Pediatr Nephrol (1996) 10: 498 – 500  IPNA 1996

Brief report Prevalence of renal malformation in Turner syndrome Myra T. Flynn1, Lori Ekstrom2, Miguel De Arce2, Colm Costigan3, and Hilary M. Hoey1 1

Department of Paediatrics, National Childrens Hospital, Trinity College, Dublin, Ireland Department of Genetics, Trinity College, Dublin, Ireland 3 Department of Paediatric Endocrinology, Our Lady’s Hospital, Dublin, Ireland 2

Received June 20, 1995; received in revised form and accepted November 30, 1995

Abstract. The presence of renal malformation was evaluated in 43 patients with Turner syndrome (TS) and compared with the karyotype in each case; 28 patients (65%) had a mosaic karyotype and the other 15 (35%) had only 45,X metaphases. Renal malformations characteristic of TS were found in 24% of the complete sample group. Of the 15 cases of pure 45,X karyotype, 8 (53%) had abnormal renal findings, while these were found in only 2 of the 28 mosaic cases (7.1%). The probability of this distribution having occurred by chance is P 0.05. More than 50% of girls with TS are said to have a renal anomaly. In this study renal malformations were found in 25% of the sample group. A significantly greater association of renal malformation was found with monosomy 45,X than with mosaicism. As mosaicism occurs in up to 60% of all girls with TS, the lower figure reported here represents a truer prevalence than that quoted in older series, where the figures quoted applied only to the 45,X syndrome.

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Key words: Turner syndrome – Renal malformation – Mosaicism

findings have been compared with the karyotype in each case. We report our results and document the association between individual karyotype and renal malformation. Patients and methods Patients. Forty-three girls with TS, who are attending two paediatric endocrine clinics in Dublin, were studied. The clinical diagnosis of TS was suspected initially on the basis of short stature, or delayed puberty, with a minority of patients being detected in infancy with classical dysmorphic features. The patients entered in this study were those for whom both karyotype and ultrasound examination of the kidneys were available, with no further selection. All were asymptomatic with regard to their renal tract. Cytogenetics. The clinical diagnosis of TS was confirmed in all girls by peripheral blood leucocyte karyotype between 1979 and 1994. For the exclusion of mosaicism, up to 50 metaphases were studied. If no other cell line was detected, the observation of 50 metaphases of karyotype 45,X ruled out the presence of a second cell line making up 6% of all cells with a probability of 95%. Mosaicism was established when at least three G-banded metaphases having a second karyotype were found. Further exclusion of a second cell line bearing additional X or Y chromosomes in 2% cells was possible in 5 of these girls, by scoring 100 interphase nuclei after X and Y dual-label colour fluorescence in situ hybridisation of cytogenetic slides using the Chromoprobe-I system from Cytocell (Oxfordshire, UK).

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Introduction Turner syndrome (TS) occurs at a frequency of 1 in 2,500 live female births. The classical karyotype is 45,X, but the 45,X cell line is seen in various forms of mosaicism [1]. Girls with TS display characteristic major and minor malformations, including structural renal anomalies [2 – 4]. We have studied the renal tracts of 43 girls with TS as part of routine screening, using ultrasonography. The prevalence of renal malformations has been estimated and the renal

Correspondence to: M. Flynn, Department of Genetics, Trinity College, Dublin 2, Ireland

Ultrasound. Renal ultrasonography was performed in the 43 girls with an ATL Ultramark-4 real time scanner using 3.0-MHz and 5.0-MHz frequency probes.

Results Ultrasound Renal abnormalities were observed in 10 of the 43 girls (24%), while the other 33 (76%) gave normal results (Table 1). The renal malformations seen were typical of those described previously in TS [2 – 4]. Six patients were found to have a horseshoe kidney, 2 had right-sided duplex renal collecting system, 1 had right-sided renal agenesis and 1 had a simple renal cyst.

499 Table 1. Cytogenetics and renal malformation in 43 Turner syndrome (TS) girls Patient no.

Karyotype

No. cells Renal abnormality karyotyped

1– 7 8 – 12 13 – 14 15

45,X 45,X 45,X 45,X

50 50 50 50

None Horseshoe kidney Duplex collecting system Absent kidney

Ratio renal anomaly: in pure 45X TS patients = 8/15 16 17 18 19 20 21 22 23 24 25

45,X/46,XX 45,X/46,XX 45,X/46,XX 45,X/46,XX 45,X/46,XX 45,X/46,XX 45,X/46,XX 45,X/46,XX 45,X/46,XX 45,X/46,XX

7/18 23/4 22/3 34/6 13/7 10/3 18/3 18/2 36/4 19/3

None None None None None None None None None Renal cyst

26 27 28 29 30 31 32

45,X/46,XiXq 45,X/46,XiXq 45,X/46,XiXq 45,X/46,XiXq 45,X/46,XiXq 45,X/46,XiXq 45,X/46,XiXq

6/4 5/21 6/4 7/3 3/9 11/21 19/12

None None None None None None Horseshoe kidney

33 34 35 36 37 38 39

45,X/46,XrX 45,X/46,XrX 45,X/46,XrX 45,X/46,XrX 45,X/46,XrX 45,X/46,XrX 45,X/46,XrX

8/3 27/3 27/3 8/3 7/3 14/46 24/10

None None None None None None None

40 41

45,X/47,XXX 45,X/47,XXX

18/61 15/3

None None

42

45,X/46,XY

Not recorded

None

43

45,X/46,XdelXp11

4/61

None

Ratio renal anomaly: in mosaic TS patients = 2/26 Overall ratio renal anomaly: in all TS patients = 10/43

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Cytogenetics The karyotype 45,X was observed in 15 of the 43 girls (35%), of whom 8 (53%) had a renal abnormality (Table 1). Mosaic karyotypes were observed in 28 girls (65%) and one had a non-mosaic structural aberration of the X chromosome. In this group, only 2 of 28 (7%) had a renal abnormality. Table 1 also records the proportion of both cell lines in mosaics. Discussion The prevalence of renal malformation in TS has been quoted as being greater than 50% in older series. The topic has not received much recent attention in the literature. One 1988 review [4] gives a prevalence of 33%, significantly lower than all previous reports. Major texts continue to list

renal malformation in TS as occurring in about 33% – 60% of all cases of TS [5, 6]. In this study renal malformation was found in 24% of cases. The most striking finding was the high association between renal abnormality and pure monosomy 45,X, with 8 of 15 monosomic patients affected. In contrast, renal anomaly was not shown to be a typical feature of mosaic TS, with only 2 of 28 such patients having an abnormal ultrasound. Assuming an equal risk of renal abnormality for mosaics and non-mosaics, estimated as an overall risk of 0.24 (10/43), the probability of such a distribution is low (P = 0.017). Of the girls studied, 60% had mosaic karyotypes, a finding similar to other recent TS series [7]. The lack of association between mosaicism and renal malformation and the predominance of mosaicism in the sample group serves to explain the lower prevalence shown here. Mosaic TS girls do not express the full TS phenotype and therefore may escape detection, only coming to medical attention in the 2nd decade as a chance finding on investigation of short stature or primary amenorrhoea. Given mosaic TS patients underexpress the other manifestations of TS, one would expect that there would be fewer renal malformations in this group. However, although the prevalence of renal malformation is less, both structural and positional abnormalities do occur in mosaics. Current recommendations are that all forms of TS should have routine nephrological screening on diagnosis [5]. The majority of mosaics in our sample group contain 50% cells of karyotype 45,X, including the 2 cases with renal anomaly. The severity of some of the features of the TS phenotype have been found to be associated with the proportion of 45,X metaphases in blood cells [8], and this could also determine the likelihood of renal anomalies. Our sample, however, does not contain enough patients of the same level of mosaicism to draw conclusions in this regard. As mosaicism is increasingly recognised in TS, the lower prevalence of renal anomaly reported here will be found to represent a truer estimation of the problem. We propose that the higher rates of renal abnormality quoted in previous series were those seen with monosomy 45,X alone. We conclude that renal malformation occurs in approximately 24% of all girls with TS, and that it is seldom seen in girls with mosaic karyotype, who form the predominant subgroup.

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Acknowledgements. This work was funded by a research grant from Serono Pharmaceutical UK.

References 1. Hook EB, Warburton D (1983) The distribution of chromosomal genotypes associated with Turner syndrome: livebirth prevalence and evidence for diminished fetal mortality and severity in genomes associated with structural X abnormalities or mosaicism. Hum Genet 64: 24 – 27 2. Matthies A, Macdiarmaid WD, Rallison ML (1971) Renal anomalies in Turner’s syndrome. Clin Pediatr (Phila) 10: 561 – 565 3. Persky L, Owens R (1971) Genitourinary tract abnormalities in Turner syndrome. J Urol 105: 309 – 313

500 4. Lippe B, Geffner ME, Dietrich RG, Boechat MI, Kangarloo H (1988) Renal malformations in patients with Turner syndrome: imaging in 141 patients. Pediatrics 82: 852 – 856 5. Hall JG (1992) Turner syndrome. In: King RA, Rotter JI, Motulsky AG (eds) The genetic basis of common diseases. Oxford University Press, New York and Oxford, p 895 6. Patton MA (1992) Genetics. In: Campbell AGM, McIntosh N (eds) Forfar and Arneil’s textbook of paediatrics Churchill and Livingstone Edinburgh and New York, pp 67 – 68

7. Held KR, Kerber S, Kaminsky E, Singh S, Goetz P, Seemanova E, Goedde HW (1992) Mosaicism in 45X Turner syndrome: does survival in early pregnancy depend on the presence of two sex chromosomes? Hum Genet 88: 288 – 294 8. Sarkar R, Marimuthu KM (1983) Association between the degree of mosaicism and the severity of syndrome in Turner mosaics and Klinefelter mosaics. Clin Genet 24: 420 – 428

Literature abstracts Indian Pediatrics (1995) 32: 1281 – 1286

Behavior problems in nephrotic syndrome Manju Mehta, Arvind Bagga, Pratibha Pande, Geeta Bajaj, and R. N. Srivastava Objectives. To evaluate the adaptive competences and behavioral problems in children with nephrotic syndrome, and whether their mothers also showed features of psychosocial stress. Design. Prospective case-control study. Setting. Pediatric Out-Patient Department. Subjects. Seventy consecutive patients of nephrotic syndrome, between the ages of 4 to 14 years, and their mothers constituted cases. The control group, matched for age, sex and socioeconomic status comprised of 46 children and their mothers. The mother’s description of the child’s behavior, on the Child Behavior Checklist (CBCL), was obtained to assess behavioral problems and social competences. The level of anxiety in the mother was assessed using the PGI Health Questionnaire N2.

Results. Children with nephrotic syndrome showed features of depressed, hyperactive or aggressive behavior. Somatic complaints, social withdrawal and poor school performance were also observed. These problems did not interfere with compliance to treatment and only 7 patients required psychological interventions. Boys with nephrotic syndrome had more hyperactive and aggressive behavior as compared to girls. The scores on the CBCL were well correlated with the anxiety scores of the mother. Conclusions. These observations suggest the presence of minor behavior problems in a significant proportion of children with nephrotic syndrome. The severity of these problems may be related to the attitude of the mother towards the child’s illness.

Nephrol Dial Transplant (1995) 10: 2224 – 2227

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Changing pattern of primary hyperoxaluria in Switzerland N. Kopp and E. Leumann Background. The clinical course of primary hyperoxaluria (PH) is greatly variable and diagnosis is often delayed. Little is known about the overall occurrence and current prognosis. Methods. We evaluated all known patients with PH residing and observed in Switzerland during the last 15 years with the help of a survey among Swiss nephrologists. Results. Of the 25 patients observed between 7/79 and 6/94 in Switzerland. 18 were alive in 1994 – 14 on conservative therapy and four on renal replacement therapy (RRT). Twenty-two patients had PH type 1; the exact type was not determined in three. The estimated preva-

lence of PH (type 1) is 2 per million population; the minimal incidence is 1 per 100 000 live births. Diagnosis was delayed by 8 years (median) except in infants. Five patients were pyridoxine sensitive. According to life table analysis, 20% of patients were in end-stage renal failure (ESRF) and 10% had died by the age of 15 years, and 50% were in ESRF and 20% dead at 25 years. Prognosis has improved: Five of 13 patients died during the first half of the observation period as opposed to two of 20 in the second part. Conclusions. Overall prognosis appears better than hitherto believed considering the large clinical spectrum of PH. Greater awareness of PH is needed to improve further long-term prognosis.