Abstract

We describe the case of a 36-week gestational-age male stillborn with bilateral renal agenesis and a 47,XXY karyotype, as well as features of Potter sequence. No other congenital abnormalities were noted. Severe oligohydramnios was diagnosed prenatally at 30 weeks, and cytogenetic analysis was performed postmortem. Urinary tract anomalies are uncommon in association with Klinefelter syndrome. Unilateral renal agenesis has been described. We describe, to our knowledge, the first case of bilateral renal agenesis in association with 47,XXY.

Severe third-trimester oligohydramnios implies a higher risk for abnormal fetal karyotype, and it has been associated with fetal urinary tract anomalies in 8% to 33% of cases.1 

Up to 15% of congenital urogenital anomalies occur secondary to an underlying chromosomal disorder. The incidence ranges from 60% to 100% in certain chromosomal aberrations, including trisomy D and E as well as Turner syndrome.2,3 

Multiple congenital abnormalities have been associated with Klinefelter syndrome (47,XXY).4 However, gross malformations of the urinary tract are rare.2 

This article reports a case of bilateral renal agenesis in a fetus with 47,XXY. To our knowledge, this is the first such report.

REPORT OF A CASE

The propositus was a 36-week gestational-age stillborn, product of the second pregnancy of a 20-year-old healthy mother. The parents were nonconsanguineous. The pregnancy was complicated by severe oligohydramnios diagnosed at 30 weeks. Further testing, including magnetic resonance imaging at 31 weeks, showed bilateral absence of kidneys.

Postmortem examination showed a 1840-g stillborn male fetus with features of Potter sequence: compression deformity of the face, marked bilateral pulmonary hypoplasia, and talipes calcaneus varus. Bilateral renal agenesis was confirmed (Figure 1). The ureters were absent bilaterally. The bladder was tubular and hypoplastic. No other congenital anomalies were found.

Figure 1.

En bloc dissection, posterior view. Note bilateral absence of kidneys and downward placement of round adrenal glands (arrows). Figure 2. 47,XXY karyotype. Note presence of duplicated X chromosome (arrow)

Figure 1.

En bloc dissection, posterior view. Note bilateral absence of kidneys and downward placement of round adrenal glands (arrows). Figure 2. 47,XXY karyotype. Note presence of duplicated X chromosome (arrow)

A sample from the axillary skin was submitted for chromosomal analysis, which was performed by the high-resolution G-banding technique.

Examination of 3 metaphases revealed an abnormal male karyotype, 47,XXY, in all 3 (Figure 2).

COMMENT

Bilateral renal agenesis has been suggested to be multifactorial5–8 and has also been associated with the expression of a single dominant gene. Up to 10% of all newborns have significant abnormalities of the urinary system. The incidence of bilateral renal agenesis is 0.3 to 0.4 per 1000 newborns but reaches 3 per 1000 in stillborn fetuses.2 

Malformations of the urinary tract do not seem to occur more frequently in individuals affected with Klinefelter syndrome than in the normal population.2 Although uncommon, certain abnormalities of the urogenital tract have been described in association with the 47,XXY karyotype, including renal cysts,2 atresia of the pyelic cavity,9 atrophic scrotum, rudimentary penis,10 cryptorchidism, hypospadias, and unilateral renal agenesis and deformities.4 The case we describe appears to be the first case of 47,XXY with associated bilateral renal agenesis.

Fetuses with Klinefelter syndrome are not likely to be dysmorphic; therefore, cytogenetic analysis might not be performed at the time of postmortem examination in stillborn fetuses with seemingly isolated bilateral renal agenesis. For this reason, it is possible that previous cases of bilateral renal agenesis in fetuses with 47,XXY have been overlooked.

Acknowledgments

We thank Dale S. Huff, MD, Staff Pathologist at the Children's Hospital of Philadelphia and Associate Professor of Pathology, Hospital of the University of Pennsylvania, for his supporting comments and references.

References

References
Wax
,
J. R.
,
G.
Prabhakar
,
R. A.
Giraldez
,
G. M.
Hutchins
,
G.
Stetten
, and
K. J.
Blakemore
.
Unilateral renal hypoplasia and contralateral renal agenesis: a new association with 45, X/46, XY mosaicism.
Am J Perinatol
1994
.
11
:
184
186
.
Egli
,
F.
and
G.
Stalder
.
Malformations of kidney and urinary tract in common chromosomal aberrations, I: clinical studies [review].
Humangenetik
1973
.
18
:
1
15
.
Van Buggenhout
,
G. J.
,
J.
Verbruggen
, and
J. P.
Fryns
.
Renal agenesis and trisomy 22: case report and review.
Ann Genet
1995
.
38
:
44
48
.
Robinson
,
A.
,
H. A.
Lubs
,
J.
Nielsen
, and
K.
Sorensen
.
Summary of clinical findings: profiles of children with 47,XXY, 47,XXX and 47,XYY karyotypes.
Birth Defects Orig Artic Ser
1979
.
15
:
261
266
.
Buchta
,
R. M.
,
C.
Viseskul
,
E. F.
Gilbert
,
G. E.
Sarto
, and
J. M.
Opitz
.
Familial bilateral renal agenesis and hereditary renal adysplasia.
Z Kinderheilk
1973
.
115
:
111
129
.
Barakat
,
A. J.
Association of unilateral renal agenesis and genital anomalies.
Case Rep Clin Pract Rev
2002
.
3
:
57
60
.
Wilson
,
R. D.
and
P. A.
Baird
.
Renal agenesis in British Columbia.
Am J Med Genet
1985
.
21
:
153
169
.
McCallum
,
T. J.
,
J. M.
Milunsky
,
R.
Munarriz
,
R.
Carson
,
H.
Sadeghi-Nejad
, and
R. D.
Oates
.
Unilateral renal agenesis associated with congenital bilateral absence of vas deferens: phenotypic findings and genetic considerations.
Hum Reprod
2001
.
16
:
282
288
.
Tirnoveanu
,
G.
,
T.
Selaru
,
M. I.
Georgescu
,
V.
Frangulea
, and
G.
Mitescu
.
Sindrom Klinefelter asociat cu situs inversus total si malformatie renala.
Rev Med-Chir Soc Med Nat Iasi
1971
.
75
:
747
750
.
Srivastava
,
P. K.
,
B.
Brothinard
,
J. P.
Myers
, and
W. B.
Bradley
.
Klinefelter's syndrome in a boy with severe somatic and genital abnormalities: case report.
Mol Med
1977
.
74
:
597
598
.

The authors have no relevant financial interest in the products or companies described in this article.

Author notes

Corresponding author: Gary A. Stopyra, MD, Pathology Department, Pennsylvania Hospital, 800 Spruce St, Philadelphia, PA 19107 (stopyrag@pahosp.com)