Serpentine fibula-polycystic kidney syndrome

Overview

Serpentine fibula–polycystic kidney syndrome (SFPKS) is a very rare genetic disorder that affects skeletal development and kidney function. It is characterized by congenital limb anomalies—most notably the presence of a "serpentine" or bowed fibula bone—and bilateral polycystic kidneys. First described in the early 2000s, SFPKS has since been identified as part of the spectrum of ciliopathies—genetic conditions caused by defects in the structure or function of cilia, which are hair-like structures involved in cellular signaling and development. The syndrome typically presents at birth or in early infancy, with varying severity among affected individuals.

Causes

SFPKS is caused by mutations in the NEK8 gene, which encodes a protein involved in ciliary function and cell cycle regulation. NEK8 is expressed in both the kidneys and developing skeleton, and mutations lead to structural anomalies in these systems. The disorder is inherited in an autosomal recessive manner, meaning that an individual must inherit two defective copies of the gene (one from each parent) to develop the syndrome. Parents who carry one copy of the mutated gene are typically asymptomatic carriers.

Symptoms

Serpentine fibula–polycystic kidney syndrome manifests with a variety of skeletal and renal abnormalities, which can range from mild to severe. Common symptoms include:

Skeletal Abnormalities:

• Bowed fibula bones (serpentine or S-shaped appearance)

• Limb length discrepancy or short stature

• Other long bone deformities, including radius and ulna abnormalities

• Joint laxity or contractures

• Facial dysmorphisms in some cases (e.g., midface hypoplasia)

Renal Abnormalities:

• Bilateral polycystic kidneys (multiple cysts in both kidneys)

• Progressive kidney enlargement

• Hypertension (high blood pressure)

• Proteinuria or hematuria (protein or blood in urine)

• Chronic kidney disease or early-onset renal failure

Other Features:

• Occasional hepatic (liver) fibrosis

• Growth retardation

• Variable developmental delays in severe cases

The severity of symptoms can differ widely between individuals, even among those with the same genetic mutation.

Diagnosis

Diagnosis of SFPKS involves a combination of clinical evaluation, imaging studies, and genetic testing. Key diagnostic steps include:

• Physical examination: Identification of limb abnormalities and growth delays

• X-rays or skeletal survey: To confirm the presence of serpentine fibula and other bone deformities

• Renal ultrasound or MRI: To detect bilateral polycystic kidneys and monitor kidney size and structure

• Renal function tests: Including serum creatinine, blood urea nitrogen (BUN), and urinalysis

• Genetic testing: Confirmation through identification of biallelic pathogenic variants in the NEK8 gene

Differentiation from other disorders such as Jeune syndrome, Sensenbrenner syndrome, and autosomal recessive polycystic kidney disease (ARPKD) is essential for accurate diagnosis and management.

Treatment

There is no cure for SFPKS, and treatment focuses on managing symptoms and preventing complications. A multidisciplinary team including pediatric nephrologists, orthopedic surgeons, geneticists, and physical therapists is typically involved.

Renal Management:

• Regular monitoring of kidney function and blood pressure

• Management of hypertension with medications

• Dietary modifications and fluid management as recommended by a nephrologist

• Dialysis or kidney transplantation in cases of end-stage renal disease

Skeletal and Orthopedic Care:

• Orthopedic surgery to correct limb deformities or improve mobility

• Physical therapy to support motor development and joint function

• Orthotic devices for limb support

Supportive Therapies:

• Growth monitoring and nutritional support

• Psychological support and family counseling

• Genetic counseling for families

Prognosis

The prognosis for individuals with SFPKS depends largely on the severity of kidney involvement and the success of orthopedic interventions. Children with mild to moderate symptoms can live into adulthood with appropriate medical management and may achieve a good quality of life. However, those with severe renal impairment may require early dialysis or kidney transplantation. The progression of kidney disease varies, and regular follow-up is essential for monitoring and intervention.

Early diagnosis, genetic counseling, and a comprehensive, team-based care plan are critical for optimizing outcomes and supporting affected individuals and their families throughout their lives.