Gonadal Dysgenesis Due to Isochromosome Formation of Long Arm ...
Gonadal Dysgenesis Due to Isochromosome Formation of Long Arm ...
Gonadal Dysgenesis Due to Isochromosome Formation of Long Arm ...
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© JAPI • april 2013 • VOL. 61 57<br />
Case Report<br />
<strong>Gonadal</strong> <strong>Dysgenesis</strong> <strong>Due</strong> <strong>to</strong> <strong>Isochromosome</strong> <strong>Formation</strong><br />
<strong>of</strong> <strong>Long</strong> <strong>Arm</strong> <strong>of</strong> X Chromosome<br />
Asish Kumar Basu * , Rudrajit Paul ** , Ramtanu Bandyopadhyay *** , Srabani Chakrabarti ****<br />
Abstract<br />
<strong>Isochromosome</strong> involving the long arm <strong>of</strong> X chromosome is a rare structural rearrangement <strong>of</strong> the X chromosome,<br />
leading <strong>to</strong> <strong>Gonadal</strong> dysgenesis. These patients present as phenotypic females with amenorrhea and growth<br />
failure. Often other associated features like endocrine abnormalities and skeletal deformities are found. They are<br />
chromatin positive cases and are only diagnosed by karyotyping. Hashimo<strong>to</strong>’s thyroiditis is a rare association<br />
with isochromosome X.<br />
Fig. 1 : Figure <strong>of</strong> the patient showing the stages <strong>of</strong> secondary sexual<br />
character development.<br />
*<br />
Assistant Pr<strong>of</strong>essor, Dept. <strong>of</strong> Endocrinology, ** Post-graduate Trainee,<br />
***<br />
Associate Pr<strong>of</strong>essor, Dept. <strong>of</strong> Medicine, Medical College, 88,<br />
College Street, Kolkata-700073; **** Assistant Pr<strong>of</strong>essor, Department<br />
<strong>of</strong> Pathology, IPGMER and SSKM Hospital, 244, Acharya Jagadish<br />
Chandra Bose Road, Kolkata-700020<br />
Received: 30.06.2010; Accepted: 17.04.2012<br />
Introduction<br />
<strong>Isochromosome</strong> involving the long arm <strong>of</strong> X chromosome is<br />
a structural rearrangement <strong>of</strong> the X chromosome accounting<br />
for 15% cases <strong>of</strong> <strong>Gonadal</strong> dysgenesis. These patients present<br />
as chromatin positive cases. 1 These cases <strong>of</strong>ten present<br />
with amenorrhea. 2 A case <strong>of</strong> <strong>Gonadal</strong> dysgenesis due <strong>to</strong><br />
isochromosome <strong>of</strong> X is reported here.<br />
Case Report<br />
An 18 year old girl attended endocrinology OPD for<br />
evaluation <strong>of</strong> primary amenorrhea. She had a his<strong>to</strong>ry <strong>of</strong><br />
hypothyroidism. She had stunted growth compared <strong>to</strong> the peers.<br />
She was born out <strong>of</strong> a non-consanguinous marriage and there<br />
was no similar family his<strong>to</strong>ry <strong>of</strong> primary amenorrhea. Physical<br />
examination revealed unambiguous female phenotype with<br />
short stature (142 cm; less than 3 rd percentile for age). There<br />
were short 4 th metatarsals, with mild P<strong>to</strong>sis <strong>of</strong> right eye. There<br />
were no evidences <strong>of</strong> shield chest, webbing <strong>of</strong> neck or cubitus<br />
valgus. Her breast development was tanner stage 5 and axillary<br />
and pubic hair was tanner stage 3 / 4 (Figure 1). Examination <strong>of</strong><br />
cardiovascular system revealed no evidence <strong>of</strong> bicuspid aortic<br />
valve or coarctation <strong>of</strong> aorta; there were no signs <strong>of</strong> wasting,<br />
chronic disease, tuberculosis, or hemolytic anemia. She also had<br />
a firm goiter with clinical features <strong>of</strong> hypothyroidism.<br />
Labora<strong>to</strong>ry investigations revealed: hemoglobin 10 gm/<br />
dl, Fasting Blood Sugar and Post Prandial Blood Sugar were<br />
normal. Serum fT3, fT4 and TSH were 0.8 ng/ml, 3.6 microgm/<br />
dl and 24 μU/ml (normal: 0.34 -4.25) respectively, consistent<br />
with primary hypothyroidism. Anti- TPO was present in<br />
>1:400 dilution and FNAC from thyroid gland showed features<br />
consistent with hashimo<strong>to</strong> thyroiditis. Serum LH and FSH levels<br />
were 42 mIU/ml (normal: 2-15) and 70 mIU/ml (normal: 3-20)<br />
respectively determined by radioimmunoassay. Serum GH levels<br />
following insulin hypoglycemia revealed no abnormality. Pelvic<br />
sonography revealed bilateral streak gonads and hypoplastic<br />
uterus. Buccal smear was positive for sex chromatin. The<br />
karyotype was 46, XXqi i.e. an X chromosome consisting <strong>of</strong> two<br />
long arms and no short arms (Figure 2). This was found in all the<br />
cells studied. The karyotype analysis <strong>of</strong> the parents was normal.<br />
Discussion<br />
Patients with long arm X isochromosome invariably present<br />
with short stature and streak gonads as in our case. Some<br />
© JAPI • april 2013 • VOL. 61 283
58 © JAPI • april 2013 • VOL. 61<br />
with long arm X isochromosome. 5 Our patient had hashimo<strong>to</strong><br />
thyroiditis with clinical hypothyroidism which is a rare<br />
association with isochromosome X with <strong>Gonadal</strong> dysgenesis. 6<br />
Conclusion<br />
In cases <strong>of</strong> <strong>Gonadal</strong> dysgenesis it is important <strong>to</strong> carry out<br />
karyotyping and endocrine evaluation <strong>to</strong> know the underlying<br />
pathology. This helps in proper hormonal therapy and also<br />
genetic counseling.<br />
Fig. 2 : Figure <strong>of</strong> the karyotype <strong>of</strong> the patient with red arrow<br />
showing the isochromosome X.<br />
<strong>of</strong> them may menstruate, although most patients like ours,<br />
present with primary amenorrhea. 2,3 The somatic stigmata<br />
<strong>of</strong> Turner’s syndrome are less evident. Features that are<br />
commonly present include short stature, overweight, scant<br />
secondary sexual characteristics, sterility, strabismus, nevi and<br />
cubitus valgus. 4 Coarctation <strong>of</strong> aorta and lymphedema <strong>of</strong> the<br />
hands are conspicuously absent, as in the present case. Slight<br />
webbing <strong>of</strong> neck has been occasionally reported. Hashimo<strong>to</strong><br />
thyroiditis, impaired glucose <strong>to</strong>lerance and inflamma<strong>to</strong>ry bowel<br />
disease have been reported <strong>to</strong> occur more frequently in patients<br />
References<br />
1. Lindsten J, Fraccaro M, Ikkos D, Kaijser K, Klinger HP, Luft R.<br />
Presumptive iso chromosomes for the long arm <strong>of</strong> X in man. Analysis<br />
<strong>of</strong> five families. Annals <strong>of</strong> Human Genetics 1963;(4):26:383- 406.<br />
2. Hodgson S, Chiu D, Polani P. Sexual development <strong>of</strong> patients with<br />
isochromosomes for the long arm <strong>of</strong> X chromosome. Hum Genet<br />
1981;58:176-178.<br />
3. Henry M Kronenberg, Shlomo Melmed, Kenneth S Polonsky, P<br />
Reed Larsen. Williams’s text book <strong>of</strong> endocrinology. 11 th edition.<br />
2008. Chapter 19.<br />
4. Neil Senzer, Thomas Ace<strong>to</strong>, Jr, Maimon M Cohen, Anke A. Ehrhardt,<br />
Valiolah Abbassi, Vincent J Capraro. <strong>Isochromosome</strong> X. Clinical<br />
and Psychological Findings. Am J Dis Child 1973;126:312-316.<br />
5. Malcolm A Ferguson-Smith. Karyotype-phenotype Correlations<br />
in <strong>Gonadal</strong> <strong>Dysgenesis</strong> and Their Bearing on the Pathogenesis <strong>of</strong><br />
Malformations. J Med Genet 1965;2:142–155.<br />
6. Hochberg Z. Subclinical Hashimo<strong>to</strong>’s thyroiditis in <strong>Gonadal</strong><br />
dysgenesis. Isr J Med Sci 1980;16:847-8.<br />
284 © JAPI • april 2013 • VOL. 61