ネイルパテラ症候群（爪膝蓋骨症候群）／ＬＭＸ１Ｂ関連腎症

Nail-patella syndrome (NPS) is an autosomal dominant disorder caused by LMX1B mutations and typically associated with glomerular proteinuria. We report three brothers carrying a maternally inherited heterozygous LMX1B mutation (NM_001174147.2: c.309C > G (p.Cys103Trp)), all presenting with classical skeletal features of NPS. Two siblings developed early-onset proteinuria predominantly composed of low-molecular-weight proteins, hypercalciuria, and ophthalmologic abnormalities including cataracts and glaucoma; one also exhibited nephrocalcinosis. Further genetic analysis identified a hemizygous OCRL pathogenic mutation (NM_000276.4: c.2209G > A (p.Glu737Lys)) in the two affected brothers but not in the third sibling, who had no renal involvement. This intrafamilial discordance supports a dual genetic diagnosis. Our findings emphasize the importance of reconsidering the initial diagnosis when clinical features are atypical and highlight the value of comprehensive genetic testing in patients with unusual renal presentations.

BACKGROUND: Proteinuria is a common manifestation of glomerular disease. Advances in genetic testing have improved recognition of hereditary nephropathies such as LMX1B-associated nephropathy. Coexistence with immune-mediated glomerulonephritis is exceptionally rare. CASE REPORT: We describe a 58-year-old woman with a history of hypertension, type 2 diabetes mellitus, hyperlipidemia, and prior pulmonary embolism who presented with persistent proteinuria. Urinary protein-to-creatinine ratios ranged from 1679 to 3944 mg/g, while renal function remained preserved (estimated GFR 69-103 mL/min/1.73 m²). Genetic testing identified a pathogenic LMX1B mutation consistent with nail-patella syndrome, along with variants of uncertain significance in CYP11B1, ABCC8, and PLG. Kidney biopsy revealed IgA nephropathy with mesangial IgA deposition and ultrastructural findings of podocyte myelinosomes, characteristic of LMX1B-associated nephropathy. Chronicity was minimal (3 of 23 glomeruli globally sclerotic, no segmental sclerosis, and no interstitial fibrosis). Management included renin-angiotensin system blockade and metabolic optimization. CONCLUSION: This case illustrates the diagnostic complexity of dual glomerular pathology and underscores the importance of integrating genetic testing with histopathology in patients with atypical proteinuria.