Turner syndrome (TS) is a congenital disorder with a combination of characteristic phenotypic features caused by loss of the entire X chromosome or a critical part of it. The genetic background of the TS phenotype is highly variable; in addition, mosaicism with two or more cell lines may be present. The classical karyotype 45,X accounts for more than 50% of cases. The remaining cases may have mosaic karyotypes (i.e., cells with 45,X and cells with 46,XX) or structural abnormalities of chromosome X or Y [Kavoussi et al., 2006]. The structural anomalies of the X chromosome comprise isochromosomes of the long arm, dicentric chromosomes and deletion of the short arm or ring chromosomes. Abnormalities of the Y chromosome include isochromosomes of the long arm and dicentric chromosomes [Verver et al., 2011]. Turner syndrome is the most common sex chromosome abnormality in females. Estimates suggest that the number of females born with TS ranges from 1:2,000 to 250 live born girls [Kappelgaard and Laursen, 2011].
The most common features of TS are pre- and post-natal growth retardation and gonadal dysgenesis [Kavoussi et al., 2006]. The craniofacial features include triangular face, epicanthic folds, short nose with elevated base and tip, small receding chin, low-set and malformed ears, high palate, webbing of the neck and low hairline [Dumancic et al., 2010]. Short stature is a hallmark of Turner syndrome and occurs in almost 100% of cases. Short stature often includes a disproportionate increase in weight, thereby placing these girls at increased risk for health issues associated with overweight [Elleuch et al., 2010]. Much of the deficit in height is caused by haploinsufficiency of the short-stature homeobox-containing gene (SHOX) located within the pseudoautosomal region of the X chromosome. Skeletal abnormalities are not restricted to linear growth. Disproportionate growth causes most girls with TS to appear stocky, with a wide body and relatively large hands and feet. The localization to the elbow, knee, and wrist during embryonic development is consistent with the increased prevalence of cubitus valgus, genu valgum, and short fourth metacarpals in girls with TS [Davenport and Keizer-Schrama, 2006]. At birth, identification of edematous hands and feet may raise the suspicion of TS, which can be confirmed by chromosomal analysis. Webbed neck, ear deformities, broad chest, and cardiac or renal malformations may also be apparent [Keizer-Schrama, 2007]. Girls with TS are typically born with mild intrauterine growth retardation. They usually grow slowly during infancy and childhood and fail to undergo a pubertal growth spurt [Morgan, 2007; Hsu et al., 2008]. Because bone maturation is generally delayed, most untreated girls with TS grow slowly into their early 20s, achieving an adult height about 20 cm shorter than their target height [Davenport and Keizer-Schrama, 2006]. Since heights of girls with TS should be plotted on TS growth curves specific to ethnic groups and/or nationalities, our work aims to evaluate the pattern of growth curves in Egyptian females with Turner syndrome.
MATERIALS AND METHODS
This study included 93 patients diagnosed by cytogenetic analysis as classic or mosaic TS, having 45,X or 45,X/46,XX karyotype. All patients were recruited from the Clinical Genetics Department, National Research Centre in Egypt. Chronological age ranged from 6 months to 24 years (mean 10 ± 4.3 years). None of the patients was treated with human recombinant growth hormone. Complete clinical evaluation was done for all patients with special emphasis on dysmorphism. Cytogenetic analysis was performed on peripheral blood lymphocytes. Chromosome preparation and GTG banding were done according to standard procedures [Liehr et al., 1995; Verma and Babu, 1998].
Growth parameters (length/height, head circumference, and weight) were evaluated by two trained physicians. All anthropometric measurements were attempted following the recommendations of the International Biological Publications, using standardized equipment [Hiernaux and Tanner, 1969; Hall et al., 1989]. They were recorded as the mean of three accepted consecutive readings. Measurements included body weight; using Seca scale approximated to the nearest 0.01 kg with minimal clothes for which no correction was made, length was measured using an infantometer for children <3 years and body height was measured without shoes using Holtain Stadiometer for children >3 years, and approximated to the nearest 0.1 cm. Measurement of maximum head circumference was taken using a non-stretchable tape from the occiput passing above but not including the brow ridge. Body mass index (BMI) was calculated as: [body weight (kg)/height or length (m2)]. Comparison between the studied TS patients and the Egyptian cross-sectional data standards [Ghalli et al., 2008] was performed.
Patients were divided into yearly age groups. Means and standard deviation (SD) of evaluated growth parameters were calculated for each age group. They were graphically smoothed using polynomial fitting equation and plotted. Also, means for the three anthropometric measures comparing females with Turner syndrome with normal Egyptian standards were graphically plotted using polynomial equation for smoothing. Baker et al.  found that polynomial curves adequately represent growth pattern. We plotted growth curves for height, head circumference, weight and BMI from the age of 6 months to 24 years with means and ±2 SD. This study was performed according to the Helsinki declaration and was approved by the Ethical Research Committee of National Research Centre.
Table I presents the general characteristics and karyotype analysis in the studied female patients with TS. Short stature (height ≤2 SD) was detected in 96.8% of patients older than 6 years. Figure 1 presents the height growth charts for TS patients compared to the mean height for Egyptian female standards. Height values were below the mean standards in TS patients. No height spurt was noticed in TS patients compared to normal Egyptian females at the age of puberty. Figures 2 and 3 present the weight and BMI growth charts for TS patients compared to the mean for Egyptian female standards. Weight and BMI values were higher than the mean standards in TS patients starting at the age of 2.5 years onwards. There was no difference in head circumference measurements between TS and Egyptian controls (Fig. 4).
Table I. The General Characteristics and Karyotype of Egyptian Females With Turner Syndrome
Increased carrying angle
Wide spaced nipples
Short fourth metacarpal
Delayed bone age
Lymphedema of hands and feet
Mosaic 45,X/46,XX karyotype
Turner syndrome is commonly caused by loss of the entire X chromosome. In our study, karyotype revealed monosomy 45X in 59.1%. Scales and Weber  reported monosomy in 50% of TS patients, while de Araújo et al.  and Schonhoff et al.  detected monosomy in 64.3%.
The special characteristics of the studied TS patients were reported in different studies [Keizer-Schrama, 2007; Hjerrild et al., 2008; Dumancic et al., 2010]. Lymphedema was detected in 12.9% of our patients. Morgan  delineated that at birth, diagnosis of TS may be made after the identification of edematous hands and feet. Increased carrying angle was found in 47.3% of our patients. de Araújo et al.  stated that increased carrying angle was present in 20% of TS patients. Increased carrying angle seems more prevalent in Europian patients, as it was presented in half of Bannink et al.  TS cases. Kavoussi et al.  and Scales and Weber  emphasized that TS patients undergo ovarian failure prior to or around the time of puberty. This elucidated delayed puberty in 12.9% and amenorrhea in 11.8% of the studied patients.
In our study, short stature was present in 96.8% of patients. There are reports in the literature indicating the prevalence of stunting between 84% and 100% [El-Roubi et al., 2001; de Araújo et al., 2010]. The height of the patients in this study was similar to that of the American patients [Davenport et al., 2002] which indicates similarity between the two populations. Comparing the height of our TS patients with Egyptian female standards [Ghalli et al., 2008], showed that TS females grew more slowly with no apparent pubertal growth spurt [Morgan 2007; Hsu et al., 2008]. This finding may be due to three principal factors: a slow growth rate of the infancy component, a slow growth rate at the onset of the childhood component, and delayed onset of the childhood component [Davenport et al., 2002]. Recent studies [Scales and Weber, 2010; Zenaty et al., 2011] elucidated that short stature occurred in 98% of girls with TS. When comparing the mean heights of TS Egyptian patients with TS patients in UK and European patients, Egyptian patients showed slightly lower values [Lenko et al., 1979; Pelz et al., 1982; Ranke et al., 1983; Lyon et al., 1985]. Differences between the present study and other worldwide studies can be attributed to various genetic, racial, geographical and nutritional factors.
Overweight was detected in 36.6% of our patients, similarly de Araújo et al.,  and Baldin et al. [2011, 2012], found that patients with TS have an increased risk of weight gain. Moreover, Blackett et al.  and El-Roubi et al.  delineated that TS girls have increased BMI relative to unaffected girls. There was no significant change in head circumference of the studied TS patients and the Egyptian controls. This coincides with the findings of Baldin et al. .
Local reference growth curves are more appropriate to use than International standards. The presented growth curves of Egyptian females with Turner syndrome should be used for follow up of Egyptian patients since the body structure is quite different among different ethnic groups.