Clinical Brief

Turner Syndrome and its Variants

R. Bharath, A.G Unnikrishnan, M.V Thampy1, Alka Anilkumar1, B Nisha, V.P Praveen, Vasantha Nair,
R.V. Jayakumar and Harish Kumar

Department of Diabetes and Endocrinology, Amrita Institute of Medical Sciences, Kochi, Kerala. 1Department of
Human Cytogenetics, Amrita Institute of Medical Sciences, Kochi, Kerala, India

ABSTRACT
Case records of female patients with karyotype proven turner syndrome were analyzed. 11 patients had classic Turner
karyotype (Group 1) and 13 patients had karyotype suggestive of one of the variants of Turner syndrome (Group 2). There
was a median difference of 3 years between the age of presentation and the age of diagnosis in Group 2. Out of the thirteen
patients in Group 2, 4 had no clinical stigmata of Turner Syndrome; the rest (n=9) had one or more of the typical clinical
stigmata of Turner Syndrome. One patient with a complex mosaic karyotype also had an intracranial medulloblastoma. One
patient in each group had coarctation of the aorta. 5 patients in Group 1 and 3 patients in Group 2 had primary hypothyroidism
and received levothyroxine. The median Thyroid Stimulating Hormone levels were significantly higher among patients in group
1 than in group 2. [Indian J Pediatr 2010; 77 (2) : 193-195] E-mail: unnikrishnanag@aims. amrita.edu, u_ag@yahoo.com

Key words: Turner Syndrome; Karyotype; Variants; Medulloblatoma; Hypothyroidism

Turner Syndrome (TS) is the consequence of complete or
partial absence of one X chromosome in a phenotypic
female usually accompanied by short stature and gonadal
dysgenesis. The classic form of TS is associated with a
45,X karyotype and occurs in approximately one half of
individuals with this condition. Mosaic forms of TS (45,X/
46,XX) account for one fourth of Turner patients, whereas
the rest have structural abnormalities of the X
chromosome.1 We present the clinical, morphological and
hormonal characteristics of patients with TS diagnosed in
our institution.
and audiogram were performed in all patients. Serum
FSH and LH were done in patients who were 12 yr of age
and above. The technique of karyotype analysis was
performed according to guidelines from the International
System for Human Cytogenetic Nomenclature (ISCN,
2005). Serum FSH, LH, TSH and Free T4 were done by
Electrochemiluminiscent Assay (Elecsys). Statistical
analysis was done using SPSS 11.0. Comparison of
parameters (clinical & lab) among patients with TS due to
classic karyotype and variant karyotype was done by
Mann-Whitney U test.

MATERIAL AND METHODS RESULTS

The case records of female patients who underwent
karyotyping of peripheral blood lymphocytes were
analyzed in our tertiary care institution from January 2003
to December 2007. All these patients underwent testing as
a part of evaluation of short stature (height less than 2SD
for the chronological age) along with either of the
following: primary or secondary amenorrhea, or any two
of the stigmata of gonadal dysgenesis.2,3 Thyroid function
tests (Free T4, TSH), ultrasound examination of
genitourinary system, 2-Dimensional echocardiography
Correspondence and Reprint requests : Dr Unnikrishnan AG,
Professor, Department of Endocrinology and Diabetes, Amrita
Institute of Medical Sciences, Elamakkara PO, Cochin-682026, India
[DOI-10.1007/s12098-009-0226-7]
[Received May 12, 2008; Accepted October 08, 2008]
Twenty four patients with TS were identified during the
five year period. Among them, 11 patients had classic
Turner karyotype (Group 1) and 13 patients had
karyotype suggestive of one of the variants of TS (Group
2). Median duration of follow-up was 1.60yr (range
4months –5yr). In patients < 19 yr of age (n=9) the mean
height was 129.74±14.36cm. (range 110-152cm.) and the
height SD score was -2.64±0.47(range –2 to –3SD). Patients
with primary hypothyroidism were managed with
levothyroxine supplementation to maintain Free T4 and
TSH levels within the normal range.
All the patients had a height velocity below the 5 th
percentile in the normal female growth chart. Due to
financial constraints, only 3 patients in Group 2 could
afford growth hormone (GH) therapy. One patient
received it for only 6 months, at the end of which it was

Indian Journal of Pediatrics, Volume 77—February, 2010 193

 R. Bharath et al

TABLE 1. Turner Syndrome Variants- Distribution of Karyotypes (Group 1) and rest had variant karyotype (Group 2).
in 13 Women Structural abnormalities of X chromosome were more
Karyotype group Karyotype No. of common in Group 2 than 45,X/46,XX karyotype (84.62%
patients vs15.38%). In previous studies done by Khadilkar et al.4
and Suri et al. 5 incidence of structural abnormalities
Isochromosome Mosaic 45X/46Xi(Xq) 1 among the TS variants were reported to be 72.7% and 56%
46XX Mosaic 45X/46XX 2
Ring X Mosaic 45X/46Xr(X) 2
respectively. These differences are due to the fact that the
Isochromosome X 46Xi(Xq) 2 studies are not population based. The median TSH levels
Interstitial were significantly higher (p=0.028) among patients with
Long-arm deletions 46,X, Xq 3 TS due to classic karyotype than those due to variant
Complex Mosaic 45X/46XX/47XXX 1 karyotype. One of the previous studies on thyroid
Autosomal Translocation 46XX t(9:X) 1
autoimmunity in TS showed an increased incidence of
Inversion 46XX,inv (9)
(p11q21.1) 1 thyroid autoimmunity and primary hypothyroidism in
women with an isochromosome-X karyotype compared
with other karyotypes.6
TABLE 2. Clinical Features of Patients in Group 1 and Group 2
So far, there are only 2 cases reported of
Clinical Features Classic Turner Turner variants Medulloblastoma associated with TS. One was a
(n=11) (n=13)
(Group 1) (Group 2)
cerebellar Medulloblastoma in a 16-yr-old girl with 45,X
karyotype.7 The second report was of a 9 yr old girl who
Primary Amenorrhea 7 5 had a Medulloblastoma diagnosed at autopsy.8 We had
Secondary Amenorrhea 1 3 one patient who was operated for an intracranial
High arched palate 3 3
Medulloblastoma at the age of 8 yr. The diagnosis of TS
CSOM 1 2
Wide Carrying angle 7 6 was made much later when she was evaluated for short
Short Metacarpals 1 4 stature and primary amenorrhea. Karyotyping performed
Pigmented Neavi 1 3 then showed 45 X/47 XXX/47XXX, der (12) +14, -15. Since
Primary hypothyroidism 5 3 the girl was diagnosed to have TS 7 years after successful
Coarctation of Aorta 1 1
removal of Medulloblastoma, we did not have the
Medulloblastoma 0 1
Bicuspid Aortic valve 2 0 chromosomal analysis of the tumor tissue.
Renal Anomalies 2 0
The median age of presentation in Group 2 was 14yr
(Range 8-18yr) and the median age when diagnosis was
TABLE 3. Comparison of Parameters(median) Among Patients confirmed by karyotyping was 17yr (Range 8-32yr), there
with Turner Syndrome Due to Classic Karyotype and being a delay of 3 yr between the presentation and
Variant Karyotype
diagnosis. This delay leads not only to late initiation of
Parameter Classic Turner P value growth and puberty promoting therapy but also to failure
Turner variants in timely screening for the possible cardiac, renal, thyroid,
(n=11) (n=13) auditory, psychosocial and intellectual dysfunction that
can potentially be present in TS.
Age of presentation
(yrs) 16 14 0.80 In the present series, 2 patients who were started on
Age of diagnosis GH treatment had a mean height gain of 2.67 cms and
(yrs) 16 17 0.589
2.11 cms per year. In the study done by Khadilkar et al4,
FSH (m IU/mL) 106.35 114 0.97
LH (m IU/mL) 29.09 33.54 0.25 when GH treatment was given to 16 girls with TS for 1
TSH (µ IU/mL) 7.66 3.67 0.028 year, the gain in height was approximately 2.4cm. Our
patient who had GH therapy for 5 years had the final
height gain of 10.56cms than her predicted height before
stopped, because of unsatisfactory response. In the other treatment.
two patients, Recombinant human Growth Hormone was
started at a dose of 0.375mg/kg/week. These patients Early recognition of Turner Syndrome and timely
were followed up for 18 months and 5 years during which investigations nevertheless should help in improving the
period height velocity was carefully recorded. Their mean quality of life of these individuals by potentially
gain in height was 2.67cms/yr. and 2.11cms/yr improving the adult height in those who respond to GH
respectively. therapy and in initiating sex hormone replacement. Also,
early detection and management of co-existing illnesses
(like coarctation) may be life saving for these patients.
DISCUSSION
Contributions: R. Bharath; involved in collection of data, analysis
and preparation of the manuscript. A.G. Unnikrishnan; involved in
In this case series 45.83% of patients had classic karyotype clinical management of patients, collection of data, analysis and

194 Indian Journal of Pediatrics, Volume 77—February, 2010

 Turner Syndrome and its Variants
preparation of the manuscript. M.V. Thampy and Alka Anilkumar
- involved in the analysis and reporting of karyotype studies of
turner patients. B. Nisha and V.P. Praveen - involved in
management of turner patients, analysis and correction of
manuscript. Vasantha Nair, R.V. Jayakumar and Harish Kumar -
involved in management of turner patients, analysis and correction
of manuscript.
Conflict of Interest: None.
Role of Funding Source : None.
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