Renal cysts and diabetes syndrome

General Information (adopted from Orphanet):

Synonyms, Signs: RCAD
MODY5
Glomerulocystic kidney disease, hypoplastic type
Maturity-onset diabetes of the young, type 5
Renal cysts - maturity-onset diabetes of the young
FJHN, atypical
Glomerulocystic kidney, familial hypoplastic
Hyperuricemic nephropathy, familial juvenile, atypical
Renal dysfunction - early-onset diabetes
RCAD syndrome
Number of Symptoms 81
OrphanetNr: 93111
OMIM Id: 137920
ICD-10: E11.2
UMLs:
MeSH:
MedDRA:
Snomed:

Prevalence, inheritance and age of onset:

Prevalence: < 0.9 of 100 000
Inheritance: Autosomal dominant
23869298 [IBIS]
Age of onset: Adolescent
Adult
23869298 [IBIS]

Disease classification (adopted from Orphanet):

Parent Diseases: Rare genetic diabetes mellitus
 -Rare genetic disease
Rare insulin-independent diabetes mellitus
 -Rare endocrine disease
Syndromic renal or urinary tract malformation
 -Rare developmental defect during embryogenesis
 -Rare genetic disease
 -Rare renal disease

Comment:

Caused by a mutation in the gene encoding hepatocyte nuclear factor-1-beta (HNF1B or TCF2) (OMIM). About 1% of all MODY cases (PMID:25360493). The clinical diagnosis of RCAD is complicated by incomplete penetrance and a high degree of de novo cases (50–60%) (PMID:25360493). The severity of the renal disease associated with HNF1B mutations was extremely variable (from prenatal renal failure to normal renal function in adulthood) and was not correlated with the genotype (PMID:20378641).

Symptom Information: Sort by abundance 

1
 (HPO:0000083) Renal insufficiency 20378641; 9703339 IBIS 232 / 7739
2
 (HPO:0000008) Abnormality of female internal genitalia Occasional [Orphanet] 23878349 IBIS 3 / 7739
3
 (HPO:0001919) Acute kidney injury 25441779; 20378641 IBIS 21 / 7739
4
 (HPO:0000107) Renal cyst Very frequent [IBIS] 19/23 [HPO] 23878349; 25441779; 20378641; 15930087; 11562418; 9703339; 12161522 IBIS 126 / 7739
5
 (HPO:0003076) Glycosuria 21767339 IBIS 32 / 7739
6
 (HPO:0000112) Nephropathy Very frequent [IBIS] Very frequent [Orphanet] 20378641 IBIS 92 / 7739
7
 (HPO:0000013) Hypoplasia of the uterus 23878349; 23869298 IBIS 21 / 7739
8
 (HPO:0012210) Abnormal renal morphology 23878349; 25441779 IBIS 18 / 7739
9
 (HPO:0005576) Tubulointerstitial fibrosis 15068978 IBIS 32 / 7739
10
 (HPO:0000089) Renal hypoplasia Occasional [Orphanet] 1/23 [HPO] 21767339; 25441779; 20378641 IBIS 78 / 7739
11
 (HPO:0012622) Chronic kidney disease 20378641 IBIS 32 / 7739
12
 (HPO:0010946) Dilatation of the renal pelvis 25441779; 20378641 IBIS 2 / 7739
13
 (HPO:0003774) Stage 5 chronic kidney disease 20378641; 9703339; 12675839 IBIS 78 / 7739
14
 (HPO:0012584) Bilateral renal hypoplasia 12161522 IBIS 2 / 7739
15
 (HPO:0000027) Azoospermia 15068978 IBIS 28 / 7739
16
 (HPO:0000137) Abnormality of the ovary 15930087 IBIS 41 / 7739
17
 (HPO:0004719) Hyperechogenic kidneys 25360493; 20378641; 12148114 IBIS 10 / 7739
18
 (HPO:0004734) Renal cortical microcysts 20378641 IBIS 10 / 7739
19
 (HPO:0011130) Abnormality of renal calyx morphology 25441779 IBIS 2 / 7739
20
 (HPO:0000813) Bicornuate uterus 23878349; 23869298; 20378641; 15068978; 11918730; 11317673 IBIS 22 / 7739
21
 (HPO:0100611) Multiple glomerular cysts 23878349; 25360493 IBIS 2 / 7739
22
 (HPO:0000078) Abnormality of the genital system 25360493; 15068978 IBIS 33 / 7739
23
 (HPO:0003762) Uterus didelphys 20378641; 15930087; 11918730 IBIS 8 / 7739
24
 (HPO:0000122) Unilateral renal agenesis 20378641; 11918730 IBIS 24 / 7739
25
 (HPO:0012243) Abnormal genital system morphology 15930087 IBIS 1 / 7739
26
 (HPO:0012583) Unilateral renal hypoplasia 20378641; 12148114 IBIS 1 / 7739
27
 (HPO:0002048) Renal cortical atrophy 15068978 IBIS 3 / 7739
28
 (HPO:0000110) Renal dysplasia Very frequent [Orphanet] hallmark [HPO] 23878349; 25360493 IBIS 44 / 7739
29
 (HPO:0012608) Hypermagnesiuria 19389850 IBIS 3 / 7739
30
 (HPO:0000798) Oligospermia 15068978 IBIS 13 / 7739
31
 (HPO:0000003) Multicystic kidney dysplasia Very frequent [IBIS] Very frequent [Orphanet] 23878349; 23869298 IBIS 17 / 7739
32
 (HPO:0000130) Abnormality of the uterus Occasional [Orphanet] 23878349; 23869298; 20378641 IBIS 86 / 7739
33
 (HPO:0000047) Hypospadias Occasional [Orphanet] 11918730 IBIS 250 / 7739
34
 (HPO:0000103) Polyuria Occasional [Orphanet] 15068978; 11317673 IBIS 60 / 7739
35
 (HPO:0000081) Duplicated collecting system 25441779 IBIS 16 / 7739
36
 (HPO:0000074) Ureteropelvic junction obstruction 20378641; 12675839 IBIS 15 / 7739
37
 (HPO:0000800) Cystic renal dysplasia Very frequent [IBIS] Very frequent [Orphanet] 23878349 IBIS 31 / 7739
38
 (HPO:0000022) Abnormality of male internal genitalia Occasional [Orphanet] 15068978 IBIS 5 / 7739
39
 (HPO:0000097) Focal segmental glomerulosclerosis 25441779 IBIS 37 / 7739
40
 (HPO:0000113) Polycystic kidney dysplasia Very frequent [Orphanet] hallmark [HPO] 23878349; 23869298; 25360493 IBIS 75 / 7739
41
 (HPO:0000787) Nephrolithiasis 25441779; 12675839 IBIS 78 / 7739
42
 (HPO:0004727) Impaired renal concentrating ability 12161522 IBIS 6 / 7739
43
 (HPO:0003250) Aplasia of the vagina 23878349 IBIS 6 / 7739
44
 (HPO:0000093) Proteinuria 25441779; 9703339 IBIS 169 / 7739
45
 (HPO:0000095) Abnormality of the glomerulus 15068978 IBIS 1 / 7739
46
 (HPO:0012213) Decreased glomerular filtration rate 20378641 IBIS 21 / 7739
47
 (HPO:0000151) Aplasia of the uterus 20378641 IBIS 12 / 7739
48
 (HPO:0000148) Vaginal atresia 20378641 IBIS 16 / 7739
49
 (HPO:0009715) Papillary cystadenoma of the epididymis 15068978 IBIS 3 / 7739
50
 (HPO:0000085) Horseshoe kidney Occasional [Orphanet] 23878349; 25441779; 11845237 IBIS 39 / 7739
51
 (HPO:0001959) Polydipsia 11317673 IBIS 43 / 7739
52
 (HPO:0001249) Intellectual disability Occasional [Orphanet] 20378641 IBIS 1089 / 7739
53
 (HPO:0001953) Diabetic ketoacidosis 25441779; 15068978 IBIS 6 / 7739
54
 (HPO:0009800) Maternal diabetes 11562418 IBIS 14 / 7739
55
 (HPO:0005978) Type II diabetes mellitus 21767339; 20378641; 15068978; 15930087 IBIS 68 / 7739
56
 (HPO:0004904) Maturity-onset diabetes of the young 23878349; 21767339; 20378641; 15930087; 9703339; 12161522; 12148114; 11845237; 11317673; 15001636 IBIS 17 / 7739
57
 (HPO:0001997) Gout 23878349; 12675839 IBIS 18 / 7739
58
 (HPO:0005236) Chronic calcifying pancreatitis 25441779 IBIS 2 / 7739
59
 (HPO:0002594) Pancreatic hypoplasia Occasional [Orphanet] 5/6 [HPO] 25360493; 21767339; 20378641 IBIS 5 / 7739
60
 (HPO:0012094) Abnormal pancreas size 25441779 IBIS 5 / 7739
61
 (HPO:0012093) Abnormality of endocrine pancreas physiology 23869298 IBIS 4 / 7739
62
 (HPO:0001396) Cholestasis Occasional [Orphanet] 15068978; 15001636 IBIS 136 / 7739
63
 (HPO:0001410) Decreased liver function 25360493; 12148114 IBIS 59 / 7739
64
 (HPO:0012092) Abnormality of exocrine pancreas physiology Occasional [Orphanet] 25360493; 15068978 IBIS 9 / 7739
65
 (HPO:0001397) Hepatic steatosis Occasional [Orphanet] 21767339 IBIS 75 / 7739
66
 (HPO:0001738) Exocrine pancreatic insufficiency Occasional [Orphanet] 23869298; 25360493 IBIS 23 / 7739
67
 (HPO:0002910) Elevated hepatic transaminases Occasional [Orphanet] 21767339; 20378641 IBIS 158 / 7739
68
 (HPO:0008897) Postnatal growth retardation 21767339 IBIS 113 / 7739
69
 (HPO:0001518) Small for gestational age 23878349 IBIS 107 / 7739
70
 (HPO:0001511) Intrauterine growth retardation 25360493; 21767339 IBIS 358 / 7739
71
 (HPO:0012465) Elevated hepatic iron concentration 21767339 IBIS 8 / 7739
72
 (HPO:0002902) Hyponatremia 25441779 IBIS 37 / 7739
73
 (HPO:0003259) Elevated serum creatinine 23878349 IBIS 31 / 7739
74
 (HPO:0002917) Hypomagnesemia 23878349; 19389850 IBIS 19 / 7739
75
 (HPO:0001946) Ketosis 15068978 IBIS 17 / 7739
76
 (HPO:0002149) Hyperuricemia Occasional [Orphanet] 23878349; 20378641; 12675839 IBIS 37 / 7739
77
 (OMIM) Enlarged glomeruli 15068978 IBIS 3 / 7739
78
 (OMIM) Unicornuate uterus 15930087 IBIS 3 / 7739
79
 (MedDRA:10062190) Metabolic encephalopathy 25441779 IBIS 1 / 7739
80
 (OMIM) Oligomeganephronia 15068978 IBIS 1 / 7739
81
 (OMIM) Atresia of the vas deferens 15068978 IBIS 1 / 7739

Associated genes:

HNF1B;

ClinVar (via SNiPA)

Gene symbol Variation Clinical significance Reference

Additional Information:

Description: (OMIM) The 'renal cysts and diabetes syndrome' is an autosomal dominant disorder comprising (1) nondiabetic renal disease resulting from abnormal renal development, and (2) diabetes, which in some cases occurs earlier than age 25 years and is thus consistent ...
Clinical Description OMIM Horikawa et al. (1997) reported a Japanese family in which 3 sibs developed MODY at ages 14, 10, and 15 years, respectively. Their mother and maternal uncle developed diabetes at ages 40 and 60, respectively; their father developed ...
Genotype-Phenotype Correlations OMIM Lindner et al. (1999) noted that heterozygous mutations in the TCF1 (142410) and TCF2 genes can cause MODY3 (600496) and MODY5, respectively. In addition to effects on beta-cell function, deficiency of either TCF1 or TCF2 affects renal function. ...
Molecular genetics OMIM In 2 Japanese sibs with a phenotype consistent with renal cysts and diabetes syndrome, Horikawa et al. (1997) identified a heterozygous mutation in the TCF2 gene (189907.0001). The sibs developed diabetes mellitus at ages 10 and 15 years, ...