A Possible Correlation between Nephronophthisis and Glaucoma

Introduction: Cilia perceive extracellular signals like growth factors, chemicals and light for normal kidney development and maintenance. 'Ciliopathies' are autosomal recessive genetic diseases caused by their dysfunction. Most commonly affected are the kidneys causing Nephronophthisis (NPH), but the brain, eye, face, liver, heart and skeleton are also involved. Several associations between NPH and other conditions have been discovered. This case report describes an unusual combination of glaucoma and NPH leading to profound visual and renal function loss. Case Description: A 20-year-old African American male presented with progressive vision loss after undergoing retinal cryotherapy and laser at the age of 4 for an unknown retinopathy. He had end-stage renal disease (ESRD) secondary to infantile NPH confirmed by genetic testing, having already failed transplantation twice. Eye examination noted decreased visual acuity bilaterally with only preserved light perception; he also had horizontal nystagmus, elevated intraocular pressure, retinal dystrophy and optic atrophy. Despite the discontinuation of steroids after the failure of his second allograft, tonometry continued to suggest open-angle glaucoma, concerning for a different disease process. Discussion: Over 90 gene mutations are involved in ciliopathies, of which more than 20 give rise to NPH. NPH has 3 forms – infantile, juvenile and adult; while the latter two produce tubulointerstitial fibrosis, infantile NPH causes a more severe medullary cystic kidney disease that quickly progresses to ESRD. Retinopathy in conjunction with NPH, is a rare autosomal recessive disease affecting 1 in a million, called Senior-Loken syndrome that presents with childhood-onset hyperopia, photophobia and nystagmus. Glaucoma has been recognized in other ciliopathies. In this case, despite the estimated 3% risk of permanent glaucoma following steroid cessation, dysfunctional cilia impairing aqueous humor outflow in the anterior segment of the eye may be responsible. Life expectancy with NPH may vary depending on the onset of ESRD. Although renal transplantation is the only solution currently, specific signaling pathways like cAMP/PKA, mTOR and Hedgehog are potential sites for therapy. Identification of patients with NPH and new associations adds to the literature and maximizes pathological discoveries, thus paving the way for better treatment.