Expanding the Senior-Løken syndrome spectrum: Combined Rothmund-Thomson features unveil the distinct Teelwani Syndrome phenotype

Background : Senior-Løken Syndrome (SLSN) is a rare autosomal recessive typically ciliopathy characterized by nephronophthisis and retinal dystrophy. Nephronophthisis, a leading genetic cause of chronic kidney disease (CKD) in children and young adults, is characterized by progressive tubulointerstitial fibrosis, tubular atrophy, and cyst formation, ultimately leading to end-stage renal disease (ESRD). Retinal dystrophy in SLS manifests as either Leber congenital amaurosis or late-onset pigmentary retinopathy, resulting in progressive visual impairment Case Summary : This case presents an atypical phenotype of SLSN due to a NPHP4 mutation, with additional multisystem involvement suggestive of a broader ciliopathy spectrum or a novel syndromic overlap.We report a 22-year-old male with genetically confirmed SLSN4, manifesting early-onset cataracts, proximal renal tubular acidosis (RTA) and progressive chronic kidney disease (CKD) However, his phenotype extends beyond the classical presentation, encompassing cryptorchidism, empty sella, cicatricial alopecia, webbed toes, and pancytopenia, which are not traditionally associated with NPHP4 mutations. Genetic analysis identified a coexisting homozygous RECQL4 variant, raising the possibility of a syndromic overlap with Rothmund-Thomson Syndrome type 2 (RTS2). This expands the understanding of ciliopathies and their variable expressivity.The unique combination of renal, endocrine, dermatologic, and skeletal abnormalities suggests either digenic inheritance or an unidentified genetic interaction contributing to this rare phenotype. The presence of an empty sella, an uncommon finding in SLSN, further suggests a possible ciliopathy-related pituitary dysfunction. Given the absence of a clear genotype-phenotype correlation, this case underscores the need for expanded genetic analysis, whole-genome sequencing, and functional studies to delineate the molecular mechanisms underlying this presentation. Conclusion : This case highlights a rare and complex presentation of SLSN4, emphasizing the expanding phenotypic spectrum of ciliopathies and the potential role of additional genetic modifiers. It warrants further investigation into digenic inheritance and novel ciliopathy-related pathways. This report is crucial for refining diagnostic algorithms and multidisciplinary management strategies in rare genetic syndromes.