Conorenal syndrome

Overview

Conorenal syndrome, also known as Mainzer-Saldino syndrome, is a rare inherited disorder that affects the development and function of multiple organ systems, most notably the kidneys and skeletal system. It is considered a type of ciliopathy—a disorder caused by defective cilia, which are tiny, hair-like structures on the surface of cells that play a key role in signaling and development. Individuals with conorenal syndrome typically present with chronic kidney disease and skeletal abnormalities, often accompanied by vision problems and, in some cases, intellectual disability.

Causes

Conorenal syndrome is caused by mutations in genes that are involved in the structure and function of primary cilia. Several genes have been implicated, including:

• IFT140

• TTC21B

• WDR19

These mutations impair cilia formation and function, disrupting cell signaling pathways essential for kidney development, skeletal patterning, and retinal function. The condition is inherited in an autosomal recessive pattern, meaning both parents must carry a copy of the mutated gene for their child to be affected.

Symptoms

The symptoms of conorenal syndrome can vary in severity but generally include a combination of the following:

• Kidney disease: Chronic kidney disease (CKD) or nephronophthisis, leading to progressive kidney failure

• Skeletal abnormalities: Cone-shaped epiphyses, short stature, shortened or bowed limbs

• Ocular defects: Retinal dystrophy, nystagmus, or progressive vision loss (in some patients)

• Intellectual disability: Present in some cases but not universal

• Facial dysmorphism: Subtle craniofacial abnormalities may be present in certain individuals

• Polydactyly: Extra fingers or toes (rare)

Symptoms usually begin in early childhood and may progress over time, particularly with respect to kidney and visual function.

Diagnosis

Diagnosis of conorenal syndrome involves a combination of clinical, radiological, and genetic evaluations. Diagnostic steps include:

• Clinical examination: Assessment of growth, skeletal anomalies, and kidney-related symptoms

• Renal ultrasound: May show echogenic kidneys, corticomedullary cysts, or signs of nephronophthisis

• X-rays: To identify cone-shaped epiphyses and other skeletal deformities

• Ophthalmologic evaluation: To detect retinal dystrophy or other vision-related issues

• Genetic testing: To identify mutations in IFT140, TTC21B, or WDR19 and confirm the diagnosis

• Family history assessment: Important for evaluating recurrence risk and carrier status

Treatment

There is no cure for conorenal syndrome, so treatment is supportive and aimed at managing symptoms and preventing complications. A multidisciplinary approach is typically required. Treatment strategies include:

• Nephrology care: Regular monitoring of kidney function and blood pressure; dialysis or kidney transplantation may be necessary in advanced cases

• Orthopedic management: Physical therapy, orthopedic surgery, or bracing for skeletal deformities

• Vision support: Regular eye exams, corrective lenses, and low vision aids

• Developmental and educational support: For children with learning or developmental delays

• Genetic counseling: For affected families to understand inheritance patterns and reproductive options

Prognosis

The prognosis of conorenal syndrome varies depending on the severity of kidney involvement and associated complications. Many individuals will develop end-stage renal disease (ESRD) in childhood or adolescence, requiring dialysis or kidney transplantation. Skeletal and visual impairments can affect mobility and independence, but with proper management, many patients can achieve a good quality of life. Early diagnosis, coordinated care, and long-term follow-up are essential for optimizing outcomes.