Senior–Løken syndrome

The worldwide prevalence is estimated at around 1/1,000,000.

Senior-Loken syndrome is inherited in an autosomal recessive manner. Parents of an affected individual are typically heterozygous carriers, and the recurrence risk for each subsequent pregnancy of two carrier parents is 25%. Prenatal molecular testing is technically possible once the familial pathogenic variants have been identified.

Main differential diagnoses include:

• : cerebellar and brain-stem malformation (molar tooth sign on MRI), hypotonia, developmental delay, and abnormal breathing/eye movements; CEP290, AHI1, TMEM67, and others
• : retinal dystrophy with obesity, postaxial polydactyly, cognitive impairment, and variable kidney involvement; BBS1, BBS10, and others
• : retinal dystrophy with sensorineural hearing loss, dilated cardiomyopathy, childhood obesity, insulin resistance, and progressive kidney disease (no polydactyly or developmental delay); ALMS1

• Establishing or confirming the molecular diagnosis at the level of the underlying gene and variant.
• Identifying the underlying genetic cause enables specific and individualised surveillance of disease progression and clinical management.
• Once the familial pathogenic variants are known, predictive testing of at-risk family members can be considered after genetic counselling.

• Stokman M, Lilien M, Knoers N. Nephronophthisis-related ciliopathies. In: Adam MP, Feldman J, Mirzaa GM, Pagon RA, Wallace SE, Bean LJH, Gripp KW, Amemiya A, editors. GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993–. Updated 2023 Mar 2. Available from: https://www.ncbi.nlm.nih.gov/books/NBK368475/. PMID: .
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• Leggatt GP, Seaby EG, Veighey K, Gast C, Gilbert RD, Ennis S. A role for genetic modifiers in tubulointerstitial kidney diseases. Genes (Basel). 2023;14(8):1582. doi:10.3390/genes14081582. PMID: ; PMCID: PMC10454709.
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