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Mainzer-Saldino syndrome
This syndrome is a type of ciliopathy, meaning it arises from problems with cellular structures called cilia. It can lead to kidney disease, skeletal abnormalities, and visual impairment, typically presenting in childhood.
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Overview
Mainzer-Saldino syndrome is a rare inherited disorder classified as a ciliopathy. Cilia are tiny, hair-like structures found on the surface of most cells in the body, playing crucial roles in cell communication and various organ functions. When cilia do not function correctly, it can lead to a range of health issues in different body systems, which is characteristic of ciliopathies [PMID:24771217].
Individuals with Mainzer-Saldino syndrome typically experience problems affecting the kidneys, skeletal system, and eyes. The severity of these features can vary between affected individuals. It is considered a rare condition, though the exact number of people affected is not well established.
Symptoms & clinical features
The symptoms of Mainzer-Saldino syndrome often become apparent during childhood. Kidney involvement is a key feature, commonly presenting as chronic kidney disease. This can progress over time, sometimes leading to kidney failure [PMID:22037002].
Skeletal abnormalities are also common. These can include short stature, cone-shaped epiphyses (the ends of long bones), and short fingers and toes. Some individuals may also have a narrow chest. Eye problems can range from retinal degeneration, which affects vision, to nystagmus (involuntary eye movements) [PMID:22037002]. Liver involvement, such as hepatic fibrosis, has also been reported in some cases, contributing to the varied presentation of the syndrome.
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Affected organs
The primary organs affected in Mainzer-Saldino syndrome are the kidneys, leading to progressive kidney disease. The skeletal system is also significantly impacted, resulting in various bone abnormalities, particularly affecting long bones, hands, and feet.
The eyes are frequently affected, with potential for retinal degeneration causing visual impairment. In some instances, the liver may also be involved, showing signs of fibrosis. These diverse effects underscore the systemic nature of ciliopathies.
Risks & severity
Mainzer-Saldino syndrome presents with a spectrum of severity; however, it is generally considered a severe condition. The risk of developing chronic kidney disease is high, often progressing to end-stage renal disease, which may require dialysis or kidney transplantation, sometimes even in childhood. The skeletal changes can contribute to short stature and impact mobility.
Visual impairment due to retinal degeneration is a significant concern, which can worsen over time. The age of onset for symptoms is typically in infancy or early childhood, although the progression and specific health challenges can differ between individuals. Regular monitoring is essential to manage potential complications.
Genetic causes
Mainzer-Saldino syndrome is caused by pathogenic variants in specific genes that are vital for the proper function of cilia. The two main genes implicated are IFT140 and IFT172 [PMID:27986068].
The IFT140 gene provides instructions for making a protein called intraflagellar transport 140. This protein is a crucial component of the intraflagellar transport (IFT) system, which is responsible for building and maintaining cilia. Similarly, the IFT172 gene produces a protein also involved in the IFT process. Pathogenic variants in these genes disrupt the normal formation and function of cilia, leading to the diverse symptoms seen in Mainzer-Saldino syndrome.
Inheritance pattern
Mainzer-Saldino syndrome has an autosomal recessive pattern of inheritance. This means that an individual must inherit two pathogenic variants, one from each parent, to develop the condition.
Parents who each carry one pathogenic variant (they are 'carriers') typically do not show symptoms of the syndrome themselves. However, for each pregnancy, there is a 25% chance that their child will inherit two pathogenic variants and develop Mainzer-Saldino syndrome. There is a 50% chance the child will be a carrier like their parents, and a 25% chance the child will inherit two normal copies of the gene.
When both parents are carriers, each child has a 25% chance of being affected, 50% of being a carrier, and 25% of being unaffected.
Diagnosis & testing
Diagnosis of Mainzer-Saldino syndrome typically begins with a clinical suspicion based on the presence of characteristic symptoms, such as kidney disease, skeletal abnormalities, and visual problems. Imaging studies like X-rays can help identify skeletal features, and renal ultrasounds can assess kidney health.
Confirmation of the diagnosis is made through genetic testing. This involves analysing the IFT140 and IFT172 genes to identify pathogenic variants. In the UK, genetic testing for ciliopathies is available through the NHS Genomic Medicine Service (GMS), often initiated by specialist clinicians like paediatric nephrologists or clinical geneticists, under relevant R-codes.
Management & lifestyle
Management for Mainzer-Saldino syndrome is supportive and aims to address the specific symptoms and complications experienced by each individual. This typically involves a multidisciplinary team of specialists, including nephrologists for kidney care, orthopaedic surgeons for skeletal issues, and ophthalmologists for vision problems. Regular monitoring of kidney function is crucial, and interventions such as medication to manage kidney disease, dietary adjustments, or in advanced cases, dialysis or kidney transplantation, may be required.
Skeletal abnormalities may be managed with orthopaedic interventions if necessary. Ocular examinations are important to monitor for retinal degeneration and support vision as needed. Genetic counsellors can provide essential information about the condition, its inheritance pattern, and family planning options.
UK care pathway
In the UK, individuals suspected of having genetic conditions like Mainzer-Saldino syndrome are often referred to specialist services within the NHS Genomic Medicine Service (GMS). This typically involves a referral to a clinical genetics team or a specialist consultant (e.g., paediatric nephrologist). Genetic counsellors play a key role in explaining the condition, inheritance patterns, and the implications of genetic testing. Genetic testing for this condition would fall under specific R-codes for renal ciliopathies or syndromic kidney disease, allowing for comprehensive genomic analysis.
Frequently asked questions
What are cilia and why are they important?
Cilia are microscopic, hair-like structures found on almost every cell in the human body. They act as cellular antennae, sensing the environment and facilitating communication between cells, which is essential for the proper development and function of many organs, including the kidneys, eyes, and bones.
How serious is Mainzer-Saldino syndrome?
Mainzer-Saldino syndrome is generally considered a serious condition because it can lead to significant health problems, particularly progressive kidney disease that may require dialysis or transplantation. The severity can vary, but lifelong medical management and monitoring are typically necessary.
Can Mainzer-Saldino syndrome be cured?
There is currently no cure for Mainzer-Saldino syndrome. Management focuses on treating the symptoms and complications to improve quality of life. This includes medical interventions for kidney disease, orthopaedic care, and support for visual impairment.
If I have Mainzer-Saldino syndrome, what does this mean for my children?
Mainzer-Saldino syndrome is inherited in an autosomal recessive manner. If you have the syndrome, it means you have two pathogenic variants. For your children to be affected, your partner would also need to be a carrier of a pathogenic variant in one of the relevant genes. Genetic counselling can provide personalised risk assessments and discuss reproductive options.
Where can I find support for Mainzer-Saldino syndrome?
In the UK, your clinical genetics team or specialist doctor can signpost you to relevant support groups and patient organisations for rare kidney diseases or ciliopathies. Connecting with these groups can provide valuable peer support and information.
References
- Karuntu JS, Almushattat H, Nguyen XT. Syndromic retinitis pigmentosa. Progress in retinal and eye research. 2025. PMID: 39733931
- König J, Kranz B, König S. Phenotypic Spectrum of Children with Nephronophthisis and Related Ciliopathies. Clinical journal of the American Society of Nephrology : CJASN. 2017. PMID: 29146700
- Montolío-Marzo S, Català-Mora J, Madrid-Aris Á. IFT144 and mild retinitis pigmentosa in Mainzer-Saldino syndrome: A new association. European journal of medical genetics. 2020. PMID: 33002628
- Zheng NX, Miao YT, Zhang X. Primary cilia-associated protein IFT172 in ciliopathies. Frontiers in cell and developmental biology. 2023. PMID: 36733456
- Marhoon SE, Ali AH, Husain A. IFT140 Mutation and End-Stage Renal Disease in Mainzer-Saldino Syndrome: A Case Report. Cureus. 2024. PMID: 38465144
- Oud MM, Latour BL, Bakey Z. Cellular ciliary phenotyping indicates pathogenicity of novel variants in IFT140 and confirms a Mainzer-Saldino syndrome diagnosis. Cilia. 2018. PMID: 30479745
- Cevik S, Zhao P, Zorluer A. Matching variants for functional characterization of genetic variants. G3 (Bethesda, Md.). 2023. PMID: 37933433
- Perrault I, Saunier S, Hanein S. Mainzer-Saldino syndrome is a ciliopathy caused by IFT140 mutations. American journal of human genetics. 2012. PMID: 22503633