Table 1.
Clinical presentations and genetic analyses of 12 affected family members
| Pt | Sex | eGFRa | HTNb | Microscopic hematuria b |
Proteinuriab,c | Kidney Morphology |
Myalgiab | Elevated CPKb,d |
CNS involvement | Cause of death |
Other conditionsb | Genetic resultsg |
Diagnosis |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| IV.1 | F | ESRD (71 y) | Y (50 y) | Y (70 y) | Y (70 y) | US at 71 y: atrophic RK (6.6 cm), 2 cysts in LK, 5 in RK | NA | NA | CSVD (CT scan, 71 y), TIA (36 y), recurrent ischemic strokes (70 y) | Stroke in 1995 (79 y | NA | NA | HANAC-like syndrome e |
| V.1 | F | 33 (67 y) | N (67 y) | Y (25 y) | Y (62 y): 0.7 | US at 59 y: atrophic RK (7.7cm), LK (9.3 cm), 2 cysts | Y (NA) | NA | Vertigo (64 y), normal non-enhanced CT (67 y) | - | Hypothyroidism (21 y), Gout (67 y) |
COL4A1: Q247* PKD2: WT |
HANAC-like syndrome |
| V.5 | M | 47 (67 y) | Y (57 y) | Y (14 y) | N (66 y) | MRI at 61 y: >15 cysts/kidney, no liver cyst, HtTKVf = 200 | Y (65 y) | NA | Migraines, dizzy spells since age 63; CSVD (MRI 58 y) | - | Gout (52 y), DM (65 y), Carotid endarteriectomy (57) |
COL4A1: Q247* PKD2: WT |
HANAC-like syndrome |
| VI.4 | M | 112 (32 y) | N (35 y) | Y (35 y) | N (35 y) | MRI at 35 y: 6 cysts in LK, 2 in RK | Y (32 y) | Y (32 y): 527 | Migraines since age 30, normal enhanced CT (32 y) | - | None | COL4A1: Q247* | HANAC-like syndrome |
| VII.1 | F | 129 (3 y) | N (4 y) | Y (3 y) | N (3 y) | NA | NA | NA | Global developmental delay, Hypotonia, absence epilepsy, MRI: thin cerebellar folia (4 y) | - | None | COL4A1: Q247* | COL4A1-related CNS disorder |
| III.2 | F | ESRD (48 y) | NA | NA | NA | NA | NA | ESRD (46 y) | NA | NA | Likely PKD2/COL4A1e | ||
| IV.3 | M | ESRD (51 y) | N (53 y) | Y (50 y) | Y (50 y) | Pyelography: enlarged kidneys, numerous renal cysts | Y (50 y) | NA | Migraines (50 y) | ESRD (51 y) | Tortuosity of the retinal arteries (50 y), Raynaud phenomena (50 y) | NA | Likely PKD2/COL4A1e |
| V.2 | M | ESRD (51 y) | Y (NA) | NA | NA | Non-enhanced CT at 56 y: Enlarged polycystic kidneys, polycystic liver | Y (56 y) | Y (55 y): 206 | Normal non-enhanced CT (56 y) | ID (57 y) | Gout (<50 y), hearing loss (56 y), aseptic necrosis of the femoral head (56 y), spontaneous cecum perforation (56 y) | NA | ADPKD-PKD2e; Possible PKD2/COL4A1 |
| V.4 | F | 30 (66 y) | N (59 y) | NA | N (59 y) | US: Enlarged polycystic kidneys, polycystic liver | N | NA | none | - | None |
PKD2: c.715_718dupTACG COL4A1: WT |
ADPKD-PKD2 |
| VI.1 | M | 21 (54 y) | Y (25 y) | N (55 y) | Y (53 y): 0.8 | MRI at 53 y: enlarged polycystic kidneys, HtTKVf=1953 | N | NA | none | - | T2DM (52 y); obesity, with BMI 40 kg/m2 |
PKD2: c.715_718dupTACG COL4A1: WT |
ADPKD-PKD2 |
| VI.2 | M | 56 (50 y) | Y (41 y) | NA | N (50 y) | MRI at 46 y: enlarged polycystic kidneys, HtTKVf=470 | N | NA | none | - | None |
PKD2: c.715_718dupTACG COL4A1: WT |
ADPKD-PKD2 |
| VI.3 | M | 36 (47 y) | Y (24 y) | N (47 y) | Y (34 y) | US at 31 y: LK 14.5 cm, LK 13.3 cm, >15 cysts/kidney | Y (47 y) | Y, under statins (33 y) | none | - | T1DM (11 y), MN (31 y) |
PKD2:c.715_718dupTACG COL4A1: WT |
ADPKD-PKD2 |
Expressed in mL/min/1.73 m2 on the basis of the last data available; obtained with the CKD-EPI equation for adults and with the Bedside Schwartz formula in the child.
Values in parentheses is age when first reported if present, or when last available data available if not present.
When available, proteinuria is expressed in grams per gram of urinary creatinine.
When available, expressed in UI/L
The patient is likely digenic carrier considering the familial history and the dominant inheritance of each condition.
Height adjusted total kidney volume, calculated by stereology and expressed in ml/m
WT: wild-type; Q247*: frame shift leading to stop codon instead of glutamine at amino acid 247; c.715_718dupTACG: a duplication of the indicated 4-nucleotide sequence, predicted to lead to a frameshift at the glycine at amino acid 240
List of abbreviations and definitions: CNS=central nervous system, CPK=Creatine Phosphokinase, CSVD=cerebral small-vessel disease, CT=computed tomography, LK=left kidney, RK=Right Kidney, NA= not available, US=ultrasound; T1DM, type 1 diabetes mellitus; T2DM, type 2 diabetes mellitus; pt, patient; TIA, transient ischemic attack; ID, infectious disease; MN, Membranous nephropathy;