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

Expanding the Senior-Løken syndrome spectrum: Combined Rothmund-Thomson features unveil the distinct Teelwani Syndrome phenotype | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Case Report Expanding the Senior-Løken syndrome spectrum: Combined Rothmund-Thomson features unveil the distinct Teelwani Syndrome phenotype Mehraj ul islam, Muzafar Maqsood Wani, Amir Farooq, Imtiyaz Ahmad Wani, and 1 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-7432684/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract 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. Urology & Nephrology Molecular Genetics Senior-Løken syndrome Nephronophthisis Ciliopathy Nephrogenic diabetes insipidus Teelwani Syndrome Figures Figure 1 Figure 2 Introduction Senior-Løken syndrome (SLS) is a rare autosomal recessive disorder characterized by the coexistence of nephronophthisis (NPH) and retinal dystrophy, both resulting from defects in primary cilia function [ 1 ]. 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 presents as either Leber congenital amaurosis or late-onset pigmentary retinopathy, causing progressive visual impairment. The estimated prevalence of SLS is approximately 1 in 50,000 live births, accounting for 10–15% of NPH cases [ 2 ]. While the renal-retinal phenotype is well established, reports of additional systemic involvement - including skeletal abnormalities, endocrine dysfunction, and neurological deficits - suggest a broader ciliopathy spectrum [ 2 ]. We report a genetically confirmed case of SLS with several uncommon features, including proximal renal tubular acidosis (RTA), cryptorchidism, empty sella syndrome, intellectual disability, and skeletal anomalies such as webbed toes and mallet toes. These findings expand the phenotypic spectrum of SLS and underscore the need for comprehensive evaluation in patients with suspected ciliopathies. This case highlights the importance of recognizing atypical manifestations, which may have implications for early diagnosis, genetic counseling, and long-term management. Case Presentation We report the case of a 22-year-old male, born of a consanguineous marriage, who had progressive polyuria and polydipsia since infancy, leading to a diagnosis of nephrogenic diabetes insipidus (NDI) at the age of 16. His symptoms were first noticed in infancy, with excessive diaper wetting, persistent bedwetting, and an unusually high fluid intake, which continued into adolescence. A water deprivation test confirmed NDI, and a pituitary MRI revealed an absent posterior pituitary bright spot with optic nerve tortuosity. He was initially started on desmopressin and later switched to thiazide diuretics for better symptom control. In addition to NDI, he had a history of bilateral developmental cataracts identified at the age of nine due to poor vision and whitish pupillary reflexes. He underwent bilateral cataract extraction with posterior chamber intraocular lens placement and now has corrected visual acuity of 6/12 (right eye) and 6/18 (left eye), with no retinal involvement. His developmental history was notable for delayed milestones, poor academic performance, and social difficulties. He underwent orchidopexy for bilateral cryptorchidism at the age of 15. Following surgery, he had normal testicular development (right: 6 mL, left: 8 mL), Tanner stage III pubic hair, and axillary hair development, but remained short in stature despite otherwise normal puberty. At 16 years of age, he developed patchy hair loss, which was confirmed by biopsy to be cicatricial alopecia. He subsequently underwent fractional CO₂ laser therapy; however, residual scalp involvement persists at his current age. Renal function remained within normal limits until the patient reached 20 years of age, at which time a gradual but continuous decline was documented, requiring sustained nephrology follow-up for monitoring and management. Given the evidence of multi-organ involvement, a comprehensive diagnostic approach was initiated. This included targeted genetic testing alongside a broader range of investigations to better characterize the underlying pathology. On general physical examination, the patient exhibited noticeable dysmorphic features (Fig. 1 ). These included a triangular-shaped face, a high-arched palate, and areas of cicatricial alopecia. Musculoskeletal assessment revealed additional abnormalities such as arachnodactyly, webbed digits, and unusual enlargement of the fingers and toes, with characteristic mallet toe deformities. There were also bilateral inguinal scars, aligning with the patient's documented history of orchidopexy procedures. Systemic examination was unremarkable, with normal findings across the cardiovascular, respiratory, and abdominal systems. Cognitive evaluation indicated mild to moderate intellectual impairment, while neurological assessment revealed no abnormalities. Ophthalmologic evaluation identified refractive errors without evidence of nystagmus or strabismus. Genital examination confirmed prior findings of cryptorchidism, with otherwise normal development of secondary sexual characteristics. Family history revealed a younger brother who died at the age of 10 due to end-stage renal disease (ESRD) of unknown origin, raising concern for a possible inherited disorder affecting kidney function. Laboratory investigations (Table 1 ) demonstrated mild normocytic anemia (Hb: 10.0 g/dL, Hct: 30%) and thrombocytopenia (platelet count: 107 × 10⁹/L), with an elevated erythrocyte sedimentation rate (ESR: 45 mm/hr). Kidney function tests showed mild renal impairment, with a creatinine level of 1.58 mg/dL, urea of 43 mg/dL, and an estimated glomerular filtration rate (eGFR) of approximately 58 mL/min/1.73 m², consistent with stage 2 CKD. Metabolic acidosis was present (pH: 7.30, HCO₃: 21 mEq/L). Electrolyte analysis revealed mild hyponatremia (Na: 132 mEq/L) and borderline hypokalemia (K: 3.78 mEq/L), suggestive of underlying renal tubular dysfunction. Lipid profile indicated hypertriglyceridemia (TG: 236 mg/dL) and low HDL cholesterol (33 mg/dL), consistent with dyslipidemia. Urinalysis revealed mild proteinuria (270–625 mg/day) and polyuria (4 L/day), further supporting impaired tubular function. Endocrine evaluation showed low testosterone levels (66 ng/dL), while cortisol, FSH, LH, and prolactin levels remained within normal limits. Renal imaging demonstrated altered corticomedullary differentiation with increased parenchymal echogenicity, along with the presence of bilateral renal cortical cysts, findings that further corroborate the underlying structural kidney abnormalities (Fig. 2 ). Considering the clinical presentation, laboratory findings, ultrasonographic features suggestive of nephronophthisis, family history of kidney disease, and evidence of multisystem involvement affecting the ocular, renal, endocrine, and skeletal systems, a hereditary disorder was strongly suspected. To confirm the diagnosis and determine the underlying genetic etiology, molecular genetic analysis was performed. Genetic analysis (Table 2 ) identified a homozygous 3′ splice site variant in NPHP4 (c.1764-1G > C), which disrupts the canonical AG acceptor site upstream of exon 15, leading to abnormal splicing. This variant is classified as likely pathogenic and is consistent with known associations of NPHP4 mutations with Nephronophthisis-4 (NPHP4, OMIM #606966) and Senior-Løken Syndrome-4 (SLSN4, OMIM #606996), both of which are characterized by juvenile-onset renal failure and, in the case of SLSN4, early-onset retinal dystrophy. In addition, a homozygous missense variant in RECQL4 (p.Glu1110Lys) was detected and classified as a variant of uncertain significance (VUS). RECQL4 mutations have been linked to Rothmund- Thomson Syndrome type 2 (RTS2, OMIM #268400). Discussion Senior-Løken syndrome (SLSN) is a rare autosomal recessive ciliopathy characterized by a combination of nephronophthisis (NPHP) and retinal dystrophy [ 1 ]. It belongs to the nephronophthisis-related ciliopathies (NPHP-RC), which result from mutations in genes regulating primary cilium function [ 2 , 3 ]. The classical presentation includes progressive renal dysfunction with early-onset polyuria and polydipsia, accompanied by retinal degeneration manifesting as either Leber congenital amaurosis or retinitis pigmentosa [ 4 ]. More than 20 genes have been implicated in SLSN, with NPHP1, NPHP4, IQCB1 (NPHP5), and CEP290 (NPHP6) being the most frequently involved [ 4 ]. However, phenotypic variability is increasingly recognized, especially in patients with mutations affecting multiple ciliopathy-associated genes. The present case involved a patient with non-dialysis-dependent chronic kidney disease (CKD) who was diagnosed with NPHP at 22 years of age, although ocular, tubular, and endocrine manifestations had been present since childhood. Our patient demonstrated the classical features of SLSN-progressive nephronophthisis and tubular dysfunction-along with several deviations suggestive of an expanded ciliopathy spectrum. In addition to an NPHP-related mutation, genetic testing revealed a second mutation in RECQL4, associated with Rothmund- Thomson syndrome (RTS), a rare autosomal recessive disorder. RTS typically presents with dermatological abnormalities, skeletal anomalies, cataracts, and an increased predisposition to malignancies, particularly osteosarcoma. The presence of this second mutation may explain the atypical manifestations observed in our patient. The patient exhibited a typical nephronophthisis phenotype, with early-onset polyuria and polydipsia progressing to CKD. The disease course mirrors existing literature, in which tubular dysfunction precedes glomerular impairment and ultimately leads to end-stage renal disease (ESRD). Our patient had nephrogenic diabetes insipidus since infancy, with proximal tubular acidosis developing at age 16-consistent with reports that nearly all patients with nephronophthisis experience tubular dysfunction between the ages of 10 and 30 years [ 2 , 3 ]. A younger sibling who died of ESRD at the age of 10 further supports an autosomal recessive inheritance pattern, emphasizing the importance of genetic confirmation. Unlike classical SLSN, which is defined by retinal dystrophy, our patient presented with bilateral developmental cataracts and microcornea. Cataracts, although rare in SLSN, are well documented in RTS. RTS is a genodermatosis characterized by early-onset facial poikiloderma, short stature, sparse scalp hair, and reduced eyelashes and eyebrows. Juvenile cataracts are a frequent ocular manifestation, often causing early visual impairment. Skeletal anomalies-including radial ray defects, osteopenia, and increased fracture risk-are also common, reflecting underlying DNA repair defects [ 5 ]. In our patient, optic nerve tortuosity was identified on brain magnetic resonance imaging (MRI). While retinal degeneration remains the hallmark ocular finding in SLSN, some cases with CEP290 mutations have shown optic nerve anomalies and atypical ocular presentations [ 6 ]. Given that RTS is characterized by early- onset cataracts, its co-occurrence in this case suggests that the second mutation may have influenced the ophthalmic phenotype, accounting for the absence of classical retinal dystrophy [ 4 , 6 ]. Follow-up optical coherence tomography (OCT) and electroretinography (ERG) will be valuable in detecting any subtle retinal changes over time. The patient also exhibited bilateral cryptorchidism, short stature, and skeletal abnormalities-features not typical of classical SLSN but described in nephronophthisis-related ciliopathies. However, skeletal anomalies such as arachnodactyly, webbed digits, and disproportionately large fingers and toes are more characteristic of RTS, which is well known for limb abnormalities [ 7 ]. Short stature in this case may be multifactorial. While growth retardation is common in CKD due to chronic metabolic disturbances, RTS is independently associated with growth deficiency due to its effects on DNA repair mechanisms [ 8 ]. Since growth retardation was present before significant renal dysfunction developed, the RTS mutation likely contributed to this phenotype. Cicatricial alopecia, which developed at age 16, is an unusual finding in nephronophthisis-related disorders. While some ciliopathies, such as Joubert syndrome and Bardet-Biedl syndrome, are associated with hair abnormalities, alopecia in NPHP is rare. In contrast, RTS often presents with skin changes including poikiloderma, sparse hair, and skin atrophy [ 9 ]. The presence of cicatricial alopecia in this patient raises the possibility that RECQL4 mutations contributed to this dermatological manifestation. Defective ciliary function may also impair hair follicle regeneration, leading to fibrosis-a hypothesis supported by studies on ciliopathies affecting epidermal differentiation [ 9 ]. Conclusions This case illustrates a rare intersection between Senior-Løken syndrome (SLSN) and Rothmund-Thomson syndrome (RTS), involving coexisting pathogenic variants in the NPHP4 and RECQL4 genes. The patient demonstrated a distinctly atypical phenotype, including nephronophthisis with preserved visual function, developmental cataracts instead of retinal dystrophy, cryptorchidism, skeletal anomalies, and cicatricial alopecia-features that cannot be fully explained by either syndrome in isolation. These findings suggest a blended syndromic expression resulting from concurrent disruption of ciliogenesis and DNA repair pathways. Given the unique multisystem involvement in both this patient and an affected sibling, we propose the recognition of a novel clinical entity, Teelwani syndrome. This report highlights the importance of comprehensive genetic evaluation in patients with syndromic chronic kidney disease. Overlapping genetic disorders-such as ciliopathies and DNA repair syndromes-can substantially alter the clinical phenotype, leading to diagnostic challenges. A better understanding of these complex, multilocus-driven presentations is essential for improving diagnostic precision and for guiding more individualized and targeted therapeutic strategies. Declarations Ethical approval and consent to participate: Written informed consent was obtained from both the patient and the patient's guardian prior to manuscript submission. Specific permission was granted for the use of all clinical data and images related to the patient. All procedures were conducted in accordance with ethical standards, and appropriate consent was secured for publication. Consent for publication: Consent for publicstion has been taken from both the parient and patient’s guardian. Availability of data and material: No datasets were generated or analyzed for this study. Competing interests: The authors declared no conflict of interest. Funding: None. Authors’ Contributions: MT : Conceptualization, Methodology, Software, Validation, Formal Analysis, Data Curation, Writing – Original Draft, Visualization. MMW : Clinical Investigation, Supervision, Data Analysis, Writing – Review and Editing. AF : Methodology, Validation, Supportive Analysis. IAW : Writing – Review and Editing. QN : Writing – Review and Editing. Acknowledgements Thankful To Department Of Endocrinology And Molecular Genetics For Helping Us Out For Management Of Patient. References National Organization for Rare Disorders (NORD). Senior Løken syndrome, 2016. Available: https://rarediseases.org/rare-diseases/senior-loken-syndrome/. Wolf MT, Hildebrandt F. Nephronophthisis. Pediatr Nephrol. 2011 Feb;26(2):181-194. doi:10.1007/s00467-010-1585-z. PMID: 20652329; PMCID: PMC4160028. Tsang SH, Aycinena ARP, Sharma T. Ciliopathy: Senior-Løken Syndrome. Adv Exp Med Biol. 2018;1085:175-178. doi:10.1007/978-3-319-95046-4_34. PMID: 30578507. Ronquillo CC, Bernstein PS, Baehr W. Senior-Løken syndrome: a syndromic form of retinal dystrophy associated with nephronophthisis. Vision Res. 2012 Dec 15;75:88-97. doi:10.1016/j.visres.2012.07.003. PMID: 22819833; PMCID: PMC3504181. Vennos EM, Collins M, James WD. Rothmund-thomson syndrome: Review of the world literature. J Am Acad Dermatol. 1992;27:750–62. doi: 10.1016/0190-9622(92)70249-f. Sahli E, Kiziltunc PB, Idil A. A Report on Children with CEP290 Mutation, Vision Loss, and Developmental Delay. Beyoglu Eye J. 2023 Sep 13;8(3):226-232. doi: 10.14744/bej.2023.37233. PMID: 37766766; PMCID: PMC10521126. Wang LL, Gannavarapu A, Kozinetz CA, Levy ML, Lewis RA, Chintagumpala MM, Ruiz-Maldanado R, Contreras-Ruiz J, Cunniff C, Erickson RP, Lev D, Rogers M, Zackai EH, Plon SE. Association between osteosarcoma and deleterious mutations in the RECQL4 gene in Rothmund-Thomson syndrome. J Natl Cancer Inst. 2003;95:669–74. Mehollin-Ray AR, Kozinetz CA, Schlesinger AE, Guillerman RP, Wang LL. Radiographic abnormalities in Rothmund-Thomson syndrome and genotype-phenotype correlation with RECQL4 mutation status. AJR Am J Roentgenol. 2008;191:W62-6. Zhang Y, Qin W, Wang H, Lin Z, Tang Z, Xu Z. Novel pathogenic variants in the RECQL4 gene causing Rothmund-Thomson syndrome in three Chinese patients. J Dermatol. 2021 Oct;48(10):1511-1517. doi: 10.1111/1346-8138.16015. Epub 2021 Jun 22. PMID: 34155702. Tables Tables 1 and 2 are available in the Supplementary Files section. Additional Declarations The authors declare no competing interests. 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(b) triangular facies with dental abnormalities; (c) high-arched palate; (d) mallet toe deformities with flexion at the distal interphalangeal joints; and (e) arachnodactyly, 3rd/4th digit syndactyly, and enlarged fingers and toes.\u003c/strong\u003e\u003c/p\u003e","description":"","filename":"image1.jpeg","url":"https://assets-eu.researchsquare.com/files/rs-7432684/v1/b05210786b8a903c3cdd25fb.jpeg"},{"id":89990225,"identity":"8eb2e91e-dc22-49c5-b248-18aafd1388be","added_by":"auto","created_at":"2025-08-27 07:10:14","extension":"jpeg","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":56159,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eUltrasound image showing a) left kidney shows multiple cortical cysts largest measuring 10mm consistent with nephronophthisis, accompanied by lost corticomedullary differentiation (CMD) b) right kidney showing multiple cortical cysts and loss of renal echopattern as compared to liver.\u003c/strong\u003e\u003c/p\u003e","description":"","filename":"image2.jpeg","url":"https://assets-eu.researchsquare.com/files/rs-7432684/v1/5626895428589eb8a34013c3.jpeg"},{"id":89990293,"identity":"d280a829-519b-4358-969a-57603ba0ab0f","added_by":"auto","created_at":"2025-08-27 07:10:28","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":834681,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-7432684/v1/31eb00a0-00bf-4236-b843-fb20c0cb16de.pdf"},{"id":89990232,"identity":"e2e65587-c86a-46b8-905f-46f4a72f3b6a","added_by":"auto","created_at":"2025-08-27 07:10:15","extension":"docx","order_by":1,"title":"","display":"","copyAsset":false,"role":"supplement","size":38741,"visible":true,"origin":"","legend":"","description":"","filename":"teelwanigeneticstables.docx","url":"https://assets-eu.researchsquare.com/files/rs-7432684/v1/49102de447e74bc9cf64961a.docx"}],"financialInterests":"The authors declare no competing interests.","formattedTitle":"\u003cp\u003e\u003cstrong\u003eExpanding the Senior-Løken syndrome spectrum: Combined Rothmund-Thomson features unveil the distinct Teelwani Syndrome phenotype\u003c/strong\u003e\u003c/p\u003e","fulltext":[{"header":"Introduction","content":"\u003cp\u003eSenior-L\u0026oslash;ken syndrome (SLS) is a rare autosomal recessive disorder characterized by the coexistence of nephronophthisis (NPH) and retinal dystrophy, both resulting from defects in primary cilia function [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e]. 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 presents as either Leber congenital amaurosis or late-onset pigmentary retinopathy, causing progressive visual impairment. The estimated prevalence of SLS is approximately 1 in 50,000 live births, accounting for 10\u0026ndash;15% of NPH cases [\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e].\u003c/p\u003e\u003cp\u003eWhile the renal-retinal phenotype is well established, reports of additional systemic involvement - including skeletal abnormalities, endocrine dysfunction, and neurological deficits - suggest a broader ciliopathy spectrum [\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e]. We report a genetically confirmed case of SLS with several uncommon features, including proximal renal tubular acidosis (RTA), cryptorchidism, empty sella syndrome, intellectual disability, and skeletal anomalies such as webbed toes and mallet toes. These findings expand the phenotypic spectrum of SLS and underscore the need for comprehensive evaluation in patients with suspected ciliopathies. This case highlights the importance of recognizing atypical manifestations, which may have implications for early diagnosis, genetic counseling, and long-term management.\u003c/p\u003e"},{"header":"Case Presentation","content":"\u003cp\u003eWe report the case of a 22-year-old male, born of a consanguineous marriage, who had progressive polyuria and polydipsia since infancy, leading to a diagnosis of nephrogenic diabetes insipidus (NDI) at the age of 16. His symptoms were first noticed in infancy, with excessive diaper wetting, persistent bedwetting, and an unusually high fluid intake, which continued into adolescence. A water deprivation test confirmed NDI, and a pituitary MRI revealed an absent posterior pituitary bright spot with optic nerve tortuosity. He was initially started on desmopressin and later switched to thiazide diuretics for better symptom control.\u003c/p\u003e\n\u003cp\u003eIn addition to NDI, he had a history of bilateral developmental cataracts identified at the age of nine due to poor vision and whitish pupillary reflexes. He underwent bilateral cataract extraction with posterior chamber intraocular lens placement and now has corrected visual acuity of 6/12 (right eye) and 6/18 (left eye), with no retinal involvement. His developmental history was notable for delayed milestones, poor academic performance, and social difficulties.\u003c/p\u003e\n\u003cp\u003eHe underwent orchidopexy for bilateral cryptorchidism at the age of 15. Following surgery, he had normal testicular development (right: 6 mL, left: 8 mL), Tanner stage III pubic hair, and axillary hair development, but remained short in stature despite otherwise normal puberty.\u003c/p\u003e\n\u003cp\u003eAt 16 years of age, he developed patchy hair loss, which was confirmed by biopsy to be cicatricial alopecia. He subsequently underwent fractional CO₂ laser therapy; however, residual scalp involvement persists at his current age.\u003c/p\u003e\n\u003cp\u003eRenal function remained within normal limits until the patient reached 20 years of age, at which time a gradual but continuous decline was documented, requiring sustained nephrology follow-up for monitoring and management. Given the evidence of multi-organ involvement, a comprehensive diagnostic approach was initiated. This included targeted genetic testing alongside a broader range of investigations to better characterize the underlying pathology.\u003c/p\u003e\n\u003cp\u003eOn general physical examination, the patient exhibited noticeable dysmorphic features (Fig. \u003cspan class=\"InternalRef\"\u003e1\u003c/span\u003e). These included a triangular-shaped face, a high-arched palate, and areas of cicatricial alopecia. Musculoskeletal assessment revealed additional abnormalities such as arachnodactyly, webbed digits, and unusual enlargement of the fingers and toes, with characteristic mallet toe deformities. There were also bilateral inguinal scars, aligning with the patient\u0026apos;s documented history of orchidopexy procedures.\u003c/p\u003e\n\u003cp\u003eSystemic examination was unremarkable, with normal findings across the cardiovascular, respiratory, and abdominal systems. Cognitive evaluation indicated mild to moderate intellectual impairment, while neurological assessment revealed no abnormalities. Ophthalmologic evaluation identified refractive errors without evidence of nystagmus or strabismus. Genital examination confirmed prior findings of cryptorchidism, with otherwise normal development of secondary sexual characteristics.\u003c/p\u003e\n\u003cp\u003eFamily history revealed a younger brother who died at the age of 10 due to end-stage renal disease (ESRD) of unknown origin, raising concern for a possible inherited disorder affecting kidney function.\u003c/p\u003e\n\u003cp\u003eLaboratory investigations (Table \u003cspan class=\"InternalRef\"\u003e1\u003c/span\u003e) demonstrated mild normocytic anemia (Hb: 10.0 g/dL, Hct: 30%) and thrombocytopenia (platelet count: 107 \u0026times; 10⁹/L), with an elevated erythrocyte sedimentation rate (ESR: 45 mm/hr). Kidney function tests showed mild renal impairment, with a creatinine level of 1.58 mg/dL, urea of 43 mg/dL, and an estimated glomerular filtration rate (eGFR) of approximately 58 mL/min/1.73 m\u0026sup2;, consistent with stage 2 CKD. Metabolic acidosis was present (pH: 7.30, HCO₃: 21 mEq/L). Electrolyte analysis revealed mild hyponatremia (Na: 132 mEq/L) and borderline hypokalemia (K: 3.78 mEq/L), suggestive of underlying renal tubular dysfunction. Lipid profile indicated hypertriglyceridemia (TG: 236 mg/dL) and low HDL cholesterol (33 mg/dL), consistent with dyslipidemia. Urinalysis revealed mild proteinuria (270\u0026ndash;625 mg/day) and polyuria (4 L/day), further supporting impaired tubular function. Endocrine evaluation showed low testosterone levels (66 ng/dL), while cortisol, FSH, LH, and prolactin levels remained within normal limits.\u003c/p\u003e\n\u003cp\u003eRenal imaging demonstrated altered corticomedullary differentiation with increased parenchymal echogenicity, along with the presence of bilateral renal cortical cysts, findings that further corroborate the underlying structural kidney abnormalities (Fig. \u003cspan class=\"InternalRef\"\u003e2\u003c/span\u003e).\u003c/p\u003e\n\u003cp\u003eConsidering the clinical presentation, laboratory findings, ultrasonographic features suggestive of nephronophthisis, family history of kidney disease, and evidence of multisystem involvement affecting the ocular, renal, endocrine, and skeletal systems, a hereditary disorder was strongly suspected. To confirm the diagnosis and determine the underlying genetic etiology, molecular genetic analysis was performed.\u003c/p\u003e\n\u003cp\u003eGenetic analysis (Table \u003cspan class=\"InternalRef\"\u003e2\u003c/span\u003e) identified a homozygous 3\u0026prime; splice site variant in NPHP4 (c.1764-1G\u0026thinsp;\u0026gt;\u0026thinsp;C), which disrupts the canonical AG acceptor site upstream of exon 15, leading to abnormal splicing. This variant is classified as likely pathogenic and is consistent with known associations of NPHP4 mutations with Nephronophthisis-4 (NPHP4, OMIM #606966) and Senior-L\u0026oslash;ken Syndrome-4 (SLSN4, OMIM #606996), both of which are characterized by juvenile-onset renal failure and, in the case of SLSN4, early-onset retinal dystrophy. In addition, a homozygous missense variant in RECQL4 (p.Glu1110Lys) was detected and classified as a variant of uncertain significance (VUS). RECQL4 mutations have been linked to Rothmund- Thomson Syndrome type 2 (RTS2, OMIM #268400).\u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eSenior-L\u0026oslash;ken syndrome (SLSN) is a rare autosomal recessive ciliopathy characterized by a combination of nephronophthisis (NPHP) and retinal dystrophy [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e]. It belongs to the nephronophthisis-related ciliopathies (NPHP-RC), which result from mutations in genes regulating primary cilium function [\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e, \u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e]. The classical presentation includes progressive renal dysfunction with early-onset polyuria and polydipsia, accompanied by retinal degeneration manifesting as either Leber congenital amaurosis or retinitis pigmentosa [\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e]. More than 20 genes have been implicated in SLSN, with NPHP1, NPHP4, IQCB1 (NPHP5), and CEP290 (NPHP6) being the most frequently involved [\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e]. However, phenotypic variability is increasingly recognized, especially in patients with mutations affecting multiple ciliopathy-associated genes.\u003c/p\u003e\u003cp\u003eThe present case involved a patient with non-dialysis-dependent chronic kidney disease (CKD) who was diagnosed with NPHP at 22 years of age, although ocular, tubular, and endocrine manifestations had been present since childhood.\u003c/p\u003e\u003cp\u003eOur patient demonstrated the classical features of SLSN-progressive nephronophthisis and tubular dysfunction-along with several deviations suggestive of an expanded ciliopathy spectrum. In addition to an NPHP-related mutation, genetic testing revealed a second mutation in RECQL4, associated with Rothmund- Thomson syndrome (RTS), a rare autosomal recessive disorder. RTS typically presents with dermatological abnormalities, skeletal anomalies, cataracts, and an increased predisposition to malignancies, particularly osteosarcoma. The presence of this second mutation may explain the atypical manifestations observed in our patient.\u003c/p\u003e\u003cp\u003eThe patient exhibited a typical nephronophthisis phenotype, with early-onset polyuria and polydipsia progressing to CKD. The disease course mirrors existing literature, in which tubular dysfunction precedes glomerular impairment and ultimately leads to end-stage renal disease (ESRD). Our patient had\u003c/p\u003e\u003cp\u003enephrogenic diabetes insipidus since infancy, with proximal tubular acidosis developing at age 16-consistent with reports that nearly all patients with nephronophthisis experience tubular dysfunction between the ages of 10 and 30 years [\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e, \u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e]. A younger sibling who died of ESRD at the age of 10 further supports an autosomal recessive inheritance pattern, emphasizing the importance of genetic confirmation. Unlike classical SLSN, which is defined by retinal dystrophy, our patient presented with bilateral developmental cataracts and microcornea. Cataracts, although rare in SLSN, are well documented in RTS. RTS is a genodermatosis characterized by early-onset facial poikiloderma, short stature, sparse scalp hair, and reduced eyelashes and eyebrows. Juvenile cataracts are a\u003c/p\u003e\u003cp\u003efrequent ocular manifestation, often causing early visual impairment.\u003c/p\u003e\u003cp\u003eSkeletal anomalies-including radial ray defects, osteopenia, and increased fracture risk-are also common, reflecting underlying DNA repair defects [\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e].\u003c/p\u003e\u003cp\u003eIn our patient, optic nerve tortuosity was identified on brain magnetic resonance imaging (MRI). While retinal degeneration remains the hallmark ocular finding in SLSN, some cases with CEP290 mutations have shown optic nerve anomalies and atypical ocular presentations [\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e]. Given that RTS is characterized by early- onset cataracts, its co-occurrence in this case suggests that the second mutation may have influenced the ophthalmic phenotype, accounting for the absence of classical retinal dystrophy [\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e, \u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e]. Follow-up optical coherence tomography (OCT) and electroretinography (ERG) will be valuable in detecting any subtle retinal changes over time.\u003c/p\u003e\u003cp\u003eThe patient also exhibited bilateral cryptorchidism, short stature, and skeletal abnormalities-features not typical of classical SLSN but described in nephronophthisis-related ciliopathies. However, skeletal anomalies such as arachnodactyly, webbed digits, and disproportionately large fingers and toes are more characteristic of RTS, which is well known for limb abnormalities [\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e]. Short stature in this case may be multifactorial. While growth retardation is common in CKD due to chronic metabolic disturbances, RTS is independently associated with growth deficiency due to its effects on DNA repair mechanisms [\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e]. Since growth retardation was present before significant renal dysfunction developed, the RTS mutation likely contributed to this phenotype.\u003c/p\u003e\u003cp\u003eCicatricial alopecia, which developed at age 16, is an unusual finding in nephronophthisis-related disorders. While some ciliopathies, such as Joubert syndrome and Bardet-Biedl syndrome, are associated with hair abnormalities, alopecia in NPHP is rare. In contrast, RTS often presents with skin changes including poikiloderma, sparse hair, and skin atrophy [\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e]. The presence of cicatricial alopecia in this patient raises the possibility that RECQL4 mutations contributed to this dermatological manifestation. Defective ciliary function may also impair hair follicle regeneration, leading to fibrosis-a hypothesis supported by studies on ciliopathies affecting epidermal differentiation [\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e].\u003c/p\u003e"},{"header":"Conclusions","content":"\u003cp\u003eThis case illustrates a rare intersection between Senior-L\u0026oslash;ken syndrome (SLSN) and Rothmund-Thomson syndrome (RTS), involving coexisting pathogenic variants in the NPHP4 and RECQL4 genes. The patient demonstrated a distinctly atypical phenotype, including nephronophthisis with preserved visual function, developmental cataracts instead of retinal dystrophy, cryptorchidism, skeletal anomalies, and cicatricial alopecia-features that cannot be fully explained by either syndrome in isolation. These findings suggest a blended syndromic expression resulting from concurrent disruption of ciliogenesis and DNA repair pathways. Given the unique multisystem involvement in both this patient and an affected sibling, we propose the recognition of a novel clinical entity, Teelwani syndrome.\u003c/p\u003e\u003cp\u003eThis report highlights the importance of comprehensive genetic evaluation in patients with syndromic chronic kidney disease. Overlapping genetic disorders-such as ciliopathies and DNA repair syndromes-can substantially alter the clinical phenotype, leading to diagnostic challenges. A better understanding of these complex, multilocus-driven presentations is essential for improving diagnostic precision and for guiding more individualized and targeted therapeutic strategies.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eEthical approval and consent to participate:\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eWritten informed consent was obtained from both the patient and the patient\u0026apos;s guardian prior to manuscript submission. Specific permission was granted for the use of all clinical data and images related to the patient. All procedures were conducted in accordance with ethical standards, and appropriate consent was secured for publication.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConsent for publication:\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eConsent for publicstion has been taken from both the parient and patient\u0026rsquo;s guardian.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAvailability of data and material:\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNo datasets were generated or analyzed for this study.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCompeting interests:\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors declared no conflict of interest.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding:\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNone.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthors\u0026rsquo; Contributions:\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eMT\u003c/strong\u003e: Conceptualization, Methodology, Software, Validation, Formal Analysis, Data Curation, Writing \u0026ndash; Original Draft, Visualization.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eMMW\u003c/strong\u003e: Clinical Investigation, Supervision, Data Analysis, Writing \u0026ndash; Review and Editing.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAF\u003c/strong\u003e: Methodology, Validation, Supportive Analysis.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eIAW\u003c/strong\u003e: Writing \u0026ndash; Review and Editing.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eQN\u003c/strong\u003e : Writing \u0026ndash; Review and Editing.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAcknowledgements\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThankful To Department Of Endocrinology And Molecular Genetics For Helping Us Out For Management Of Patient.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n \u003cli\u003eNational Organization for Rare Disorders (NORD). Senior L\u0026oslash;ken syndrome, 2016. Available: https://rarediseases.org/rare-diseases/senior-loken-syndrome/.\u003c/li\u003e\n \u003cli\u003eWolf MT, Hildebrandt F. Nephronophthisis. Pediatr Nephrol. 2011 Feb;26(2):181-194. doi:10.1007/s00467-010-1585-z. PMID: 20652329; PMCID: PMC4160028.\u003c/li\u003e\n \u003cli\u003eTsang SH, Aycinena ARP, Sharma T. Ciliopathy: Senior-L\u0026oslash;ken Syndrome. Adv Exp Med Biol. 2018;1085:175-178. doi:10.1007/978-3-319-95046-4_34. PMID: 30578507.\u003c/li\u003e\n \u003cli\u003eRonquillo CC, Bernstein PS, Baehr W. Senior-L\u0026oslash;ken syndrome: a syndromic form of retinal dystrophy associated with nephronophthisis. Vision Res. 2012 Dec 15;75:88-97. doi:10.1016/j.visres.2012.07.003. PMID: 22819833; PMCID: PMC3504181.\u003c/li\u003e\n \u003cli\u003eVennos EM, Collins M, James WD. Rothmund-thomson syndrome: Review of the world literature. J Am Acad Dermatol. 1992;27:750\u0026ndash;62. doi: 10.1016/0190-9622(92)70249-f.\u003c/li\u003e\n \u003cli\u003eSahli E, Kiziltunc PB, Idil A. A Report on Children with CEP290 Mutation, Vision Loss, and Developmental Delay. Beyoglu Eye J. 2023 Sep 13;8(3):226-232. doi: 10.14744/bej.2023.37233. PMID: 37766766; PMCID: PMC10521126.\u003c/li\u003e\n \u003cli\u003eWang LL, Gannavarapu A, Kozinetz CA, Levy ML, Lewis RA, Chintagumpala MM, Ruiz-Maldanado R, Contreras-Ruiz J, Cunniff C, Erickson RP, Lev D, Rogers M, Zackai EH, Plon SE. Association between osteosarcoma and deleterious mutations in the RECQL4 gene in Rothmund-Thomson syndrome. J Natl Cancer Inst. 2003;95:669\u0026ndash;74.\u003c/li\u003e\n \u003cli\u003eMehollin-Ray AR, Kozinetz CA, Schlesinger AE, Guillerman RP, Wang LL. Radiographic abnormalities in Rothmund-Thomson syndrome and genotype-phenotype correlation with RECQL4 mutation status. AJR Am J Roentgenol. 2008;191:W62-6.\u003c/li\u003e\n \u003cli\u003eZhang Y, Qin W, Wang H, Lin Z, Tang Z, Xu Z. Novel pathogenic variants in the RECQL4 gene causing Rothmund-Thomson syndrome in three Chinese patients. J Dermatol. 2021 Oct;48(10):1511-1517. doi: 10.1111/1346-8138.16015. Epub 2021 Jun 22. PMID: 34155702.\u003c/li\u003e\n\u003c/ol\u003e"},{"header":"Tables","content":"\u003cp\u003eTables 1 and 2 are available in the Supplementary Files section.\u003c/p\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":true,"hideJournal":true,"highlight":"","institution":"Sher-i-Kashmir Institute of Medical Sciences","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"Senior-Løken syndrome, Nephronophthisis, Ciliopathy, Nephrogenic diabetes insipidus, Teelwani Syndrome","lastPublishedDoi":"10.21203/rs.3.rs-7432684/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-7432684/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e\u003cstrong\u003eBackground :\u003c/strong\u003e\u0026nbsp;Senior-Løken Syndrome (SLSN) is a rare autosomal recessive typically \u0026nbsp;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\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCase Summary : \u003c/strong\u003eThis 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 \u0026nbsp;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.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConclusion :\u003c/strong\u003e\u0026nbsp;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.\u003c/p\u003e","manuscriptTitle":"Expanding the Senior-Løken syndrome spectrum: Combined Rothmund-Thomson features unveil the distinct Teelwani Syndrome phenotype","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-08-27 07:09:26","doi":"10.21203/rs.3.rs-7432684/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"f6fa364f-fb76-478f-a73d-7d140d62f150","owner":[],"postedDate":"August 27th, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[{"id":53560614,"name":"Urology \u0026 Nephrology"},{"id":53560615,"name":"Molecular Genetics"}],"tags":[],"updatedAt":"2025-08-27T07:09:26+00:00","versionOfRecord":[],"versionCreatedAt":"2025-08-27 07:09:26","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-7432684","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-7432684","identity":"rs-7432684","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}