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Senior-Løken Syndrome

Senior-Loken Syndrome

Senior Loken syndrome is an autosomal recessive disease that is very rare and has oculo-renal features that include chronic renal disease and retinal dystrophy.


Presentation

The two major components of Senior Loken syndrome (SLS) are the early onset of retinal degeneration named Leber congenital amaurosis and a cystic kidney disease known as nephronophthisis [1].

Nephronophthisis (NPHP)

Nephronophthisis has an insidious onset and results from mutations in the NPHP genes. The ensuing tubulointerstitial nephritis can induce acute or chronic renal insufficiency and subsequently progress to end-stage kidney disease before the age of 20. Most patients present when the renal failure is in an advanced stage [2][3].

Depending on the onset of end-stage kidney disease, nephronophthisis has been divided into three clinical variants: infantile, juvenile, and adolescent [4].

The earliest symptoms are mild and can manifest in infancy or childhood as polyuria, polydipsia, secondary enuresis due to an impaired concentrating ability, and anemia. Additional features that may be observed include neurological disorders, liver fibrosis, and obesity.

Ocular manifestations

There are variable retinal lesions in Senior Loken syndrome, from Leber congenital amaurosis to retinitis pigmentosa [5].

Leber congenital amaurosis is a severe retinal dystrophy leading to blindness during infancy, diffuse atypical pigmentation of the retina, nystagmus, and optic disc pallor.

Retinitis pigmentosa initially presents as night blindness (nyctalopia) slowly progressing to a considerable loss of peripheral visual field (tunnel vision) and finally to a complete absence of light perception. Cone function and central visual acuity are maintained until a late stage of the disease. A number of other ocular manifestations have been observed in Senior Loken syndrome including keratoconus, cataract, retinitis punctata albescens, and Coat's disease [6].

Refractory Anemia
  • Congenital medullary cystic disease of the kidney with severe refractory anemia. Am J Dis Child 1945; 69: 369–377. Google Scholar 2. Fanconi G, Hanhart E, von Albertini A, Euhlinger R, Dolivo G, Prader A. Die familiäre juvenile Nephronophthise.[link.springer.com]
  • Congenital medullary cysts of the kidneys with severe refractory anemia. Am. J. Dis. Child. 69, 369–377 (1945). 2 Fanconi, G., Hanhart, E. & Albertini, A. Die familiäre juvenile Nephronophthise. Hel. Pediatr. Acta 6, 1–49 (1951). 3 Hildebrandt, F.[doi.org]
  • Congenital medullary cysts of the kidneys with severe refractory anemia . Am. J. Dis. Child. 69 , 369–377 (1945). 2. Fanconi, G. , Hanhart, E. & Albertini, A. Die familiäre juvenile Nephronophthise . Hel. Pediatr. Acta 6 , 1–49 (1951). 3.[nature.com]
Camping
  • (PDF 159 kb) Further reading Sensory primary cilium is a responsive cAMP microdomain in renal epithelia Rinzhin T. Sherpa, Ashraf M. Mohieldin, Rajasekharreddy Pala, Dagmar Wachten, Rennolds S. Ostrom & Surya M.[doi.org]
  • […] septum development protein binding cytosol cilium cilium lipid metabolic process establishment or maintenance of cell polarity determination of left/right symmetry Wnt signaling pathway extracellular matrix organization lung development regulation of cAMP[atlasgeneticsoncology.org]
Fishing
  • FISH Probe Protocols Protocol, Procedure, or Form Name Last Modified Download Scientific Citations There are currently no FISH related citations for this gene.[empiregenomics.com]
Failure to Thrive
  • Common findings include a failure to thrive and weakness. Anorexia, nausea, pruritus, bone pain, and neurologic symptoms herald ESRD. Because of salt wasting, hypertension is rare, except in the infantile form of nephronophthisis.[emedicine.medscape.com]
  • […] to thrive Microphthalmia Oxycephaly Craniosynostosis Meningocele Abnormal retinal morphology Esotropia Glycosuria Renal cortical cysts Wide anterior fontanel Hypoplasia of the brainstem Trigonocephaly Dilatation Cryptorchidism Short neck Agenesis of[mendelian.co]
  • Failure to thrive (Infantile dermatitis) 138. Leopard syndrome • L Lentigenes • E Ecg abnormalities - Bundle Branch Block 7.[de.slideshare.net]
Abdominal Tenderness
  • He had abdominal tenderness without guarding. Investigations revealed a lipase level of 3856 I U/l and an abdominal CT scan showed features of acute pancreatitis.[ncbi.nlm.nih.gov]
Heart Murmur
  • Also at this time we had a heart murmur that needed to be evaluated. That turned out to be aortic stenosis, a congenital heart defect. Bradley was diagnosed with bipolar disorder when he was 7.[inspire.com]
Loss of Peripheral Vision
  • Symptoms of RP range in age of onset and severity, and may include night blindness, progressive loss of peripheral vision, and eventual loss of central vision, leading to blindness. [3] [4] In rare cases, additional symptoms such as liver fibrosis or[rarediseases.info.nih.gov]
Retinal Lesion
  • Ocular manifestations There are variable retinal lesions in Senior Loken syndrome, from Leber congenital amaurosis to retinitis pigmentosa.[symptoma.com]
  • Retinal lesions are variable, ranging from severe Leber congenital amaurosis ( LCA ), which can cause blindness in early infancy, to later onset retinitis pigmentosa (RP). Other ocular symptoms can include cataract, Coat’s disease, and keratoconus.[invitae.com]
Progressive Loss of Vision
  • Unlike Usher Syndrome, where a progressive loss of vision is typical, vision loss in individuals with LCA usually remains stable through young adult life. Progression of vision loss later in life has not yet been clearly defined.[tsbvi.edu]
Involuntary Movements
  • This condition causes vision problems, including an increased sensitivity to light (photophobia), involuntary movements of the eyes (nystagmus), and extreme farsightedness ( hyperopia ).[ghr.nlm.nih.gov]
  • LCA causes vision problems such as sensitivity to light (photophobia), involuntary movements (nystagmus), and severe farsightedness (hyperopia).[rarediseases.org]
Kidney Failure
  • Fatigue and anemia from the progressive kidney failure are common problems. Medical description: A number of renal-retinal disorders have been reported and the nosology is not clear.[wohproject.org]
  • failure * Metabolic acidosis * Growth retardation * Renal salt wasting * Tapetoretinal degeneration * Retinitis pigmentosa Causes - Senior Loken Syndrome Not supplied.[checkorphan.org]
  • Keywords: Chromosome Mapping, Chronic Kidney Failure, Consanguinity, Genetic Markers, Haplotypes, Homozygote, Human Pair 1 Chromosomes, Lod Score, Microsatellite Repeats, Pedigree, Retinitis Pigmentosa, Software, Syndrome Source: American Journal of Human[edoc.mdc-berlin.de]
  • Some of these include: Excessive urination (polyuria) Inability to concentrate urine Renal salt wasting Thirst Kidney failure Arterial hypertension (high blood pressure) Anemia Metabolic acidosis Thickening of kidney filtration tissues Increased blood[disabilitycasereview.com]
  • Eventually the patient may have symptoms such as nausea, vomiting, weight loss, fatigue, anemia and ultimately kidney failure.[rarediseases.org]

Workup

The diagnosis of Senior Loken syndrome is based on the clinical presentation of retinopathy and chronic interstitial nephritis. A complete workup of the organs involved is recommended, consisting of renal evaluation (urinalysis, renal function tests, abdominal ultrasound) and ophthalmologic tests (visual acuity, color vision, fundoscopy, refraction defects, ocular movements, electroretinogram). The liver should be assessed by liver function tests and ultrasound to exclude hepatic fibrosis. In addition, a neurological examination is recommended in infants.

On ultrasonography, the kidneys may show an increase in the echogenicity of renal parenchyma, cysts in a poorly differentiated corticomedullary junction or medullary cysts. These findings may eventually progress to more notable cysts and atrophy of the kidneys. A normal ultrasound appearance is possible in juvenile nephronophthisis but the diagnosis cannot be ruled out if medullary cysts are absent at the time of presentation [7].

A renal biopsy may reveal the triad of interstitial fibrosis, corticomedullary cysts, and disruption of the tubular basement membrane [8].

Genetic analysis is required to diagnose Senior Loken syndrome. The most common mutation in this disease is the deletion of the gene NPHP1. Nephronophthisis can be diagnosed by mutational screening and histological findings on renal biopsy. Mutations in nine genes are linked to retinal degeneration and mutated NPHP1 to NPHP13 genes result in nephronophthisis.

Hypertriglyceridemia
  • He had no family history of renal disease, hypertriglyceridemia or cholelithiasis. He presented to our center complaining of acute abdominal pain and vomiting. He had abdominal tenderness without guarding.[ncbi.nlm.nih.gov]
  • He had no family history of renal disease, hypertriglyceridemia or cholelithiasis. He had abdominal tenderness without guarding. Investigations revealed a lipase level of 3856 I U/l and an abdominal CT scan showed features of acute pancreatitis.[cags.org.ae]
Blood Urea Nitrogen Increased
  • urea nitrogen * Increased blood creatinine level * Thickening of kidney filtration tissues * Endstage kidney disease * Polyuria * Enuresis * Inability to concentrate urine * Kidney failure * Metabolic acidosis * Growth retardation * Renal salt wasting[checkorphan.org]
Blood Urea Nitrogen Increased
  • urea nitrogen * Increased blood creatinine level * Thickening of kidney filtration tissues * Endstage kidney disease * Polyuria * Enuresis * Inability to concentrate urine * Kidney failure * Metabolic acidosis * Growth retardation * Renal salt wasting[checkorphan.org]
Lymphocytic Infiltrate
  • A renal biopsy showed extensive interstitial fibrosis with focal lymphocytic infiltration. One individual had a mutlti-year history of diabetes insipidus and vision ‘problems’ before being diagnosed. Easy fatigability can be a chief complaint.[wohproject.org]

Treatment

  • Management and treatment Affected children should be regularly monitored by a pediatric nephrologist.[orpha.net]
  • There is currently no treatment to prevent or stop the progression of vision loss due to retinal dystrophy, but various low-vision aids may be helpful for those who have remaining vision. [3] Last updated: 4/13/2015[rarediseases.info.nih.gov]
  • Treatment: No treatment is available for the pigmentary retinopathy, but anemia and kidney failure are amenable to the usual therapies. Prognosis: Relatively good with survival to adulthood. Ancillary treatments and support: General supportive.[wohproject.org]

Prognosis

  • Prognosis Prognosis depends mostly on renal complications that represent the major cause of death if not timely diagnosed and managed.[orpha.net]
  • Prognosis - Senior Loken Syndrome Prognosis of Senior-Loken Syndrome: poor with death occurring before adulthood Treatment - Senior Loken Syndrome Not supplied. Resources - Senior Loken Syndrome Not supplied.[checkorphan.org]
  • Prognosis: Relatively good with survival to adulthood. Ancillary treatments and support: General supportive. Specialists and specialty centers: Ophthalmologist, Nephrologist, Internist. References: Schimke, R.N.: Hereditary renal-retinal dysplasia.[wohproject.org]

Etiology

  • Etiology SLSN is a genetically heterogeneous ciliopathy. Mutations in 7 different genes ( NPHP1, INVS, NPHP3, NPHP4, IQCB1, CEP290, SDCCAG8 ) have been described.[orpha.net]
  • Lyons, both globally recognized leaders, provide authoritative coverage of all the pediatric ophthalmic conditions you’re likely to encounter in practice, including the latest clinical advances in etiology, diagnosis, and medical and surgical management[books.google.com]
  • 11380932 ) microcephaly ( 11380932 ) skeletal anomalies cone epiphyses short stature kyphoscoliosis short metacarpals cutis laxa congenital hepatic fibrosis renal anomalies medullary cystic kidneys nephronophthisis vasopressin-resistant diabetes insipidus Etiology[humpath.com]

Epidemiology

  • Summary Epidemiology The worldwide prevalence is estimated at around 1/1,000,000.[orpha.net]
  • Relevant External Links for SDCCAG8 Genetic Association Database (GAD) SDCCAG8 Human Genome Epidemiology (HuGE) Navigator SDCCAG8 Atlas of Genetics and Cytogenetics in Oncology and Haematology: SDCCAG8 No data available for Genatlas for SDCCAG8 Gene Candidate[genecards.org]
  • […] recessive and patients develop end-stage renal failure (ESRF) by adolescence. [ 1, 2 ] The protein products, named nephrocystins, which become abnormal in this disorder, have primarily a function in cilial structures (making it a ' ciliopathy '). [ 3 ] Epidemiology[patient.info]
Sex distribution
Age distribution

Pathophysiology

  • Comprehensively updated to reflect everything you need to know regarding retinal diagnosis, treatment, development, structure, function, and pathophysiology, this monumental ophthalmology reference work equips you with expert answers to virtually any[books.google.com]

Prevention

  • There is currently no treatment to prevent or stop the progression of vision loss due to retinal dystrophy, but various low-vision aids may be helpful for those who have remaining vision. [3] Last updated: 4/13/2015[rarediseases.info.nih.gov]
  • Prevention - Senior Loken Syndrome Not supplied. Diagnosis - Senior Loken Syndrome Not supplied.[checkorphan.org]
  • No treatment is currently available to prevent progression to visual loss. Prognosis Prognosis depends mostly on renal complications that represent the major cause of death if not timely diagnosed and managed.[orpha.net]
  • To date, no definite treatment is available to prevent progression to visual loss. Qatar Othman et al. (2012) described two sisters with Senior Loken syndrome.[cags.org.ae]

References

Article

  1. Hildebrandt F, Zhou W. Nephronophthisis-associated ciliopathies. J Am Soc Nephrol. 2007;18(6):1855–1871.
  2. Otto EA, Tory K, Attanasio M, et al. Hypomorphic mutations in meckelin (MKS3/TMEM67) cause nephronophthisis with liver fibrosis (NPHP11) J Med Genet. 2009;46:663–70.
  3. Godel V, Iaina A, Nemet P, Lazar M. Sector retinitis pigmentosa in juvenile nephronophthisis. Br J Ophthalmol. 1980;64:124–6.
  4. Salomon R, Saunier S, Niaudet P. Nephronophthisis. Pediatr Nephrol. 2009;24:2333–44.
  5. Satran D, Pierpont ME, Dobyns WB. Cerebello-oculo-renal syndromes including Arima, Senior Loken and COACH syndromes: More than just variants of Joubert syndrome. Am J Med Genet A. 1999;86:459–69.
  6. Gleeson JG, Keeler LC, Parisi MA, et al. Molar tooth sign of the midbrain-hindbrain junction: Occurrence in multiple distinct syndromes. Am J Med Genet A. 2004;125:125–34.
  7. Blowey DL, Querfeld U, Geary D, Warady BA, Alon U. Ultrasound findings in juvenile nephronophthisis. Pediatr Nephrol. 1996;10:22–4.
  8. Aguilera A, Rivera M, Gallego N, Nogueira J, Ortuno J. Sonographic appearance of the juvenile nephronophthisis-cystic renal medulla complex. Nephrol Dial Transplant. 1997;12:625–26.

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Last updated: 2019-07-11 20:56