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Nephrotic syndrome 14(NPHS14; SPLIS; RENI)

MedGen UID:
1617660
Concept ID:
C4540559
Disease or Syndrome
Synonyms: RENAL, ENDOCRINE, NEUROLOGIC, AND IMMUNE SYNDROME; RENI SYNDROME
 
Gene (location): SGPL1 (10q22.1)
 
Monarch Initiative: MONDO:0033203
OMIM®: 617575
Orphanet: ORPHA506334

Disease characteristics

Sphingosine phosphate lyase insufficiency syndrome (SPLIS) is characterized by varying combinations of steroid-resistant nephrotic syndrome (ranging from nonimmune fetal hydrops to adolescent onset), primary adrenal insufficiency (with or without mineralocorticoid deficiency), testicular insufficiency, hypothyroidism, ichthyosis, lymphopenia/immunodeficiency, and neurologic abnormalities that can include developmental delay, regression / progressive neurologic involvement, cranial nerve deficits, and peripheral motor and sensory neuropathy. [from GeneReviews]
Authors:
Kathryn Nicole Weaver  |  Bonnie Sullivan  |  Friedhelm Hildebrandt, et. al.   view full author information

Additional description

From OMIM
RENI syndrome (RENI) is an autosomal recessive form of steroid-resistant nephrotic syndrome with multisystemic manifestations. Most affected individuals present in infancy or early childhood with progressive renal dysfunction associated with focal segmental glomerulosclerosis (FSGS), resulting in end-stage renal disease within a few years. Other infants present with primary adrenal insufficiency. Some patients present in utero with fetal hydrops and fetal demise. Additional features of the disorder may include ichthyosis, acanthosis, adrenal insufficiency, immunodeficiency, and neurologic defects. In rare cases, patients present with isolated primary adrenal insufficiency (summary by Prasad et al., 2017; Lovric et al., 2017; Yang et al., 2023). For a discussion of genetic heterogeneity of nephrotic syndrome and FSGS, see NPHS1 (256300).  http://www.omim.org/entry/617575

Clinical features

From HPO
Cryptorchidism
MedGen UID:
8192
Concept ID:
C0010417
Congenital Abnormality
Cryptorchidism, or failure of testicular descent, is a common human congenital abnormality with a multifactorial etiology that likely reflects the involvement of endocrine, environmental, and hereditary factors. Cryptorchidism can result in infertility and increases risk for testicular tumors. Testicular descent from abdomen to scrotum occurs in 2 distinct phases: the transabdominal phase and the inguinoscrotal phase (summary by Gorlov et al., 2002).
Focal segmental glomerulosclerosis
MedGen UID:
4904
Concept ID:
C0017668
Disease or Syndrome
Segmental accumulation of scar tissue in individual (but not all) glomeruli.
Nephrotic syndrome
MedGen UID:
10308
Concept ID:
C0027726
Disease or Syndrome
Nephrotic syndrome is a collection of findings resulting from glomerular dysfunction with an increase in glomerular capillary wall permeability associated with pronounced proteinuria. Nephrotic syndrome refers to the constellation of clinical findings that result from severe renal loss of protein, with Proteinuria and hypoalbuminemia, edema, and hyperlipidemia.
Proteinuria
MedGen UID:
10976
Concept ID:
C0033687
Finding
Increased levels of protein in the urine.
Diffuse mesangial sclerosis
MedGen UID:
78698
Concept ID:
C0268747
Disease or Syndrome
Diffuse sclerosis of the mesangium, as manifestated by diffuse mesangial matrix expansion.
Steroid-resistant nephrotic syndrome
MedGen UID:
588369
Concept ID:
C0403397
Disease or Syndrome
A form of nephrotic syndrome that does not respond to treatment with steroid medication, defined as persistent proteinuria despite 60mg/m2 or 2mg/kg for 8 weeks, after insuring no infection or non-adherence to medication.
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.
Podocyte foot process effacement
MedGen UID:
481733
Concept ID:
C3280103
Finding
An anomaly of podocyte morphology characterized by the loss of the interdigitating foot process pattern (generally called foot process effacement; FPE). The term FPE designates the loss of the usual interdigitating pattern of foot processes of neighboring podocytes, leading to relatively broad expanses of podocyte processes covering the glomerular basement membrane (GBM). It is widely viewed as a pathological derangement that is associated with leakage of macromolecules such as albumin through the glomerular filtration barrier.
Mesangial hypercellularity
MedGen UID:
924090
Concept ID:
C4281741
Cell or Molecular Dysfunction
Increased numbers of mesangial cells per glomerulus, defined as more than 3 nuclei fully surrounded by matrix in one or more mesangial areas, not including perihilar region, on a standard 3-micron-thick tissue section, best evaluated on periodic acid-Schiff (PAS) stain.
Micropenis
MedGen UID:
1633603
Concept ID:
C4551492
Congenital Abnormality
Abnormally small penis. At birth, the normal penis is about 3 cm (stretched length from pubic tubercle to tip of penis) with micropenis less than 2.0-2.5 cm.
Sensorineural hearing loss disorder
MedGen UID:
9164
Concept ID:
C0018784
Disease or Syndrome
A type of hearing impairment in one or both ears related to an abnormal functionality of the cochlear nerve.
Cerebellar ataxia
MedGen UID:
849
Concept ID:
C0007758
Disease or Syndrome
Cerebellar ataxia refers to ataxia due to dysfunction of the cerebellum. This causes a variety of elementary neurological deficits including asynergy (lack of coordination between muscles, limbs and joints), dysmetria (lack of ability to judge distances that can lead to under- or overshoot in grasping movements), and dysdiadochokinesia (inability to perform rapid movements requiring antagonizing muscle groups to be switched on and off repeatedly).
Peripheral neuropathy
MedGen UID:
18386
Concept ID:
C0031117
Disease or Syndrome
Peripheral neuropathy is a general term for any disorder of the peripheral nervous system. The main clinical features used to classify peripheral neuropathy are distribution, type (mainly demyelinating versus mainly axonal), duration, and course.
Seizure
MedGen UID:
20693
Concept ID:
C0036572
Sign or Symptom
A seizure is an intermittent abnormality of nervous system physiology characterized by a transient occurrence of signs and/or symptoms due to abnormal excessive or synchronous neuronal activity in the brain.
Mental deterioration
MedGen UID:
66713
Concept ID:
C0234985
Mental or Behavioral Dysfunction
Loss of previously present mental abilities, generally in adults.
Global developmental delay
MedGen UID:
107838
Concept ID:
C0557874
Finding
A delay in the achievement of motor or mental milestones in the domains of development of a child, including motor skills, speech and language, cognitive skills, and social and emotional skills. This term should only be used to describe children younger than five years of age.
Developmental regression
MedGen UID:
324613
Concept ID:
C1836830
Disease or Syndrome
Loss of developmental skills, as manifested by loss of developmental milestones.
Generalized hypotonia
MedGen UID:
346841
Concept ID:
C1858120
Finding
Generalized muscular hypotonia (abnormally low muscle tone).
Microcephaly
MedGen UID:
1644158
Concept ID:
C4551563
Finding
Head circumference below 2 standard deviations below the mean for age and gender.
Lymphopenia
MedGen UID:
7418
Concept ID:
C0024312
Disease or Syndrome
A reduced number of lymphocytes in the blood.
Edema
MedGen UID:
4451
Concept ID:
C0013604
Pathologic Function
An abnormal accumulation of fluid beneath the skin, or in one or more cavities of the body.
Hypoglycemia
MedGen UID:
6979
Concept ID:
C0020615
Disease or Syndrome
A decreased concentration of glucose in the blood.
Hypoalbuminemia
MedGen UID:
68694
Concept ID:
C0239981
Finding
Reduction in the concentration of albumin in the blood.
Hypertriglyceridemia
MedGen UID:
167238
Concept ID:
C0813230
Finding
An abnormal increase in the level of triglycerides in the blood.
Ichthyosis
MedGen UID:
7002
Concept ID:
C0020757
Disease or Syndrome
An abnormality of the skin characterized the presence of excessive amounts of dry surface scales on the skin resulting from an abnormality of keratinization.
Hyperpigmentation of the skin
MedGen UID:
57992
Concept ID:
C0162834
Pathologic Function
A darkening of the skin related to an increase in melanin production and deposition.
Adrenal insufficiency
MedGen UID:
1351
Concept ID:
C0001623
Disease or Syndrome
Insufficient production of steroid hormones (primarily cortisol) by the adrenal glands.
Hypogonadism
MedGen UID:
5711
Concept ID:
C0020619
Disease or Syndrome
A decreased functionality of the gonad.
Hypothyroidism
MedGen UID:
6991
Concept ID:
C0020676
Disease or Syndrome
Deficiency of thyroid hormone.
Ptosis
MedGen UID:
2287
Concept ID:
C0005745
Disease or Syndrome
The upper eyelid margin is positioned 3 mm or more lower than usual and covers the superior portion of the iris (objective); or, the upper lid margin obscures at least part of the pupil (subjective).
Strabismus
MedGen UID:
21337
Concept ID:
C0038379
Disease or Syndrome
A misalignment of the eyes so that the visual axes deviate from bifoveal fixation. The classification of strabismus may be based on a number of features including the relative position of the eyes, whether the deviation is latent or manifest, intermittent or constant, concomitant or otherwise and according to the age of onset and the relevance of any associated refractive error.

Term Hierarchy

CClinical test,  RResearch test,  OOMIM,  GGeneReviews,  VClinVar  
  • CROGVNephrotic syndrome 14

Professional guidelines

PubMed

Angeletti A, Bruschi M, Kajana X, La Porta E, Spinelli S, Caridi G, Lugani F, Verrina EE, Ghiggeri GM
Front Immunol 2023;14:1213203. Epub 2023 Aug 29 doi: 10.3389/fimmu.2023.1213203. PMID: 37705972Free PMC Article
Agrawal S, Zaritsky JJ, Fornoni A, Smoyer WE
Nat Rev Nephrol 2018 Jan;14(1):57-70. Epub 2017 Nov 27 doi: 10.1038/nrneph.2017.155. PMID: 29176657Free PMC Article
Niaudet P, Broyer M
Pediatr Nephrol 2000 Aug;14(8-9):770-1. doi: 10.1007/pl00013434. PMID: 10955924

Recent clinical studies

Etiology

Podestà MA, Trillini M, Portalupi V, Gennarini A, Tomatis F, Villa A, Perna A, Rubis N, Remuzzi G, Ruggenenti P
Am J Kidney Dis 2024 Mar;83(3):340-349.e1. Epub 2023 Sep 29 doi: 10.1053/j.ajkd.2023.08.010. PMID: 37777061
Feng Z, Zhang Y, Lai Y, Jia C, Wu F, Chen D
Front Immunol 2023;14:1277554. Epub 2024 Jan 12 doi: 10.3389/fimmu.2023.1277554. PMID: 38283353Free PMC Article
Angeletti A, Bruschi M, Kajana X, La Porta E, Spinelli S, Caridi G, Lugani F, Verrina EE, Ghiggeri GM
Front Immunol 2023;14:1213203. Epub 2023 Aug 29 doi: 10.3389/fimmu.2023.1213203. PMID: 37705972Free PMC Article
Christian MT, Webb NJA, Mehta S, Woolley RL, Afentou N, Frew E, Brettell EA, Khan AR, Milford DV, Bockenhauer D, Saleem MA, Hall AS, Koziell A, Maxwell H, Hegde S, Prajapati H, Gilbert RD, Jones C, McKeever K, Cook W, Ives N
JAMA Pediatr 2022 Mar 1;176(3):236-243. doi: 10.1001/jamapediatrics.2021.5189. PMID: 34928294Free PMC Article
Agrawal S, Zaritsky JJ, Fornoni A, Smoyer WE
Nat Rev Nephrol 2018 Jan;14(1):57-70. Epub 2017 Nov 27 doi: 10.1038/nrneph.2017.155. PMID: 29176657Free PMC Article

Diagnosis

Feng Z, Zhang Y, Lai Y, Jia C, Wu F, Chen D
Front Immunol 2023;14:1277554. Epub 2024 Jan 12 doi: 10.3389/fimmu.2023.1277554. PMID: 38283353Free PMC Article
Al-Aubodah TA, Aoudjit L, Pascale G, Perinpanayagam MA, Langlais D, Bitzan M, Samuel SM, Piccirillo CA, Takano T
Nat Commun 2023 Nov 24;14(1):7682. doi: 10.1038/s41467-023-43504-8. PMID: 37996443Free PMC Article
Vincenti F, Angeletti A, Ghiggeri GM
Front Immunol 2023;14:1167741. Epub 2023 Jul 12 doi: 10.3389/fimmu.2023.1167741. PMID: 37503337Free PMC Article
Christian MT, Webb NJA, Mehta S, Woolley RL, Afentou N, Frew E, Brettell EA, Khan AR, Milford DV, Bockenhauer D, Saleem MA, Hall AS, Koziell A, Maxwell H, Hegde S, Prajapati H, Gilbert RD, Jones C, McKeever K, Cook W, Ives N
JAMA Pediatr 2022 Mar 1;176(3):236-243. doi: 10.1001/jamapediatrics.2021.5189. PMID: 34928294Free PMC Article
Salloum E, Khan KK, Cooper DL
Cancer 1997 Mar 1;79(5):1009-13. doi: 10.1002/(sici)1097-0142(19970301)79:5<1009::aid-cncr18>3.0.co;2-5. PMID: 9041164

Therapy

Podestà MA, Trillini M, Portalupi V, Gennarini A, Tomatis F, Villa A, Perna A, Rubis N, Remuzzi G, Ruggenenti P
Am J Kidney Dis 2024 Mar;83(3):340-349.e1. Epub 2023 Sep 29 doi: 10.1053/j.ajkd.2023.08.010. PMID: 37777061
Feng Z, Zhang Y, Lai Y, Jia C, Wu F, Chen D
Front Immunol 2023;14:1277554. Epub 2024 Jan 12 doi: 10.3389/fimmu.2023.1277554. PMID: 38283353Free PMC Article
Vincenti F, Angeletti A, Ghiggeri GM
Front Immunol 2023;14:1167741. Epub 2023 Jul 12 doi: 10.3389/fimmu.2023.1167741. PMID: 37503337Free PMC Article
Christian MT, Webb NJA, Mehta S, Woolley RL, Afentou N, Frew E, Brettell EA, Khan AR, Milford DV, Bockenhauer D, Saleem MA, Hall AS, Koziell A, Maxwell H, Hegde S, Prajapati H, Gilbert RD, Jones C, McKeever K, Cook W, Ives N
JAMA Pediatr 2022 Mar 1;176(3):236-243. doi: 10.1001/jamapediatrics.2021.5189. PMID: 34928294Free PMC Article
Agrawal S, Zaritsky JJ, Fornoni A, Smoyer WE
Nat Rev Nephrol 2018 Jan;14(1):57-70. Epub 2017 Nov 27 doi: 10.1038/nrneph.2017.155. PMID: 29176657Free PMC Article

Prognosis

Liu C, Shen J, Ding Z, Duan S, Dai E
Ren Fail 2024 Dec;46(2):2390558. Epub 2024 Aug 14 doi: 10.1080/0886022X.2024.2390558. PMID: 39143823Free PMC Article
Zonozi R, Laliberte K, Huizenga NR, Rosenthal JK, Jeyabalan A, Collins AB, Cortazar FB, Niles JL
Am J Kidney Dis 2021 Dec;78(6):793-803. Epub 2021 Jun 24 doi: 10.1053/j.ajkd.2021.04.014. PMID: 34174365
Zhao M, Veeranki SP, Magnussen CG, Xi B
BMJ 2020 Jul 1;370:m2031. doi: 10.1136/bmj.m2031. PMID: 32611588Free PMC Article
Sethi S, Madden BJ, Debiec H, Charlesworth MC, Gross L, Ravindran A, Hummel AM, Specks U, Fervenza FC, Ronco P
J Am Soc Nephrol 2019 Jun;30(6):1123-1136. Epub 2019 May 6 doi: 10.1681/ASN.2018080852. PMID: 31061139Free PMC Article
Dahan K, Debiec H, Plaisier E, Cachanado M, Rousseau A, Wakselman L, Michel PA, Mihout F, Dussol B, Matignon M, Mousson C, Simon T, Ronco P; GEMRITUX Study Group
J Am Soc Nephrol 2017 Jan;28(1):348-358. Epub 2016 Jun 27 doi: 10.1681/ASN.2016040449. PMID: 27352623Free PMC Article

Clinical prediction guides

Liu C, Shen J, Ding Z, Duan S, Dai E
Ren Fail 2024 Dec;46(2):2390558. Epub 2024 Aug 14 doi: 10.1080/0886022X.2024.2390558. PMID: 39143823Free PMC Article
Feng Z, Zhang Y, Lai Y, Jia C, Wu F, Chen D
Front Immunol 2023;14:1277554. Epub 2024 Jan 12 doi: 10.3389/fimmu.2023.1277554. PMID: 38283353Free PMC Article
Shi M, Wang Y, Zhang H, Ling Z, Chen X, Wang C, Liu J, Ma Y
Front Immunol 2023;14:1203062. Epub 2023 Sep 4 doi: 10.3389/fimmu.2023.1203062. PMID: 37731504Free PMC Article
Barry A, McNulty MT, Jia X, Gupta Y, Debiec H, Luo Y, Nagano C, Horinouchi T, Jung S, Colucci M, Ahram DF, Mitrotti A, Sinha A, Teeninga N, Jin G, Shril S, Caridi G, Bodria M, Lim TY, Westland R, Zanoni F, Marasa M, Turudic D, Giordano M, Gesualdo L, Magistroni R, Pisani I, Fiaccadori E, Reiterova J, Maringhini S, Morello W, Montini G, Weng PL, Scolari F, Saraga M, Tasic V, Santoro D, van Wijk JAE, Milošević D, Kawai Y, Kiryluk K, Pollak MR, Gharavi A, Lin F, Simœs E Silva AC, Loos RJF, Kenny EE, Schreuder MF, Zurowska A, Dossier C, Ariceta G, Drozynska-Duklas M, Hogan J, Jankauskiene A, Hildebrandt F, Prikhodina L, Song K, Bagga A, Cheong H 2nd, Ghiggeri GM, Vachvanichsanong P, Nozu K, Lee D, Vivarelli M, Raychaudhuri S, Tokunaga K, Sanna-Cherchi S, Ronco P, Iijima K, Sampson MG
Nat Commun 2023 Apr 29;14(1):2481. doi: 10.1038/s41467-023-37985-w. PMID: 37120605Free PMC Article
Salloum E, Khan KK, Cooper DL
Cancer 1997 Mar 1;79(5):1009-13. doi: 10.1002/(sici)1097-0142(19970301)79:5<1009::aid-cncr18>3.0.co;2-5. PMID: 9041164

Recent systematic reviews

Wang Z, Tang HY, Lin Q, Li XZ
BMC Nephrol 2023 May 1;24(1):120. doi: 10.1186/s12882-023-03160-y. PMID: 37127615Free PMC Article
Hahn D, Hodson EM, Craig JC
Cochrane Database Syst Rev 2023 Feb 28;2(2):CD005128. doi: 10.1002/14651858.CD005128.pub4. PMID: 36853224Free PMC Article
Pournasiri Z, Madani A, Nazarpack F, Sayer JA, Chavoshzadeh Z, Nili F, Tran P, Saba JD, Jamee M
World J Pediatr 2023 May;19(5):425-437. Epub 2022 Nov 12 doi: 10.1007/s12519-022-00615-4. PMID: 36371483
Dadgar K, Xue Y, Chung J, Sangar S, Bhatt M, Chan AKC, Geddie H, Chanchlani R
Pediatr Res 2023 May;93(6):1463-1469. Epub 2022 Sep 20 doi: 10.1038/s41390-022-02302-6. PMID: 36127405
Hodson EM, Sinha A, Cooper TE
Cochrane Database Syst Rev 2022 Feb 28;2(2):CD003233. doi: 10.1002/14651858.CD003233.pub3. PMID: 35224732Free PMC Article

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