Perceived family impact and coping mechanisms of caregivers of children with nephrotic syndrome.

BACKGROUND: Pediatric chronic disease impacts the affected child and their family structure. There is limited literature investigating the psychosocial impact of nephrotic syndrome on families. METHODS: Caregivers of children with nephrotic syndrome completed two validated surveys: (1) Impact on Family (IOF) that evaluates the family impact (degree to which family is affected by a pediatric chronic illness) and (2) Coping Health Inventory for Parents (CHIP) that examines the coping patterns used by caregivers. Linear regression models were utilized to determine predictors of perceived family impact and coping patterns. RESULTS: Seventy-five caregivers of a child with nephrotic syndrome completed the surveys. On a scale from low impact to significant impact to very serious impact, results indicated that nephrotic syndrome had a significant impact on families (mean revised IOF total score 33.04 ± 9.38). Families in the steroid-resistant nephrotic syndrome (SRNS) group reported a higher financial impact compared to the steroid-sensitive nephrotic syndrome (SSNS) group (p = 0.03). Families in the frequently relapsing group (FRNS) reported a higher impact on the caregiver's ability to cope with the child's condition compared to the SRNS group (p = 0.02). Tacrolimus use was associated with increasing the perceived family impact (ß = 4.76, p = 0.046). CHIP scores indicated that caregivers did not cope well with family integration (component I) but coped well with social support (component II) and communication (component III). CONCLUSIONS: Childhood nephrotic syndrome has a significant overall perceived impact on the family, and caregivers did not cope well regarding strengthening their family life. These findings can be used as outcome measures for future intervention studies to find solutions that would decrease the perceived family burden. A higher resolution version of the Graphical abstract is available as Supplementary information.

COL4A4 variant recently identified: lessons learned in variant interpretation-a case report.

BACKGROUND: Alport syndrome is a hereditary kidney disease characterized by hematuria and proteinuria. Although there have been reports of autosomal dominant COL4A4 variants, this is likely an underdiagnosed condition. Improved access to affordable genetic testing has increased the diagnosis of Alport syndrome. As genetic testing becomes ubiquitous, it is imperative that clinical nephrologists understand the benefits and challenges associated with clinical genetic testing. CASE PRESENTATION: We present a family of Mexican descent with a heterozygous COL4A4 variant (c.5007delC, ClinVar accession numbers: SCV001580980.2, SCV001993731.1) not previously discussed in detail in the literature. The proband received a biopsy diagnosis suggestive of Fabry disease 18 years after she first developed hematuria and progressed to chronic kidney disease stage III. One year later, the proband was provisionally diagnosed with Alport syndrome after a variant of uncertain significance in the COL4A4 gene was identified following targeted family variant testing of her daughter. Upon review of the medical histories of the proband's children and niece, all but one had the same variant. Of the four with the variant, three display clinical symptoms of hematuria, and/or proteinuria. The youngest of the four, only months old, has yet to exhibit clinical symptoms. Despite these findings there was a considerable delay in synthesizing this data, as patients were tested in different commercial genetic testing laboratories. Subsequently, understanding this family's inheritance pattern, family history, and clinical symptoms, as well as the location of the COL4A4 variant resulted in the upgrade of the variant's classification. Although the classification of this variant varied among different clinical genetic testing laboratories, the consensus was that this variant is likely pathogenic. CONCLUSIONS: This COL4A4 variant (c.5007delC) not yet discussed in detail in the literature is associated with Alport syndrome. The inheritance pattern is suggestive of autosomal dominant inheritance. This report highlights the intricacies of variant interpretation and classification, the siloed nature of commercial genetic testing laboratories, and the importance of a thorough family history for proper variant interpretation. Additionally, the cases demonstrate the varied clinical presentations of Alport syndrome and suggest the utility of early screening, diagnosis, monitoring, and treatment.