anomalies in BOR syndrome may include a long narrow face, a deep overbite, and facial paralysis.

It was characterized in 1985.

Branchio-oto-renal syndrome (BOR), also known as branchiootorenal syndrome or BOR syndrome, is an autosomal dominant genetic disorder involving the kidneys, ears, and neck. It often has also been described as Melnick-Fraser syndrome.

The skeletal structures of individuals who have this disorder may have pronounced deformities. As reported by several medical doctors, the following features are commonly found in people who suffer from nail–patella syndrome:

Bones and joints

- Patellar involvement is present in approximately 90% of patients; however, patellar aplasia occurs in only 20%.

- In instances in which the patellae are smaller or luxated, the knees may be unstable.

- The elbows may have limited motion (e.g., limited pronation, supination, extension).

- Subluxation of the radial head may occur.

- Arthrodysplasia of the elbows is reported in approximately 90% of patients.

- General hyperextension of the joints can be present.

- Exostoses arising from the posterior aspect of the iliac bones ("iliac horns") are present in as many as 80% of patients; this finding is considered pathognomonic for the syndrome.

- Other reported bone changes include scoliosis, scapular hypoplasia, and the presence of cervical ribs.

Kidney issues may arise such as proteinuria and nephritis. Proteinuria is usually the first sign of renal involvement and either rapidly or years after suffering from asymptomatic proteinuria, renal failure occurs in around 5% of NPS patients. Hypothyroidism, irritable bowel syndrome, attention deficit hyperactivity disorder (ADHD), and thin tooth enamel are associated with NPS, but whether these are related or simply coincidences are unclear.

When accompanied by the combination of situs inversus (reversal of the internal organs), chronic sinusitis, and bronchiectasis, it is known as Kartagener syndrome (only 50% of primary ciliary dyskinesia cases include situs inversus).

Presenting at birth, features of the disorder include moderately severe IUGR, microcephaly, craniosynostosis, moderately severe post uterine growth retardation, deafness, deep set eyes, cryptorchidism, truncal obesity and acanthosis nigricans, small teeth, prognathism, dislocated radial heads without generalized skeletal dysplasia, however, tall vertebrae, moderate mental retardation, hypothyroidism, insulin resistance, hypoparathyroidism.

RAPADILINO syndrome is an autosomal recessive disorder characterized by:

- RA: radial ray defect

- PA: patellar aplasia, arched or cleft palate

- DI: diarrhea, dislocated joints

- LI: little size (short stature), limb malformation

- NO: nose slender and normal intelligence.

It is more prevalent in Finland than elsewhere in the world.

It has been associated with the gene RECQL4. This is also associated with Rothmund-Thomson syndrome and Baller-Gerold syndrome.

Holt–Oram syndrome (also called Heart and Hand Syndrome, atrio-digital syndrome, atriodigital dysplasia, cardiac-limb syndrome, heart-hand syndrome type 1, HOS, ventriculo-radial syndrome) is an autosomal dominant disorder that affects bones in the arms and hands (the upper limbs) and may also cause heart problems. The syndrome includes an absent radial bone in the arms, an atrial septal defect, and a first degree heart block. Thalidomide syndrome can produce similar morphology to Holt–Oram syndrome, sufficient to be considered a phenocopy.

Birt–Hogg–Dubé syndrome affects the skin and increases the risk of tumors in the kidneys and lungs. The condition is characterized by multiple noncancerous dome-shaped tumors of the hair follicles (fibrofolliculomas), particularly on the face, neck, and—more rarely—the upper chest. The fibrofolliculomas are generally described as having an opaque white color or a yellowish tone and have a waxy, smooth texture. The tumors are always found on and around the nose and on and behind the outer ear. Typically, they first appear in a person's 20s or 30s, and are found in more than 80% of people with the syndrome above the age of 40. The tumors become larger and more numerous over time. Tumors differ between individuals: they may appear merged in plaques, look similar to a comedo with a plug of keratin, or include epidermoid cysts. A large number of tumors on the face can be associated with hyperseborrhea (abnormally elevated sebum production). The presence of fibrofolliculomas on a person's face can cause significant psychological distress.

Other tumors can include trichodiscomas (tumors of the hair disc, which may be identical to fibrofolliculomas), angiofibromas, and perifollicular fibromas. However, angiofibromas are more common in tuberous sclerosis. Along with the tumors, other skin conditions are seen in people with Birt–Hogg–Dubé syndrome. Approximately 40% of people or families with the disease have papules in their mouth, which can be located on the cheeks (buccal mucosa), tongue, gums, or lips. Either white or mucosa-colored, they are discrete, small, and soft and consist of fibrous tissue covered in thickened epithelium. Collagenomas of the skin are also found in some families. Many people with BHD have skin lesions that appear to be acrochordons (skin tags), but may instead be fibrofolliculomas. These lesions are usually found in the armpit, on the eyelids, and in folds of skin. Not all individuals develop the facial tumors; some families with the mutation that causes BHD develop only kidney tumors or spontaneous pneumothorax.

People with the combination of Duane anomaly and radial ray malformations may have a variety of other signs and symptoms. These features include:

- Unusually shaped ears

- Hearing loss

- Heart and kidney defects

- A distinctive facial appearance

- An inward- and downward-turning foot (a clubfoot)

- Fused vertebrae.

Along with fibrofolliculomas and kidney tumors, affected individuals frequently develop cysts (blebs or bullae) in the subpleural lung base or intraparenchymal space that may rupture and cause an abnormal collection of air in the chest cavity (pneumothorax), which could result in the collapse of a lung. The cysts do not cause other symptoms and lung function is usually normal. More than 83% of people with Birt–Hogg–Dubé have cysts, however, the syndrome does not cause conditions like progressive chronic obstructive pulmonary disease (COPD) or generalized respiratory failure, though it does cause emphysema. Spontaneous, sometimes recurrent, pneumothorax occurs far more often and at a younger age with Birt–Hogg–Dubé than in the unaffected population. Approximately 24% of people with the disease suffer at least one spontaneous pneumothorax, 30 times the occurrence in unaffected people. Though pneumothorax caused by Birt–Hogg–Dubé often occurs in middle age, at a median age of 38, 17% of affected people have a spontaneous pneumothorax before turning 40. Pneumothoraces have been seen in people as young as 7 and 16 years of age. Some families have a form of BHD that only affects the lungs.

This is characterized by hand and arm abnormalities. The following are specific characteristics:

- Malformed or absent (aplasia) thumb

- A thumb that looks more like a finger

- Partial or complete absence of a radius

- Shortening and radial deviation of the forearms

- Triphalangeal thumb

- Duplication of the thumb (preaxial polydactyly)