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Senior-Loken syndrome 6(SLSN6)

MedGen UID:
387907
Concept ID:
C1857779
Disease or Syndrome
Synonym: SLSN6
 
Gene (location): CEP290 (12q21.32)
 
Monarch Initiative: MONDO:0012433
OMIM®: 610189

Definition

Senior-Loken syndrome-6 (SLSN6) is an autosomal recessive disorder characterized by the association of nephronophthisis resulting in end-stage renal disease in the second decade of life with retinal degeneration (Sayer et al., 2006). For a 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
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.
Aplasia/Hypoplasia of the cerebellar vermis
MedGen UID:
340931
Concept ID:
C1855676
Congenital Abnormality
Absence or underdevelopment of the vermis of cerebellum.
Reduced visual acuity
MedGen UID:
65889
Concept ID:
C0234632
Finding
Diminished clarity of vision.
Visual impairment
MedGen UID:
777085
Concept ID:
C3665347
Finding
Visual impairment (or vision impairment) is vision loss (of a person) to such a degree as to qualify as an additional support need through a significant limitation of visual capability resulting from either disease, trauma, or congenital or degenerative conditions that cannot be corrected by conventional means, such as refractive correction, medication, or surgery.
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

Coppieters F, Casteels I, Meire F, De Jaegere S, Hooghe S, van Regemorter N, Van Esch H, Matuleviciene A, Nunes L, Meersschaut V, Walraedt S, Standaert L, Coucke P, Hoeben H, Kroes HY, Vande Walle J, de Ravel T, Leroy BP, De Baere E
Hum Mutat 2010 Oct;31(10):E1709-66. doi: 10.1002/humu.21336. PMID: 20683928Free PMC Article

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
Yahalom C, Volovelsky O, Macarov M, Altalbishi A, Alsweiti Y, Schneider N, Hanany M, Khan MI, Cremers FPM, Anteby I, Banin E, Sharon D, Khateb S
Retina 2021 Oct 1;41(10):2179-2187. doi: 10.1097/IAE.0000000000003138. PMID: 33512896
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
Otto EA, Tory K, Attanasio M, Zhou W, Chaki M, Paruchuri Y, Wise EL, Wolf MT, Utsch B, Becker C, Nürnberg G, Nürnberg P, Nayir A, Saunier S, Antignac C, Hildebrandt F
J Med Genet 2009 Oct;46(10):663-70. Epub 2009 Jun 8 doi: 10.1136/jmg.2009.066613. PMID: 19508969
Hildebrandt F, Singh-Sawhney I, Schnieders B, Centofante L, Omran H, Pohlmann A, Schmaltz C, Wedekind H, Schubotz C, Antignac C
Am J Hum Genet 1993 Dec;53(6):1256-61. PMID: 8250041Free PMC Article

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
Yahalom C, Volovelsky O, Macarov M, Altalbishi A, Alsweiti Y, Schneider N, Hanany M, Khan MI, Cremers FPM, Anteby I, Banin E, Sharon D, Khateb S
Retina 2021 Oct 1;41(10):2179-2187. doi: 10.1097/IAE.0000000000003138. PMID: 33512896
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
Sekiya K, Nakazawa M, Tanaka H
Jpn J Ophthalmol 2001 Nov-Dec;45(6):636-9. doi: 10.1016/s0021-5155(01)00424-5. PMID: 11754908
De Laey JJ
Bull Soc Belge Ophtalmol 1991;241:41-50. PMID: 1840995

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

Vrabič N, Fakin A, Tekavčič Pompe M
J Fr Ophtalmol 2024 Oct;47(8):104232. Epub 2024 Aug 29 doi: 10.1016/j.jfo.2024.104232. PMID: 39213781
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

Clinical prediction guides

Vrabič N, Fakin A, Tekavčič Pompe M
J Fr Ophtalmol 2024 Oct;47(8):104232. Epub 2024 Aug 29 doi: 10.1016/j.jfo.2024.104232. PMID: 39213781
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
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
Sekiya K, Nakazawa M, Tanaka H
Jpn J Ophthalmol 2001 Nov-Dec;45(6):636-9. doi: 10.1016/s0021-5155(01)00424-5. PMID: 11754908

Recent systematic reviews

Vrabič N, Fakin A, Tekavčič Pompe M
J Fr Ophtalmol 2024 Oct;47(8):104232. Epub 2024 Aug 29 doi: 10.1016/j.jfo.2024.104232. PMID: 39213781

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