Hum Genet (1992) 89:666-670

9 Springer-Verlag 1992

Crossed renal ectopia with pelvic lipomatosis: a new syndrome involving chromosome 1 H.K. Goswami 1, G.V. Rangnekar 2, S. Varshney 2, Puneet Gandhi 1, Babita Jain t, and A. Joshi 2 1Department of Genetics, The University Campus, Bhopal 462026, India 2Department of Surgery, Gandhi Medical College, Bhopal, India Received June 15, 1991 / Revised November 20, 1991

Summary. An 18-year-old male patient is described who possesses both kidneys on one side (crossed renal ectopia), together with pelvic lipomatosis. In general, lipomatosis is benign, but here the tissue shows the rare feature of malignancy. Chromosomally, the patient is typically characterised by somatic translocations involving c h r o m o s o m e 1 (37% metaphases); these almost always exhibit a whole c h r o m o s o m e translocation with chromosome 6 (35%), although involvement of chromosome 1 with c h r o m o s o m e 8 is present in 2% of metaphases. Other chromosomal features encountered in Giemsastained and G - b a n d e d preparations from lymphocyte cultures include the prevalence of a small Y chromosome in 25% of metaphases, the presence of m a r k e r dots in 20%, and acrocentric associations in 8 % - 1 0 % of metaphases. However, more than 50% of metaphases have a normal 46XY karyotype with a normal-sized Y-chromosome. Crossed renal ectopia with pelvic lipomatosis can therefore be assigned to a new syndrome characterised by a whole-chromosome translocation involving chromosomes 1 and 6.

Materials and methods An 18-year-old male patient was admitted to the Surgical Ward of Hamidia Hospital and Gandhi Medical College with a severely swollen abdomen. The patient had suprapubic and perineal swellings (Figs. 1,2). He was subjected to routine pathological and biochemical examination. Pertinent investigations by intravenous urogram, barium enema and ultrasonography were immediately performed. The patient was surgically examined in order to find any internal anatomical manifestations, displacements or growths; this procedure revealed that the patient had both his kidneys on the right

Introduction The combined occurrence of crossed renal ectopia and pelvic lipomatosis in one patient is unknown, although both conditions have been independently reported (see Campbell 1985) for some time. Pelvic lipomatosis is a localised form of obesity resulting in proliferation of pelvic adipose tissue and compression of various pelvic viscera, including the ureter and bladder. Fewer than 100 cases are known in the literature. Similarly, crossed renal ectopia (the presence of both kidneys on one side of the mid-line) is a rare condition (Perlumutter et al. 1985). Therefore, this patient is of unusual significance. The patient also possesses a whole-chromosome translocation involving chromosomes 1 and 6, in addition to many other chromosomal abnormalities. Correspondence to: H. K. Goswami or G.V. Rangnekar

Fig. 1. Patient showing lean build with suprapubic lump (revealed on exploration) Fig. 2. Patient lying down to show perineal swelling

667 side. CT (computed tomography) scan pictures and a small biopsy from the suspected kidney confirmed our diagnosis. Chromosome studies were made on two occasions (with a gap of 1 month after the surgical operation) by the usual lymphocyte cultures in TC 199 and RPMI (Goswami 1986a, b, 1990) media. Cells were harvested after 69 h and processed for Giemsa staining. One-week-old slides were routinely G-banded. The chromosomal profile of the patient was based on 40 G-banded and more than 60 Giemsa-stained metaphases.

Haematological/biochemical findings Investigations revealed: Hb 7.8 g%, total and differential white blood cells 11.900/cmm, P 70%, L 23%, E 7%, S. creatinine 0.4 mg%, acid phosphatase 1.5 KA, alkaline phosphatase 4 KA. Urine showed the presence of albumin; E. coli showed a 103 colony count in culture.

Diagnostic investigations Results

Physical findings The propositus is an 18-year-old male with suprapubic (Fig. 1) and perineal swellings (Fig. 2), and complaining of dribbling of urine, pain in the abdomen and loss of appetite and weight for more than 6 months. He is of lean build (BP 140/100) with no organomegaly, ascites or pedal oedema. The suprapubic swelling (14 x 10 cm) is firm but tender, immobile and non-pulsatile. The swelling in the perineum (8 cm in diameter) is immobile and lies between the scrotum and anal opening. Anorectal examination revealed reduced sphincter tone; piles were also seen. Clubbing and gynaecomastia were present.

Ultrasonography. The crossed renal ectopia exhibited a hyperechoeic area of homogeneous architecture in the suprapubic region. An intravenous urogram (Fig. 3) shows both kidneys on the right side with hydro-ureteronephrosis of the right kidney. A C T scan shows crossed renal ectopia with fusion (Fig. 4). The left kidney is present in t h e right pelvis. Exploratory laprotomy did not reveal the left kidney in its normal place; however, a biopsy from the tissue mass in the right iliac fossa showed glomeruli and normal kidney tissue. Pelvic lipomatosis. Exploratory laprotomy identified a diffuse yellowish mass infiltrating into the pelvic retroperitoneum. CT scan (Fig. 5) shows increased adipose

Fig. 3. Intravenous urogram showing crossed renal ectopia on right side with hydroureteronephrosis of right kidney Fig. 4. CT scan showing crossed renal ectopia Fig. 5. CT scan showing pelvic lipomatosis Fig. 6. Barium enema showing displacement and straightening of rectosigrnoid Fig. 7. Cystogram showing distortion of bladder and displacement to the left side

668

Fig. 8. A lymphocyte (treated with NaC1 instead of KC1 for hypotonic treatment) shows 2n = 46XY chromosomes. Note the wholechromosome translocation involving chromosomes 1 and 6 (arrow). • 2250 Fig. 9. A major part of the Gbanded metaphase plate, showing the whole-chromosome translocation and small Y chromosome. x 2500 Fig. 10. A metaphase spread showing the marker dot chromosome (arrow)

Table 1. Major types of chromosomal aberration a encountered among 284 individuals (including data from Goswami et al. 1990). PCD, Premature centromeric division Earlier and No. of

No. persons exhibiting abnormalities (frequency)

and present study

persons examined b

Translocations

ControlA: randomly selected seemingly normal individuals

Earlier Present

74 (58) 27 (20)

2 (0.02) 2 (0.07)

-

9 (0.12) 5 (0.18)

3 (0.04) 2 (0.07)

2 (0.02) 3 (0.11)

Control B: parents/sibs of affected persons c

Earlier Present

27 (17) 23 (13)

2 (0.07) 3 (0.13)

1 (0.03) 2 (0.08)

3 (0.11) 9 (0.39)

1 (0.03) 4 (0.17)

4 (0.14) 5 (0.21)

3 (0.11) 2(0.08)

2(0.07) 4(0.39)

Persons exposed to gas (MIC) in Bhopal

Earlier Present

53 (08) 04 (02)

42 (0.79) 1 (0.25)

8 (0.15) -

24 (0.45) 2 (0.50)

16 (0.30) 2 (0.50)

12 (0.22) 1 (0.25)

29 (0.54) -

5 (0.09) 1 (0.25)

34 (14)

3 (0.08)

2 (0.05)

7 (0.28)

10 (0.29)

17 (0.50)

14 (09) 14 (02)

2 (0.14) 4 (0.28)

-

2 (0.14) 10 (0.71)

1 (0.07) 3 (0.21)

4 (0.28) 7 (0.49)

14 (07)

5 (0.35)

2 (0.14)

2 (0.14)

3 (0.21)

3 (0.21)

Non-specific mentally under-developed individuals (both sexes) Recurrently aborting couples Other syndromes

Husband Wife

Ring chromosomes

Marker dot

Deletions/ Mosaic chromocells some breaks/ accentric fragments

Inversions

PCD

n

3(0.11)

-

1 (0.029) 2 (0.05)

4 (0.28) 8 (0.56)

-

2(0.14)

3 (0.21)

a Chromosome 1 was never involved b Number of chromosomally normal persons are shown in parenthesis c Persons who are under specific treatment and have been chromosomally examined

tissue in the pelvic r e g i o n a n d s i g m o i d m e s o c o l o n . A b a r i u m e n e m a clearly r e v e a l e d t h e d i s p l a c e m e n t of the s t r a i g h t e n e d r e c t o s i g m o i d to the right ( a n t e r i o r ) side (Fig. 6). A c y s t o g r a m of t h e p a t i e n t s h o w e d a d i s t o r t e d b l a d d e r d i s p l a c e d to the left (Fig. 7).

C y s t o s c o p y was p e r f o r m e d u n d e r g e n e r a l a n a e s t h e s i a ; this also c o n f i r m e d the left side d i s p l a c e m e n t of the b l a d der. T h e p r o s t a t i c p o r t i o n o f t h e u r e t h r a was slightly def o r m e d . A b i o p s y f r o m the p e r i n e a l swelling e x h i b i t e d m a t u r e a d u l t fat cells c o n s i s t e n t with l i p o m a t o s i s . H o w -

669 Table 2. Chromosomal profile of a patient with crossed renal ectopia with pelvic lipomatosis (based on 100 metaphases) Description

Remarks

Male 46 XY Whole chromosome translocation involving chromosomes i and 6 chromosomes i and 8 Acrocentric association Small Y chromosome Presence of marker dot

Figs. 1, 11A 35% metaphases (Fig. 11B) 2% metaphases 10% metaphases (Fig. 8) 25% metaphases (Figs. 9, 11) 20% metaphases (Fig. 10)

ever, surprisingly, the patient exhibits a malignant form of lipomatosis on account of following features: loss of weight, loss of appetite, sacral erosion and an increment in the size of the swelling.

Chromosomal features Well-spread Giemsa-stained and G-banded metaphases (n = 120) have been examined, the chromosomal profile of the propositus being as follows. (1) The patient has a normal male karyotype (2n = 46XY). (2) Nearly 35% of metaphases reveal chromosomes 1 and 6 exhibiting a whole translocation (Fig. 8). This feature is typical of this patient and is observed both in Giemsa-stained and in G-banded metaphases (Fig. 9). (3) Some 20% of metaphases always reveal a small Y chromosome (Fig. 9) and a marker dot (Fig. 10). (4) Some 8%-10% metaphases possess Robertsonian translocations involving large and small acrocentric chromosomes (Fig. 8). Apart from these significant aberrations, we have also observed hypoploid (42-43 chromosomes; 2%) and hyperploid (47-48 chromosomes; 2%) metaphases. In order to compare the above observations with matched controls (randomly selected) and with patients affected by known pathological conditions and their family members, data on 284 individuals are presented in Table 1, which also indicates comparable gross features. Table 2 gives those features that may be considered typical of

chromosomal involvement in crossed renal ectopia with pelvic lipomatosis.

Discussion

Clinical picture Following the description of crossed renal ectopia in 1654 by Pamarlous, about 100 cases have been described, the majority of which have been in male subjects. This anomaly of crossed over ectopia is said to be the result of misalignment and abnormal rotation of the caudal end of the developing fetus, with the distal end of the vertebral column being displaced to one side (Gray and Skandalakis 1972). Among the causes of renal ectopia, which include ureteral bud malformation and defective metanephric tissue that fails to induce ascent, there is a record of genetic influence, based on many individuals of one family exhibiting the anomaly (Greenberg and Nelsen 1971; Hildreth and Cass 1978). The mother and a sister of the propositus reported here were investigated and found to possess no such abnormality. Male members of his family have not as yet been examined. The patient has an extremely rare combination, which has never been reported previously, of crossed renal ectopia with a pelvic lipomatosis, a benign tumour essentially involving mature fat in the pelvic retroperitoneal space. The proliferative adipose tissue has compressed the pelvic viscera, including the pelvic portion of the ureters. Fewer than 100 cases of pelvic lipomatosis are known in literature (Persky et al. 1985), and in only 4 of these has the tumour been in female subjects. Characteristically, the present patient has a unique chromosomal aberration hitherto unknown for such an anomaly.

Chromosomal involvements Greenberg and Nelsen (1971) and Hildreth and Cass (1978) have described a family in which many individuals suffer from renal ectopia. However, this paper is the first

Fig. 11. A G-banded karyotype 46XY. B (inset) shows the wholechromosome 1 and 6 translocation: the other chromosome 6 also lies in vicinity (see also Fig. 9)

670 report on chromosomal involvements in a patient of crossed renal ectopia with pelvic lipomatosis. We have, so far, been unable to investigate his parents, but the propositus himself has been investigated twice to provide consistent observations of the associated abnormalities.The first and foremost observation is the regular involvement of the whole-chromosome translocation of chromosome 1, mostly on c h r o m o s o m e 6 (Fig. l l b ) . Nearly 50% of metaphases have the normal 46XY karyotype. The involvement of chromosome 1 in the translocation (with chromosome 6) may be typical of this rare association of crossed renal ectopia with lipomatosis. C h r o m o s o m e 1 has never previously been found to be involved in any of the 284 individuals whom we have studied during the past 5 years (including data from Goswami et al. 1990; see Table 1). Goswami et al. {1990) have observed that c h r o m o s o m e 1 did not respond to Bhopal methyl isocyanate (MIC) exposure, although other constitutive heterochromatin-rich chromosomes (9 and 16) did show aberrations. Table 1 also shows unpublished data on observations on mentally underdeveloped individuals, recurrently aborting w o m e n and their husbands, and some other syndromes, together with their relatives and randomly studied controls. The detailed features of these individuals will be published at a later date, but our principal motive in presenting these data is to stress that whole-chromosome translocation of chromosomes 1 and 6 seen in our patient may be an important feature of this syndrome, Other aberrations, such as acrocentric associations and the presence of marker dots, cannot be exclusively associated with this rare anomaly (see Table 1). The presence of m a r k e r dots has mostly been found to be indicative of malignant involvement (see Goswami et al. 1990); the present observations appear to conform to this hypothesis. Pelvic lipomatosis is, by nature, a benign condition, but surgical and histopathological observations have revealed neoplastic changes in the biopsy of the tissue from our patient. However, marker dots have also been observed in otherwise normal individuals and therefore need no special emphasis at the moment.

Involvement of chromosome 1 There are few reports of aberrant involvements of chrom o s o m e 1. Borgaonkar (1991) has listed only l p partial m o n o s o m y syndrome, lq partial m o n o s o m y (q21-q32) syndrome, lq partial m o n o s o m y (q42-qter) syndrome and lq partial trisomy syndrome. However, none of the above reports involves whole-chromosome translocation of chromosome 1 to chromosome 6 and vice versa. There are two possibilities: either chromosomes 1 and 6 have joined end to end (telomere association; see T h e r m a n 1980), or they have interchanged their telomeres. Since unbroken c h r o m o s o m e ends do not, as a rule, join to

each other and are capped by telomeres, the second possibility (Figs. 8, 9) seems more probable. As an exception (see T h e r m a n 1980), however, direct joining of chromosomes is known in human chromosomes. Hayashi and Schmid (1975) have indicated a similar possibility in ataxia telangiectasia. Nevertheless, we believe, particularly when such a translocation is reccurrently found in the patient, that telomere interchange is probably more frequent than telomere fusion (see also Pearson et al. 1977). In our opinion, all the above clinical and chromosomal characteristics support the hypothesis that crossed renal ectopia with pelvic lipomatosis involving a chromosome 1 whole translocation should be regarded as a new syndrome.

AcknoWledgements. We are grateful to the patient and his family for their full co-operation. Thanks are due to Professor D. S. Borgaonkar for his great help. Suggestions received from Dr.L.K. Sengupta and Dr. (Mrs.) Sengupta are also gratefully acknowledged.

References Borgaonkar DS (1991) Chromosomal variation in man. A catalog of chromosomal variants and anomalies, 6th edn. Liss, New York Campbell MF (1985) Anomalies of the kidney. In: Campbell MF, Harrison JH (eds) Urology, vol 2, 4th edn. Saunders, Philadelphia Goswami HK (1986a) Practical cytology, applied genetics and biostatistics. Himalaya Publishing House, Bombay Goswami HK (1986b) Cytogenetic effects of methyl isocyanate exposure in Bhopal. Hum Genet 74 : 81-84 Goswami HK, Chandorkar M, Bhattacharya K, Vaidyanath G, Parmar D, Sengupta S, Patidar SL, Sengupta LK, Goswami R, Sharma PN (1990) Search for chromosomal variations among gas-exposed persons in Bhopal. Hum Genet 84:172-176 Gray SW, Skandalakis JE (1972) Embryology for surgeons. Saunders, Philadelphia Greenberg LW, Nelsen CE (1971) Crossed fused ectopia of kidneys in twins. Am J Dis Child 122 : 175 Hildreth TH, Cass AS (1978) Cross renal ectopia with familial occurrence. Urology 12 : 59 Hayashi K, Schmid W (1975) Tandem duplication q14 and dicentric formation by end-to-end chromosome fusions in ataxia telangiectasia (AT). Clinical and cytogenetic findings in 5 patients. Humangenetic 30:135-14 l Pearson P, Graver J, Estop A, Dijksman T, Wojnen L, Meerakhan PM (1977) The chromosomes of non-human primates, in: Sparker RS, Comings DE, Fox CF (eds) Molecular human cytogenetics. Academic Press, New York, pp415-425 Perlmutter AD, Retik AB, Bauer SB (1985) Anomalies of the upper urinary tract. In: Campbell MF, Harrison JH (eds) Urology, vo12. Saunders, Philadelphia, pp 1665-1759 Persky L, Kursh ED, Feldman S, Resnick MI (1985) Extrinsic obstruction of the ureter. In: Campbell MF, Harrison JH (eds) Urology, vol 2. Saunders, Philadelphia, pp 579-615 Therman E (1980) Human chromosomes: structure, behaviour, effects. Springer, Berlin Heidelberg New York