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Indian Pediatr 2011;48: 402-404 |
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Mosaic Pentasomy X/Tetrasomy X Syndrome and
Premature Ovarian Failure |
Andy Wood, Lora Kleis, Helga Toriello* and Ayse Pinar Cemeroglu
From Helen DeVos Children’s Hospital, Pediatric Endocrinology and
Diabetes; and *Spectrum Health, Genetic Services,
Grand Rapids, MI, 49503, USA.
Correspondence to:
Ayse Pinar Cemeroglu, Pediatric Endocrinologist and Associate Professor of
Pediatrics at MSU, Spectrum Health, Helen DeVos Children’s Hospital, 230
Michigan Street NE, Suite 101, MC 77,
Grand Rapids, Michigan, 49503, USA.
Email: [email protected]
Received: October 5, 2009;
Initial review: November 10, 2009;
Accepted: February 5, 2010.
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A 16 year-old girl with pentasomy X mosaicism (47,XXX(1)
48,XXXX(12)/49,XXXXX) presented with primary amenorrhea. She had
epicanthal folds, long philtrum, high-arched palate, facial asymmetry,
short webbed neck, low posterior hairline, mild scoliosis, cubitus
valgus, mental retardation and clinodactily. She was diagnosed with
osteoporosis and premature ovarian failure.
Key words: Osteopenia, Pentasomy X syndrome, Premature
ovarian failure, Tetrasomy X syndrome.
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Pentasomy
X syndrome is a very rare chromosomal disorder, first reported by
Kesaree and Woolley in 1963 [1]. It is estimated to 1/85,000 [2],
with less than 30 cases reported in the literature [3]. Since most
cases are 10 years of age or younger, gonadal function has
not been well described. In a few cases, delayed puberty and
dysfunctional ovaries have been reported [4-6].
Case Report
A 16-year-old girl with mosaic pentasomy X
syndrome presented to the pediatric endocrinology clinic with the
complaint of primary amenorrhea. She was diagnosed with mosaic
pentasomy X syndrome in the neonatal period because seizures and
hypotonia prompted a chromosome evaluation. The karyotype revealed
mosaic pentasomy, 47,XXX(1) 48,XXXX [12]/49,XXXXX [7]. Past medical
history included patent ductus arteriosus repair at age 7 days and
cholecystectomy for gallstones (nonpigmented) at age 13. She had
normal fasting lipid profile and normal oral glucose tolerance test.
The gallstone work-up revealed no apparent etiology. In early
childhood, she was noted to have developmental delay. She sat
without support at 9 months, walked at 18 months and had a
significant speech delay. She was toilet trained by 2.5 years of
age. The Woodcock-Johnson III tests of cognitive abilities at age 14
years showed mild to moderate cognitive impairment. The estimated IQ
was 65-70. Her first sign of puberty reportedly was breast
development at age 12, reaching Tanner stage IV between the ages of
14 and 15; however, she had not achieved menarche. She was in 9th
grade in special education, and was taking a mood stabilizer for
behavioral issues.
Physical examination revealed epicanthal folds,
long philtrum, high-arched palate, facial asymmetry, short webbed
neck, low posterior hairline, mild scoliosis, cubitus valgus,
limited supination of the forearms suggesting radioulnar synostosis,
and clinodactyly. She was 168.2 cm tall, weighed 62.5 kg (both at
the 75th percentile), had Tanner IV pubic hair and breast
development. Laboratory testing revealed a very high follicle
stimulating hormone (FSH) level of 104.7 mIU/mL (normal range: 3-22
mIU/mL), a luteinizing hormone (LH) level of 63.1 mIU/mL (normal
range: 2-11 mIU/mL) and an estradiol level of 23 pg/mL (normal
range: 24-400 pg/mL). Fragile X molecular analysis was negative.
Anti-ovarian antibody to test for autoimmune ovarian failure was
negative. Bone mineral densitometry (axial and appendicular scan)
showed osteoporosis, with a Z-score of -1.5 between L1 and L4
and a Z-score of -1.5 for total bone mineral density.
Subsequently, she was started on hormone replacement with an oral
contraceptive.
Discussion
Pentasomy X syndrome is a rare chromosomal
disorder characterized by five copies of the X chromosome resulting
in 49 total chromosomes. The most accepted explanation for this
occurrence is two nondisjunctions of the X-chromosomes during
meiosis. The first nondisjunctions occurs during meiosis I and
second in meiosis II resulting in four maternally inherited X
chromosomes and the fifth X-chromosome is provided by the father
[7-9].
The phenotype of the pentasomy X syndrome is
similar to those of Turner and Down syndromes including bilateral
transverse palmar creases [8], craniofacial anomalies, cognitive
impairment (average IQ of 50, range: 20 to 75), short stature,
skeletal and articular abnormalities [6] (talipes equinovarus,
radioulnar synostosis, clinodactyly of the fingers and toes, and
general laxity of joints leading to frequent dislocations)
and congenital heart defects [10] (patent ductus arteriosus
and ventricular septal defect). These girls typically have speech
problems, difficulty communicating and a shy personality [3].
Tetrasomy X syndrome is slightly more commonly
seen (40 cases) than pentasomy X syndrome. The findings in general
are similar but only milder than pentasomy X syndrome, including
milder facial abnormalities, taller stature and higher IQ with an
average of 60 [3].
Pentasomy X/tetrasomy X mosaicism is even less
frequently reported in the literature than pentasomy X [9]. The
mosaicism in petasomy X syndrome is the result of a presumed
post-fertilization loss of one X chromosome. In our patient,
although the karyotype analysis showed higher percentage of 48XXXX
than 49 XXXXX cell line in peripheral blood, based on the mechanism
involved in this chromosomal abnormality, one can conclude that the
initial abnormality was pentasomy X. Furthermore, mosaicism is known
to vary in percentage in different tissues in the body. It has been
reported that patients with 48XXXX/49XXXXX mosaicism have similar
findings to those with pentasomy X [5,9]. Fertility in pentasomy X
is suspected to be compromised, but insufficient data are available
to validate this as most patients reported are younger than 11 years
of age. The girl with pentasomy X mosaicism reported by Gordon and
Paulsen [5] had premature menopause at age 17. The other three
girls, two of whom were age 10 years and one of whom was 15 years,
were all prepubertal, but one of the 10 year-old girls had high
gonadotropin levels similar to our patient [4], suggesting premature
ovarian failure. In the other two cases [3,6], gonadotropin levels
were not reported. In tetrasomy X syndrome, 50% of the adult females
had normal fertility, menarche and menopause and 50% had menstrual
irregularities [3].
To conclude, patients with pentasomy X syndrome,
should undergo early screening for ovarian failure during early
adolescence. Hormone replacement should be considered at the normal
age of puberty to prevent severe osteoporosis.
Contributors: All authors contributed to
diagnosis of case, review of literature and writing the manuscript.
Funding: None.
Competing interests: None stated.
References
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1963;63:1099-1103.
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Pentasomy X and hyper IgE syndrome: co-existence of two distinct
genetic disorders. Eur J Pediatr. 1999;158:723-6.
3. Linden MG, Bender BG, Robinson A. Sex
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XXXXX syndrome. Report of a case with 48 XXXX/49XXXXX mosaicism.
Acta Pediatr Scand. 1979;68:769-71.
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