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Senior-Loken syndrome 4(SLSN4)

MedGen UID:
337697
Concept ID:
C1846979
Disease or Syndrome
Synonym: SLSN4
 
Gene (location): NPHP4 (1p36.31)
 
Monarch Initiative: MONDO:0011756
OMIM®: 606996

Definition

Senior-Loken syndrome-4 (SLSN4) is an autosomal recessive disorder characterized by the association of the cystic renal disorder nephronophthisis with late-onset retinitis pigmentosa (Schuermann et al., 2002). For a general phenotypic description and a discussion of genetic heterogeneity of Senior-Loken syndrome, see 266900. [from OMIM]

Additional description

From MedlinePlus Genetics
Leber congenital amaurosis primarily affects the retina, which is the specialized tissue at the back of the eye that detects light and color. This condition causes vision problems, including an increased sensitivity to light (photophobia), involuntary movements of the eyes (nystagmus), and extreme farsightedness (hyperopia). Some people with Senior-Løken syndrome develop the signs of Leber congenital amaurosis within the first few years of life, while others do not develop vision problems until later in childhood.

Nephronophthisis causes fluid-filled cysts to develop in the kidneys beginning in childhood. These cysts impair kidney function, initially causing increased urine production (polyuria), excessive thirst (polydipsia), general weakness, and extreme tiredness (fatigue). Nephronophthisis leads to end-stage renal disease (ESRD) later in childhood or in adolescence. ESRD is a life-threatening failure of kidney function that occurs when the kidneys are no longer able to filter fluids and waste products from the body effectively.

Senior-Løken syndrome is a rare disorder characterized by the combination of two specific features: a kidney condition called nephronophthisis and an eye condition known as Leber congenital amaurosis.  https://medlineplus.gov/genetics/condition/senior-loken-syndrome

Clinical features

From HPO
Polyuria
MedGen UID:
19404
Concept ID:
C0032617
Sign or Symptom
An increased rate of urine production.
Nephronophthisis
MedGen UID:
146912
Concept ID:
C0687120
Disease or Syndrome
The nephronophthisis (NPH) phenotype is characterized by reduced renal concentrating ability, chronic tubulointerstitial nephritis, cystic renal disease, and progression to end-stage renal disease (ESRD) before age 30 years. Three age-based clinical subtypes are recognized: infantile, juvenile, and adolescent/adult. Infantile NPH can present in utero with oligohydramnios sequence (limb contractures, pulmonary hypoplasia, and facial dysmorphisms) or postnatally with renal manifestations that progress to ESRD before age 3 years. Juvenile NPH, the most prevalent subtype, typically presents with polydipsia and polyuria, growth retardation, chronic iron-resistant anemia, or other findings related to chronic kidney disease (CKD). Hypertension is typically absent due to salt wasting. ESRD develops at a median age of 13 years. Ultrasound findings are increased echogenicity, reduced corticomedullary differentiation, and renal cysts (in 50% of affected individuals). Histologic findings include tubulointerstitial fibrosis, thickened and disrupted tubular basement membrane, sporadic corticomedullary cysts, and normal or reduced kidney size. Adolescent/adult NPH is clinically similar to juvenile NPH, but ESRD develops at a median age of 19 years. Within a subtype, inter- and intrafamilial variability in rate of progression to ESRD is considerable. Approximately 80%-90% of individuals with the NPH phenotype have no extrarenal features (i.e., they have isolated NPH); ~10%-20% have extrarenal manifestations that constitute a recognizable syndrome (e.g., Joubert syndrome, Bardet-Biedl syndrome, Jeune syndrome and related skeletal disorders, Meckel-Gruber syndrome, Senior-Løken syndrome, Leber congenital amaurosis, COACH syndrome, and oculomotor apraxia, Cogan type).
Stage 5 chronic kidney disease
MedGen UID:
384526
Concept ID:
C2316810
Disease or Syndrome
A degree of kidney failure severe enough to require dialysis or kidney transplantation for survival characterized by a severe reduction in glomerular filtration rate (less than 15 ml/min/1.73 m2) and other manifestations including increased serum creatinine.
Polydipsia
MedGen UID:
43214
Concept ID:
C0085602
Sign or Symptom
Excessive thirst manifested by excessive fluid intake.
Anemia
MedGen UID:
1526
Concept ID:
C0002871
Disease or Syndrome
A reduction in erythrocytes volume or hemoglobin concentration.
Amblyopia
MedGen UID:
8009
Concept ID:
C0002418
Disease or Syndrome
Reduced visual acuity that is uncorrectable by lenses in the absence of detectable anatomic defects in the eye or visual pathways.
Rotary nystagmus
MedGen UID:
116106
Concept ID:
C0240595
Disease or Syndrome
A form of nystagmus in which the eyeball makes rotary motions around the axis.
Severely reduced visual acuity
MedGen UID:
226987
Concept ID:
C1301509
Disease or Syndrome
Severe reduction of the ability to see defined as visual acuity less than 6/60 (20/200 in US notation; 0.1 in decimal notation) but at least 3/60 (20/400 in US notation; 0.05 in decimal notation).
Rod-cone dystrophy
MedGen UID:
1632921
Concept ID:
C4551714
Disease or Syndrome
An inherited retinal disease subtype in which the rod photoreceptors appear to be more severely affected than the cone photoreceptors. Typical presentation is with nyctalopia (due to rod dysfunction) followed by loss of mid-peripheral field of vision, which gradually extends and leaves many patients with a small central island of vision due to the preservation of macular cones.

Professional guidelines

PubMed

Casteels I, Spileers W, Demaerel P, Casaer P, De Cock P, Dralands L, Missotten L
Neuropediatrics 1996 Aug;27(4):189-93. doi: 10.1055/s-2007-973785. PMID: 8892367

Recent clinical studies

Etiology

Wang J, Li S, Jiang Y, Wang Y, Ouyang J, Yi Z, Sun W, Jia X, Xiao X, Wang P, Zhang Q
Am J Ophthalmol 2023 Aug;252:188-204. Epub 2023 Mar 27 doi: 10.1016/j.ajo.2023.03.025. PMID: 36990420
Tay SA, Vincent AL
Ophthalmic Genet 2020 Aug;41(4):354-357. Epub 2020 May 20 doi: 10.1080/13816810.2020.1766086. PMID: 32432520
Surl D, Shin S, Lee ST, Choi JR, Lee J, Byeon SH, Han SH, Lim HT, Han J
Mol Vis 2020;26:26-35. Epub 2020 Feb 24 PMID: 32165824Free PMC Article
König J, Kranz B, König S, Schlingmann KP, Titieni A, Tönshoff B, Habbig S, Pape L, Häffner K, Hansen M, Büscher A, Bald M, Billing H, Schild R, Walden U, Hampel T, Staude H, Riedl M, Gretz N, Lablans M, Bergmann C, Hildebrandt F, Omran H, Konrad M; Gesellschaft für Pädiatrische Nephrologie (GPN)
Clin J Am Soc Nephrol 2017 Dec 7;12(12):1974-1983. Epub 2017 Nov 16 doi: 10.2215/CJN.01280217. PMID: 29146700Free PMC Article
Casteels I, Spileers W, Demaerel P, Casaer P, De Cock P, Dralands L, Missotten L
Neuropediatrics 1996 Aug;27(4):189-93. doi: 10.1055/s-2007-973785. PMID: 8892367

Diagnosis

Wang J, Li S, Jiang Y, Wang Y, Ouyang J, Yi Z, Sun W, Jia X, Xiao X, Wang P, Zhang Q
Am J Ophthalmol 2023 Aug;252:188-204. Epub 2023 Mar 27 doi: 10.1016/j.ajo.2023.03.025. PMID: 36990420
Tay SA, Vincent AL
Ophthalmic Genet 2020 Aug;41(4):354-357. Epub 2020 May 20 doi: 10.1080/13816810.2020.1766086. PMID: 32432520
Surl D, Shin S, Lee ST, Choi JR, Lee J, Byeon SH, Han SH, Lim HT, Han J
Mol Vis 2020;26:26-35. Epub 2020 Feb 24 PMID: 32165824Free PMC Article
Roozbeh J, Sharifian M, Hosseini H, Sagheb MM, Behzadi S, Raeisjalali GA, Iraniparast A, Afshariani R, Tohidi M, Sharifian M
Saudi J Kidney Dis Transpl 2010 Jul;21(4):735-7. PMID: 20587883
Simms RJ, Eley L, Sayer JA
Eur J Hum Genet 2009 Apr;17(4):406-16. Epub 2008 Dec 10 doi: 10.1038/ejhg.2008.238. PMID: 19066617Free PMC Article

Therapy

Bartiromo M, Borchi B, Botta A, Bagalà A, Lugli G, Tilli M, Cavallo A, Xhaferi B, Cutruzzulà R, Vaglio A, Bresci S, Larti A, Bartoloni A, Cirami C
Transpl Infect Dis 2020 Aug;22(4):e13286. Epub 2020 Jul 14 doi: 10.1111/tid.13286. PMID: 32279418Free PMC Article

Prognosis

Tay SA, Vincent AL
Ophthalmic Genet 2020 Aug;41(4):354-357. Epub 2020 May 20 doi: 10.1080/13816810.2020.1766086. PMID: 32432520
König J, Kranz B, König S, Schlingmann KP, Titieni A, Tönshoff B, Habbig S, Pape L, Häffner K, Hansen M, Büscher A, Bald M, Billing H, Schild R, Walden U, Hampel T, Staude H, Riedl M, Gretz N, Lablans M, Bergmann C, Hildebrandt F, Omran H, Konrad M; Gesellschaft für Pädiatrische Nephrologie (GPN)
Clin J Am Soc Nephrol 2017 Dec 7;12(12):1974-1983. Epub 2017 Nov 16 doi: 10.2215/CJN.01280217. PMID: 29146700Free PMC Article
Tong H, Yue Z, Sun L, Chen H, Wang W, Wang H
Nephrology (Carlton) 2013 Dec;18(12):838-42. doi: 10.1111/nep.12156. PMID: 24674142
Roepman R, Letteboer SJ, Arts HH, van Beersum SE, Lu X, Krieger E, Ferreira PA, Cremers FP
Proc Natl Acad Sci U S A 2005 Dec 20;102(51):18520-5. Epub 2005 Dec 9 doi: 10.1073/pnas.0505774102. PMID: 16339905Free PMC Article
Casteels I, Spileers W, Demaerel P, Casaer P, De Cock P, Dralands L, Missotten L
Neuropediatrics 1996 Aug;27(4):189-93. doi: 10.1055/s-2007-973785. PMID: 8892367

Clinical prediction guides

Wang J, Li S, Jiang Y, Wang Y, Ouyang J, Yi Z, Sun W, Jia X, Xiao X, Wang P, Zhang Q
Am J Ophthalmol 2023 Aug;252:188-204. Epub 2023 Mar 27 doi: 10.1016/j.ajo.2023.03.025. PMID: 36990420
König J, Kranz B, König S, Schlingmann KP, Titieni A, Tönshoff B, Habbig S, Pape L, Häffner K, Hansen M, Büscher A, Bald M, Billing H, Schild R, Walden U, Hampel T, Staude H, Riedl M, Gretz N, Lablans M, Bergmann C, Hildebrandt F, Omran H, Konrad M; Gesellschaft für Pädiatrische Nephrologie (GPN)
Clin J Am Soc Nephrol 2017 Dec 7;12(12):1974-1983. Epub 2017 Nov 16 doi: 10.2215/CJN.01280217. PMID: 29146700Free PMC Article
Tong H, Yue Z, Sun L, Chen H, Wang W, Wang H
Nephrology (Carlton) 2013 Dec;18(12):838-42. doi: 10.1111/nep.12156. PMID: 24674142
Salomon R, Saunier S, Niaudet P
Pediatr Nephrol 2009 Dec;24(12):2333-44. Epub 2008 Jul 8 doi: 10.1007/s00467-008-0840-z. PMID: 18607645Free PMC Article
Chance PF, Cavalier L, Satran D, Pellegrino JE, Koenig M, Dobyns WB
J Child Neurol 1999 Oct;14(10):660-6; discussion 669-72. doi: 10.1177/088307389901401007. PMID: 10511339

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