48,XYYY: A RARE CASE REPORT Sabnis AS, Bhusare D *Corresponding Author: Dr. Anjali S Sabnis, M.D. Professor and head, Department of Anatomy, MGM
Medical College and Hospital, Kamothe, Navi Mumbai - 410209. India, Mobile no: 9820493036, email
address: dranjus2003@yahoo.com page: 103
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DISCUSSION
The present case is of a 4 year old male child with
hypospadias and cryptorchidism on right side, showing two
extra Y chromosomes. The presence of supernumerary Y
chromosomes is a rare phenomenon. The mechanism by
which a patient gets two extra Y chromosomes is not clear.
The most likely explanation appears to be one originally
proposed by Townes et al. that non-disjunction in spermatogonia
mitosis followed by 2nd non-disjunction of one
Y chromosome in meiosis would result in the formation of
sperm bearing three Y chromosomes [4]. Sperm containing
three Y chromosomes could theoretically be produced by
secondary non-disjunction or anaphase lagging in meiosis
II from a XYY primary spermatocyte [5]. Fertilization of
normal ovum by YYY sperm would probably give rise to the
XYYY condition. In the present case, cytogenetic analysis
of the peripheral blood of the father of the child showed a
normal male chromosomal pattern, indicating the absence
of inheritance for the XYY karyotype in the present case.
The XYYY pattern is mostly observed with a mosaic
pattern of XYY, XY and/or X, [6-18] and can also be seen
as a single clone. Out of 15 cases, a mosaic pattern is seen
in 7 cases, and pure XYYY is seen in 8 cases (Tables 1 and
2). The range of age in which pure XYYY and mosaic pattern
appears is from 13th week to 53 years. Individuals with
XYYY have widely varying phenotypes with regard not
only to physical signs but also to brain functions and cognitive
performance [19]. XYYY is associated with clinical
features like bossy behavior, argumentative, loud voiced,
friendless [4], frequent respiratory infections, inguinal
hernia, hypoplastic middle phalanges with a single palmar
crease [4]. In one of the cases, emotional and educational
difficulties were noted along with myopia at the age of
5. Behavioral changes such as aggressiveness, violence
and uncontrollable acts were observed. These deteriorated
gradually [20]. Adult males with 48,XYYY are tall , having
incurved little fingers of both hands, small testes with a
lack of sexual desire, testicular biopsy with atrophic seminiferous tubules without spermatogenesis [10]. A 32 year
old male with 48,XYYY showed semi-Klinefelter characteristics
such as a tall stature, teeth dysmorphology, long
length of fingers, and partial deformity of the joints [18].
A 19 year old male with 48,XYYY showed dysmorphic
features, mental retardation, and abnormal psychosocial
functioning [19]. A 5 year old boy with 48,XYYY showed
a mosaic pattern 45XO/48,XYYY with hypospadias but
showed normal intelligence [7]. A 37 year old obese man
with dysplasia of right hip, mental retardation, behavior
disturbances, aggressiveness, sexual impulsions and fibrohyalination
in the testis showed a mosaic pattern of
46,XY/48,XYYY [13]. A 32 year old male patient with
complaint of infertility showed clinical features of long
length of fingers and toes, partial deformity of joints and
nails, mental health problems, teeth dysmorphology and
a karyotype analysis revealed 48,XYYY [21]. 48,XYYY
was observed in a fetus after intra cytoplasmic sperm injection
(ICSI) [17] and a mosaic pattern of two cell lines
45,X/48,XYYY was observed in the amniotic fluid culture
of an 18 week old fetus [22]. Occasional aggressive
outbursts and poor emotional stability seem to be fairly
consistent among 48,XYYY males [10 ].
In the present case, the 4 year old child showed normal
phenotypic features with a height 113 cm and weighing
in at 17 kg. The child maintains a good intellectual
status, as shown by his school performance but shows an
aggressive nature. There was an absence of dental abnormalities
and other clinical features except hypospadias and
cryptorchidism. The proband was born via a third degree
consanguineous marriage and has one brother which is
phenotypically and genotypically normal. The karyotype
of lymphocytes show 48,XYYY and a FISH analysis
shows a mosaic pattern of four different cell lines. 7% of
the cells show a normal chromosomal pattern while 73%
of the cells show 48,XYYY. 7% of the cells show 47,XYY
and 13% of the cells show a 45,X pattern. The ratio of
aneuploid cells to euploid cells decides the consequence
of a mosaic pattern. The more aneuploid cells there are,
the more abnormal the clinical features. This includes
the result that the euploid cells are fewer in number, as
one of the abnormal clinical features. In the present case, 93% of the cells are aneuploid cells, while 7% of the cells
are euploid cells. The clinical features of hypospadias,
cryptorchidism, and aggressiveness may be related to the
supernumerary Y chromosome. Only one case of XYYY
is reported in a fetus and the case of 4 years old male child
reported is the first live case with XYYY in India .
Genetic counselling of the adult patient and the parents
(in case of pediatric age) is strongly recommended. The
follow up of the pediatric group of patients will be helpful
to study their psychological, sexual, and personality development,
thus adding to the understanding of phenotypic
features and its relation to presence of triple Y chromosome .
Acknowledgment: Authors acknowledge Dr. Arundhati
Athalye and Mr. Rupesh Sanap from Jaslok Hospital for
carrying out FISH procedure and doing analysis.
The authors alone are responsible for the content and
writing of this article
Declaration of Interest. The authors report no conflicts
of interest. The authors alone are responsible for the
content and writing of this article.
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