Steroid-Resistant Nephrotic Syndrome and Chronic Kidney Disease Associated with 6p Duplication Syndrome: A Case Report

Introduction

Focal segmental glomerulosclerosis (FSGS) is a glomerulopathy causing nephrotic-range proteinuria, hypoalbuminemia, progressive renal dysfunction, and is a major cause of nephrotic syndrome in adolescents and adults. It results from podocyte injury and may be primary, secondary, or genetic. In childhood steroid-resistant nephrotic syndrome (SRNS), genetic causes are common.¹

6p duplication syndrome is a rare chromosomal disorder with variable features, including developmental delay, craniofacial anomalies, and occasional renal involvement. We report a case of SRNS with FSGS and CKD associated with a 6p25.4q35 duplication, highlighting the role of genetic testing in nephrology.

Case Report

A 14-year-old female with obesity, impaired glucose tolerance, hyperlipidemia, and developmental delay was referred to pediatric nephrology for elevated serum creatinine and hypoalbuminemia. Family history showed no consanguinity, but a brother with similar findings had died at age 20. Labs revealed creatinine 1.31 mg/dL, albumin 2.9 g/dL, and a urine protein/creatinine ratio of 5 mg/mg, with normal complement levels. She was diagnosed with nephrotic syndrome and started on corticosteroids. After 4 weeks without remission, she was classified as SRNS and treated with a calcineurin inhibitor. Renal biopsy showed FSGS. Due to SRNS with intellectual disability, craniofacial anomalies, limb abnormalities, obesity, and skeletal deformities, genetic testing was performed, revealing a 6p25.4q35 duplication. The patient’s family received genetic counseling from our hospital’s genetics department; family screening was not recommended in accordance with national health policy. Despite immunosuppressive therapy, no response was seen after 6 months, so treatment was discontinued. She was maintained on angiotensin-converting enzyme (ACE) inhibitors and supportive CKD management.

Discussion

6p duplication syndrome is a rare chromosomal disorder with a broad phenotypic spectrum.² Most reported cases involve deletions or translocations rather than isolated duplications, leading to multisystem involvement and clinical variability.³ The patient in this report exhibited features consistent with previously described 6p duplication phenotypes, including obesity, intellectual disability, skeletal anomalies, hemifacial asymmetry and insulin resistance.⁴ Renal findings in the literature are usually limited to structural anomalies within the congenital anomalies of the kidney and urinary tract (CAKUT) spectrum, while glomerular involvement such as FSGS is rarely described.⁵ Previously reported renal and extrarenal findings in patients with 6p duplication syndrome are summarized in Table 1.

In this case, progressive proteinuria and renal dysfunction led to biopsy-proven FSGS and genetic analysis identified a 6p25.4q35 duplication. Genes within this region: FOXC1, IRF4, RREB1, and SERPINB, play crucial roles in kidney development and function.⁶ FOXC1, a transcription factor active during renal and urinary tract development, has been associated with both CAKUT and glomerular disease when dysregulated.⁴ Therefore, the FSGS observed in this patient may be attributable to FOXC1 duplication. A similar clinical picture in the patient’s deceased brother suggests possible familial inheritance, though parental testing was unavailable.

This case expands the renal spectrum of 6p duplication syndrome by linking it to FSGS and CKD. Before genetic testing, the patient’s multisystem findings were approached as separate conditions; molecular diagnosis provided a unified explanation. Genetic analysis should be considered in children with SRNS and multisystemic features, as it guides diagnosis, management, and prognosis, underscoring the need for multidisciplinary evaluation.