Gonadal Dysgenesis Due to Isochromosome Formation of Long Arm ...

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