Table 2.

Monogenic Renal Disorders in the Differential Diagnosis of Nephronophthisis-Related Ciliopathies

GeneDisorderMOIKey Features
Tubulointerstitial kidney diseases
HNF1B ADTKD-HNF1BADTubulointerstitial kidney disease & variable other manifestations incl MODY, hyperuricemia & gout, hypomagnesemia, CKD, CAKUT, & unexplained liver function abnormalities
MUC1 ADTKD-MUC1 ADSlowly progressive tubulointerstitial disease that leads to ESKD & need for dialysis or kidney transplantation. The rate of loss of kidney function is variable w/in & between families, w/median age of onset of 46 yrs. There are no other systemic manifestations.
REN ADTKD-REN ADChildhood/adolescent onset, the more common presentation of ADTKD-REN, is characterized by ↓ estimated glomerular filtration rate, acidosis, hyperkalemia, & anemia early in life, followed by slowly progressive CKD & gout. Adult onset, the less common presentation, is characterized by gout or mild, slowly progressive CKD beginning in the 3rd decade. Anemia, hyperkalemia, & acidemia do not occur.
SEC61A1 ADTKD-SEC61A1ADTubulointerstitial kidney disease, slowly progressive CKD, leukopenia, abscess formation, IUGR, & postnatal growth restriction (See ADTKD-UMOD.)
UMOD ADTKD-UMOD ADNormal urinalysis & slowly progressive CKD, usually 1st noted in teenage yrs & progressing to ESKD between 3rd & 7th decades. Hyperuricemia is often present from an early age & gout occurs in teenage yrs in ~8% of affected persons & develops in 55% of affected persons over time.
Cystic kidney diseases
PKHD1 ARPKD ARARPKD belongs to a group of congenital hepatorenal fibrocystic syndromes & is a cause of significant renal- & liver-related morbidity & mortality in children. It typically presents in neonatal period w/enlarged echogenic kidneys. Renal disease is characterized by nephromegaly, hypertension, & varying degrees of renal dysfunction. >50% of affected persons progress to ESKD w/in 1st decade of life.
ALG5 Atypical ADPKD (See ADPKD.)
Note: In atypical ADPKD, kidneys are usually not as enlarged as in ADPKD.		ADNormal-sized kidneys, characterized by multiple small kidney cysts, progressive interstitial fibrosis, & late-onset ESKD (range: age 62-91 yrs); few or no liver cysts 1
ALG9 ADNormal-sized to mildly enlarged kidneys, multiple kidney cysts, occasional late-onset CKD, w/or w/out liver cysts 2
DNAJB11 ADNormal-sized kidneys w/bilateral small cysts, occasional liver cysts, progressive tubulointerstitial fibrosis, & late-onset ESKD (range: age 59-89 yrs) 3
GANAB ADKidneys are normal-sized to mildly enlarged due to a few large cysts, mild chronic kidney disease and polycystic liver disease of variable severity. 4
IFT140 ADEnlarged kidneys, few large cysts, mild & late-onset CKD, few liver cysts 5
Other
COL4A3
COL4A4
COL4A5 		Alport syndrome XL
AR
AD		Phenotypes range from progressive renal disease w/extrarenal abnormalities (ocular & hearing) to isolated hematuria w/non-progressive or very slowly progressive course. In XL Alport syndrome (XLAS), disease manifestations are typically more severe in affected males. In the absence of treatment, renal disease progresses from microscopic hematuria to proteinuria, progressive renal insufficiency, & ESKD in males w/XLAS & persons w/AR Alport syndrome. However, affected females w/XLAS or persons w/AD Alport syndrome may have severe involvement as well. Progressive SNHL is usually present by late childhood / early adolescence. Ocular findings incl anterior lenticonus, maculopathy, corneal endothelial vesicles, & recurrent corneal erosion.
SLC41A1 NPH-like nephropathy 2 (OMIM 619468)ARTubulointerstitial kidney disease w/histologic & ultrasound changes characteristic of NPH 6
XPNPEP3 NPH-like nephropathy 1 (OMIM 613159)ARTubulointerstitial kidney disease w/histologic & ultrasound changes characteristic of NPH. Extrarenal manifestations can incl signs of mitochondriopathy (e.g., neurologic signs, hearing loss). 7

AD = autosomal dominant; ADTKD = autosomal dominant tubulointerstitial kidney disease; AR = autosomal recessive; ARPKD = autosomal recessive polycystic kidney; CAKUT = congenital anomalies of the kidneys and urinary tract; CKD = chronic kidney disease; ESKD = end-stage kidney disease; MODY = maturity-onset diabetes of the young; MOI = mode of inheritance; NPH = nephronophthisis; SNHL = sensorineural hearing loss; XL = X-linked

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From: Nephronophthisis-Related Ciliopathies

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