What are the other Names for this Condition? (Also known as/Symptoms)

• Conorenal Syndrome
• Renal Dysplasia, Retinal Pigmentary Dystrophy, Cerebellar Ataxia, and Skeletal Dysplasia
• Short-Rib Thoracic Dysplasia 9 (SRTD9)

What is Mainzer-Saldino Syndrome? (Definition/Background Information)

• Mainzer-Saldino Syndrome (MSS) is an extremely rare disorder, with a reported prevalence of less than one individual per million populations being affected
• MSS affects the eyes, kidneys, liver, and bones. The age of onset of the disorder is typically during early childhood, and the rate of disorder progression can be variable
• Barring a family history of the disorder, no other risk factors have been described in individual’s being diagnosed with Mainzer-Saldino Syndrome. It is inherited in an autosomal recessive manner
• Mutations in the IFT140 gene are known to cause Mainzer-Saldino Syndrome. The gene codes for a protein that is necessary for the formation of cilia, as well as their maintenance
  • Cilia are microscopic finger-like projections on cells’ surfaces. They are present on the surfaces of liver, kidney, and specialized cells in the eyes that sense light
  • Cilia play a role in signalling pathways, thereby modulating the function of many organs
  • The presence of cilia is necessary for the proper structure and functioning of these organs
• The IFT (intra-flagellar transport) group of proteins help in the transport of substances within the cilia (and related structures known as flagella). The IFT40 gene product is part of a complex of IFT proteins called the IFT-A complex. When the cilia malfunction, the signalling mechanism fails to function properly. This leads to the symptoms of the Mainzer-Saldino Syndrome
• Since cilia are present in multiple organs in the body, the symptoms of the disorder can include malfunctions of several body organs. Abnormality in the bones of the fingers and toes, short stature, permanently fused skull bones, vision problems, kidney malfunction, fibrosis of the liver, problems with gait and balance, and reduced intellectual acuity, are some common symptoms of MSS
• At this time, there are no specific treatments available to cure Mainzer-Saldino Syndrome. Periodic monitoring of the affected individual’s condition and symptomatic treatment are generally necessary. The symptoms that arise in the individual are addressed through the use of corrective glasses for eye problems, dietary restrictions, and dialysis for severe kidney disorder
• The onset and progression of kidney damage is considered key to the survival in individuals with Mainzer-Saldino Syndrome. Early diagnosis and prompt treatment of MSS can help improve one’s quality of life

Who gets Mainzer-Saldino Syndrome? (Age and Sex Distribution)

• Mainzer-Saldino Syndrome is a very rare genetic disorder, with approximately 20 cases being reported in the scientific literature
• The exact prevalence of the disorder is not known. Some reports estimate that the condition affects less than one in every 1,000,000 individuals
• The age of onset of the disorder is typically at 10-14 years of age
• No predilection for any race or ethnicity is known, and both male and female genders are affected

What are the Risk Factors for Mainzer-Saldino Syndrome? (Predisposing Factors)

• Mainzer-Saldino Syndrome is an inherited disorder, and having a family history of the condition is a big risk factor
• Presently, no other risk factors have been identified

It is important to note that having a risk factor does not mean that one will get the condition. A risk factor increases ones chances of getting a condition compared to an individual without the risk factors. Some risk factors are more important than others.

Also, not having a risk factor does not mean that an individual will not get the condition. It is always important to discuss the effect of risk factors with your healthcare provider.

What are the Causes of Mainzer-Saldino Syndrome? (Etiology)

Mainzer-Saldino Syndrome is caused by mutations in the IFT140 gene (IFT stands for intra-flagellar transport). The disorder is inherited in an autosomal recessive manner.

• Under normal circumstances, the IFT140 gene codes for a protein that is necessary for the formation and proper functioning of the cilia
  • Cilia are minute hair-like projections on cell surfaces, and are crucial for the structural integrity of brain, liver, kidney, and bone cells, as well as their functioning
  • Cilia are present on the cells in the retinal that sense light, thereby playing a role in ensuring proper vision
• With other IFT proteins, the IFT40 gene product forms an important component of the IFT-A complex. IFT-A and IFT-B complexes form the IFT particle. The assembly of this complex/particle ensures the transport of molecules within the cilia, so as to enable chemical signalling
• When the IFT140 gene is mutated, the following may be noted:
  • The resultant protein may have an abnormality in shape, function, or in both
  • This may lead to impaired interactions with other IFT proteins, such that the IFT-A complex or the IFT particle is malformed.
  • Consequently, the cilia may not be formed at all, may be few in number or may not be functional. The proper functioning of organs with dysfunctional cilia may be severely affected, leading to the symptoms of the disorder

Note: It is possible that genes other than IFT40, as yet unidentified, are involved in Mainzer-Saldino Syndrome.

Autosomal recessive: Autosomal recessive conditions are traits or disorders that occur when two copies of an abnormal gene have been inherited on a non-sex chromosome. If both parents have an autosomal recessive condition, there is a 100% likelihood of passing on the mutated genes to their children. If, however, only one mutant copy of the gene is inherited, the individual will be a carrier of the condition, but will not be present with any symptoms. Children, born to two carriers, have a 25% chance of being homozygous dominant (unaffected), a 50% chance of being heterozygous (carrier), and a 25% chance of being homozygous recessive (affected). 

What are the Signs and Symptoms of Mainzer-Saldino Syndrome?

The signs and symptoms of Mainzer-Saldino Syndrome may involve many organs and systems, which are described below:

• Skeletal system signs and symptoms include:
  • Abnormal cone-shaped development of rounded ends of bones (epiphyses)
  • Short fingers
  • Abnormal thigh bone development
  • Microcephaly (abnormal shape/size of the head), owing to fusion of skull bones that can occur prematurely
  • Short stature
  • Short rib bones and consequent breathing problems and higher susceptibility to infections
• Eye signs and symptoms include:
  • Nystagmus, or involuntary and rapid movement of eyes, blurred vision
  • Tunnel vision, impaired vision at night or in reduced light conditions (retinitis pigmentosa)
  • Cross-eyes
  • Progressive loss of vision acuity
  • Retinal detachment
• Brain signs and symptoms include:
  • Lack of coordination in movement
  • Problems with balance
  • Compromised intellect, generally mild
• Liver signs and symptoms include:
  • Swelling/enlargement of the organ
  • Scar tissue formation (fibrosis)
• Kidney signs and symptoms include:
  • Presence of blood/protein in urine
  • Increased risk of urinary tract infections
  • Progressive organ malfunction
  • Kidney failure
• Anemia
• Hyperkalemia - increase in levels of potassium in blood

How is Mainzer-Saldino Syndrome Diagnosed?

Mainzer-Saldino Syndrome is diagnosed with the help of the following tools:

• Complete physical examination and assessment of symptoms
• Evaluation and analysis of family medical history
• Imaging tests such as X-ray, for checking bone abnormalities in the face, skull, fingers and long bones
• Blood tests for general, kidney and liver health
• Urine tests to check for the following:
  • Blood
  • Protein
  • Volume of urine
  • Infections in the urinary tract
• Eye exams to check for the following:
  • Vision acuity
  • Structural changes in retina
  • Damage to retina

Many clinical conditions may have similar signs and symptoms. Your healthcare provider may perform additional tests to rule out other clinical conditions to arrive at a definitive diagnosis.

What are the possible Complications of Mainzer-Saldino Syndrome?

The following are some potential complications of Mainzer-Saldino Syndrome:

• Inflammation and scarring of kidney tissue (fibrosis); a condition known as nephronophthisis
• Formation of cysts in the kidney
• Progressive kidney dysfunction, kidney failure, and end-stage kidney disorder
• Fibrosis of the liver
• Liver enlargement
• Erratic heartbeats due to untreated hyperkalemia

How is Mainzer-Saldino Syndrome Treated?

Since Mainzer-Saldino Syndrome has a genetic basis, the disorder is not curable. However, a timely diagnosis and symptomatic treatment can improve the quality of life of those affected.

The following are some symptomatic treatment options available:

• Corrective lenses for vision problems
• Medication to improve hemoglobin (such as iron tablets) for anemia
• Medication (such as calcium) to treat hyperkalemia
• Antibiotics for urinary tract infections
• Dialysis for kidney failure
• Renal transplantation for kidney failure or end-stage renal disorder

MSS is a very rare disorder; research is currently ongoing to understand and combat the disorder with varied treatment options.

How can Mainzer-Saldino Syndrome be Prevented?

• Currently, there are no specific methods or guidelines to prevent Mainzer-Saldino Syndrome, since it is a genetic condition
• Genetic testing of the expecting parents (and related family members) and prenatal diagnosis (molecular testing of the fetus during pregnancy) may help in understanding the risks better during pregnancy
• If there is a family history of the condition, then genetic counseling will help assess risks, before planning for a child
• Active research is currently being performed to explore the possibilities for treatment and prevention of inherited and acquired genetic disorders such as Mainzer-Saldino Syndrome

Regular medical screening at periodic intervals with tests and physical examinations are highly recommended.

What is the Prognosis of Mainzer-Saldino Syndrome? (Outcomes/Resolutions)

• The prognosis of Mainzer-Saldino Syndrome mainly depends on the severity of kidney dysfunction
• Kidney transplantation as treatment for failure of the organ is reported to reduce the incidence of fatalities due to MSS
• Since there is no cure for this disorder, providing symptomatic treatment is considered the best course of action

Additional and Relevant Useful Information for Mainzer-Saldino Syndrome:

• Ciliopathies is an emerging class of genetic disorders due to altered cilia assembly, maintenance, or function
  • Syndromic ciliopathies affecting bone development have been classified as skeletal ciliopathies
  • Mutations in genes encoding components of the intraflagellar transport (IFT) complex A, that drives retrograde ciliary transport, are a major cause of skeletal ciliopathies.
• Mainzer-Saldino Syndrome (MSS) is a rare disorder characterized by phalangeal cone-shaped epiphyses, chronic renal failure and early-onset severe retinal dystrophy. After Sensenbrenner and Jeune syndromes, MSS is the ultimate skeletal ciliopathy ascribed to IFT disorganization