PEDIATRICS Vol. 118 No. 6 December 2006, pp. e1900-e1903 (doi:10.1542/peds.2006-0955)
EXPERIENCE & REASON |
Monozygotic Twins With Turner Syndrome Develop Slipped Capital Femoral Epiphysis on Growth Hormone Therapy
Section of Pediatric Endocrinology, Department of Pediatrics, James Whitcomb Riley Hospital for Children, Indiana University School of Medicine, Indianapolis, Indiana
ABSTRACT
Monozygotic twins with Turner syndrome have rarely been reported. An increased incidence of slipped capital femoral epiphysis has been associated with growth hormone therapy, as well as with Turner syndrome, but has never been described in twins with Turner syndrome. We report the first case of monozygotic twins with Turner syndrome with a 46,Xi(Xq) karyotype, both of whom developed slipped capital femoral epiphysis during growth hormone therapy. This report adds to existing reports of monozygotic twins with Turner syndrome and contributes to recognition of the potential clinical course in such patients. In addition, the association between slipped capital femoral epiphysis, growth hormone therapy, and Turner syndrome is emphasized.
Key Words: Turner syndrome • growth hormone therapy • slipped capital femoral epiphysis
Abbreviations: TS, Turner syndrome • SCFE, slipped capital femoral epiphysis • GH, growth hormone
Turner syndrome (TS) is a disorder in females characterized by complete or partial absence of an X chromosome in association with typical phenotypic features.1 TS occurs in 1 in 2500 live-born girls, with 50% having monosomy X (45,X).2 The first case of twins with TS was reported by Turner in 1938.1 The twins were presumably fraternal, with one twin showing all features of the syndrome and the other twin appearing normal. Since this original report, the association between TS and twinning has been noted in >30 cases. However, there are only 6 reports in the literature of monozygotic nonmosaic twins with TS, all of whom were 45,X.3–8 Although slipped capital femoral epiphysis (SCFE) has rarely been described in identical twins9–12 and is known to occur in patients on growth hormone (GH) therapy, it has never been reported in twins with TS. Thus, this is the first report of 46,X,i(Xq) monozygotic twins with identical manifestations of TS who developed SCFE during GH therapy.
CASE REPORTS
Twin A was a 13 2/12-year-old white girl who was referred for evaluation of short stature. She was born by cesarean section because of breech presentation and twin gestation at 34 weeks. Monozygosity was established by the finding of a monochorionic diamniotic pregnancy at 12 weeks' gestation. The pregnancy was uncomplicated, and the patient's past medical history was significant only for recurrent ear infections.
At the initial visit, her height was 134.6 cm (<5th percentile; –3.38 SDs), weight was 54.4 kg (75th percentile), and BMI was 30 kg/m2 (>95th percentile). On physical examination, she had several typical TS stigmata including a high arched palate, low posterior hairline, and posteriorly rotated ears in addition to Tanner II breasts and Tanner II pubic hair. Her karyotype was 46,X,i(Xq). Gonadotropin levels, renal ultrasound, echocardiography, and thyroid-function tests were normal.
One month later, twin B was referred for similar concerns. Her height was 135.8 cm (<5th percentile; –3.28 SDs), weight was 53.9 kg (75th percentile), and BMI was 29.2 kg/m2 (>95th percentile). She had identical phenotypic features with Tanner III breasts and Tanner I pubic hair. Her karyotype was also 46,X,i(Xq) and results of additional evaluation were normal with the exception of a mild bicuspid aortic valve. After the diagnosis of TS, both patients were started on GH therapy at 0.375 mg/kg per week. Figure 1 shows the phenotypic features of the twins at 16 years of age.
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Development of Ovarian Failure
One year after the diagnosis of TS, both girls were noted to have lack of progression of normal puberty. Repeat testing of gonadotropin levels revealed gonadal failure with luteinizing hormone and follicle-stimulating hormone levels of 19.0 and 53 mIU/mL (twin A) and 19.5 and 74.9 mIU/mL (twin B), respectively. Hormone-replacement therapy with estrogen was started at 14 2/12 years of age, and progesterone was added 2 years later.
Development of SCFE on GH
Sixteen months after the start of GH therapy, twin A developed severe right hip pain. Radiographs of the hip and pelvis confirmed unilateral right SCFE. Growth velocity at this time was 5.5 cm/year. Pinning of both hips was performed (Fig 2). Three weeks later, twin B presented with a 1-week history of right hip pain. The diagnosis of SCFE was made, and she also underwent bilateral pinning of the hips. Her growth velocity at the time was 6.9 cm/year. Although GH was temporarily held, it was restarted 2 months after the hip surgery. After a total of 3.5 years of GH therapy, twins A and B achieved final heights of 152.4 cm (5th percentile; –1.69 SDs) and 151.9 cm (5th percentile; –1.61 SDs), respectively. Initial and subsequent laboratory studies as well as clinical course in these patients are summarized in Table 1.
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DISCUSSION
Twinning usually occurs once in 85 pregnancies, and only 25% of twins are monozygotic.8 However, the incidence of twinning in families of individuals with TS has been reported to be higher than in the general population.13 Of 30 reports of twinning involving TS, there are only 6 cases of monozygotic nonmosaic twins, all with a 45,X karyotype as shown in Table 2. Thus, our patients represent the first case of monozygotic nonmosaic TS twins with an (X,iXq) chromosomal complement.
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Of girls with TS, 10% to 15% have a duplication of the long arm of 1 X chromosome, which is termed an isochromosome Xq.2 Unlike in patients with monosomy X, in whom the incidence of spontaneous puberty is only 9%, girls with TS with structural X chromosome abnormalities may have up to a 28% incidence of spontaneous puberty.14 However, as was the case for our patients, subsequent ovarian failure in these girls is common.2
The incidence of SCFE in the general population is 0.7 to 3.4 per 100000.15 Although SCFE is known to occur with increased frequency in patients on GH therapy,16 it is also more common in girls with TS regardless of GH treatment.17 SCFE in otherwise normal identical twins has been described in 4 cases,9–12 of whom 2 were female. Risk factors for SCFE include increased BMI and peripubertal or pubertal age.18 A possible genetic predisposition has been suggested by similarities in HLA phenotype.10,11 In fact, SCFE has been suggested to be an autosomal dominant trait with variable penetrance.19 Therefore, there are multiple potentially contributing factors for the development of SCFE in girls with TS. These include a propensity for obesity, GH treatment, hypogonadism,20 and perhaps an intrinsic predisposition caused by an abnormal complement of X-chromosome genes.
CONCLUSIONS
This case illustrates a unique constellation of features in association with a karyotype that has not been previously reported in a monozygotic nonmosaic TS twinship. Associations between TS, SCFE, GH treatment, and development of ovarian failure in girls with an isochromosome X are important considerations in the health maintenance of patients with TS.
FOOTNOTES
Accepted Jun 19, 2006.
Address correspondence to Zeina M Nabhan, MD, Pediatric Endocrinology/Diabetology, Riley Hospital for Children, Room 5960, 702 Barnhill Dr, Indianapolis, IN 46202. E-mail: znabhan{at}iupui.edu
The authors have indicated they have no financial relationships relevant to this article to disclose.
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PEDIATRICS (ISSN 1098-4275). ©2006 by the American Academy of Pediatrics
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