Volume 04 Issue 06-2024
95
International Journal of Medical Sciences And Clinical Research
(ISSN
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2771-2265)
VOLUME
04
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06
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AGES
:
95-104
OCLC
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1121105677
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ABSTRACT
A clinical case of a patient with multiple myeloma with Shereshevsky-Turner syndrome was analyzed. The
effectiveness of treatment according to the VRD protocol in the first line in the treatment of multiple myeloma with
concomitant congenital mutations was assessed. An early relapse of the disease was revealed, requiring
polychemotherapy with monoclonal antibodies.
KEYWORDS
Multiple myeloma, chemotherapy, Turner syndrome, chromosome.
INTRODUCTION
Shereshevsky-Turner syndrome is a genetically
determined pathology that develops exclusively in
girls. In this chromosomal disease, the second of the
sex X chromosomes is lost. In some cases, only part of
it is missing. Changes in the chromosome set also
manifest themselves phenotypically (1,5,9,10). The
Research Article
MULTIPLE MYELOMA AND SHERSHEVSKY TERNER'S SYNDROME
(CLINICAL CASE)
Submission Date:
June 20, 2024,
Accepted Date:
June 25, 2024,
Published Date:
June 30, 2024
Crossref doi:
https://doi.org/10.37547/ijmscr/Volume04Issue06-15
Maxamadalieva G.Z.
Republican Specialized Scientific And Practical Center Of Hematology, Uzbekistan
Gulmirzaev J.A.
Republican Specialized Scientific And Practical Center Of Hematology, Uzbekistan
Xamidova F.I.
Republican Specialized Scientific And Practical Center Of Hematology, Uzbekistan
Isxakov E.D.
Republican Specialized Scientific And Practical Center Of Hematology, Uzbekistan
Journal
Website:
https://theusajournals.
com/index.php/ijmscr
Copyright:
Original
content from this work
may be used under the
terms of the creative
commons
attributes
4.0 licence.
Volume 04 Issue 06-2024
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(ISSN
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VOLUME
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OCLC
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prevalence of the anomaly is quite high - 1 case per 2
–
2.5 thousand newborn girls. The pathology is one of
the three most common genetic diseases along with
Klinefelter syndrome and Down disease (2,7,12).
Shereshevsky-Turner syndrome was described in 1925
by the Soviet endocrinologist N.A. Shereshevsky, who
believed that it was caused by underdevelopment of
the gonads and the anterior pituitary gland and was
combined with congenital malformations of internal
development. In 1938, Turner identified a triad of
symptoms characteristic of this symptom complex:
sexual infantilism, skin pterygoid folds on the lateral
surfaces of the neck and deformation of the elbow
joints (3,4,13). The following chromosomal aberrations
are possible, leading to the STS phenotype:
• X monosomy (45, XO);
• Partial or complete deletion
of the short arm of the
X chromosome (delXp);
• Complete deletion of the long arm of the X
chromosome (delXq);
• Isochromosome of the long arm of the X
chromosome (i (Xq));
• ring X chromosome (r (X));
• marker chromosome (46, X + m);
• mosaicism, that is, the presence of more than two
cell lines in one person, most often 45,X/46,XX and
45,X/46,XY.
Depending on the size of the lesions, clinical symptoms
differ. In cases of mosaicism, the full range of
symptoms may also be absent (1,2,3). Mapping the X
chromosome and studying some of its genes made it
possible to associate some features of TTS with
dysfunction of certain genes. It also turned out that the
variability of the cytogenetic image is expressed in the
variability of the phenotype of patients with STS, which
is important in predicting the course of the disease
(2,7,12,8).
According to the literature, a clear connection
between the occurrence of Shereshevsky-Turner
syndrome and age and any diseases of the parents has
not been identified. In the embryo, primary germ cells
are formed in almost normal numbers, but in the
second half of pregnancy they undergo rapid
involution (reverse development), and by the time the
child is born, the number of follicles in the ovary is
sharply reduced compared to the norm or they are
completely absent. This leads to severe deficiency of
female sex hormones, sexual underdevelopment, and
in most patients to primary amenorrhea (absence of
menstruation) and infertility (6,9,10,13). The resulting
chromosomal abnormalities are the cause of
developmental defects. It is also possible that
concomitant autosomal mutations play a certain role in
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the appearance of developmental defects, since there
are conditions similar to Shereshevsky-Turner
syndrome, but without visible chromosomal pathology
and sexual underdevelopment. Other pathological
findings are consistent with the clinical presentation.
The most important changes in the osteoarticular
system are shortening of the metacarpal and
metatarsal bones, aplasia (absence) of the phalanges
of the fingers, deformation of the wrist joint, and
osteoporosis of the vertebrae. Radiologically, in
Shereshevsky-Turner syndrome, the sella turcica and
the bones of the cranial vault are usually not changed
(3,6,8). All regions of the world and culture are
affected by this pathology approximately equally. It is
estimated to occur in 3% of all human fetuses.
However, only 1% of these fetuses survive birth. Normal
skeletal development is inhibited due to a wide variety
of factors, mainly hormonal. The average height of a
woman with STS without growth hormone treatment
is 140 cm. Patients with mosaic STS can reach a normal
average height. Due to insufficient estrogen
production, many people with TTS develop
osteoporosis. This can further reduce height and also
worsen the curvature of the spine, which can lead to
scoliosis. It also leads to an increased risk of bone
fractures (4,6,7,9).
About a third of all women with STS have one of three
kidney pathologies:
• One horseshoe
-shaped kidney on one side of the
div (instead of the usual two)
• Incorrect urine collection system
• Poor blood flow to the kidneys
Some of these conditions can be corrected with
surgery. Even with these abnormalities, the kidneys of
most women with STS function normally. However, as
noted above, kidney problems can be associated with
hypertension.
Approximately one third of all women with TTS have
thyroid
disease
(10,11,
23).
This
is
usually
hypothyroidism, specifically Hashimoto's thyroiditis.
Once detected, it can be easily treated with thyroid
hormones. Women with TTS have a moderately
increased risk of developing diabetes in childhood and
a significantly increased risk of developing diabetes in
adulthood (1,5,7) . A rare type of TTS, known as Ring-X
Turner syndrome, is associated with mental
retardation in 60% of cases. This type accounts for
about 2
–
4% of all cases of STS (6).
People with TTS are almost always infertile. Although
some women with TTS have successfully conceived
and survived pregnancy, it is very rare and usually
occurs in those women whose karyotype is not 45, X0.
The literature does not describe a case of multiple
myeloma in patients with STS.
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Purpose of the study: To analyze a clinical case of a
patient with multiple myeloma with Shereshevsky-
Turner syndrome
Patient V., 45 years old (Russian language teacher)
with Shereshevsky-Turner Syndrome (TST) complete X-
monosomy, was admitted to the Republican
Specialized Scientific and Practical Medical Center of
Hematology with complaints of general weakness,
dizziness, bone pain, decreased appetite, and
palpitations.
Karyotype 45.XO
Symptoms
Frequency by
occurrence %
In
our case
Intelligence preserved
50-60
+
Stunting
98
+
General dysplasticity (abnormal physique)
92
+
Lymphostasis (swelling) of the arms and legs
24
+
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Barrel chest and widely spaced nipples
75
+
Neck shortening
63
+
Low hairline at the back of the head
57
-
Low-set ears, ear deformation
46
-
Infertility
100
+
Vestigial ovaries
80-100
+
Amenorrhea
80-100
+
Small nails
60-79
-
Specific facial features
60-79
-
Wing-shaped folds of skin in the neck area
46
+
• Bicuspid aortic valve
50
-
High waist-to-hip ratio (hips not much larger than
waist)
80-100
-
Height below 140 cm.
80-100
160
см
The fourth metacarpal may be unusually short,
as may the fifth.
40-59
+
Osteoporosis and scoliosis.
40-50
+
bone fractures.
-
+
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According to the literature on cardiovascular
malformations, complications of aortic dilatation are
usually associated with a 45.X karyotype, but in our
case, no pathology with cardiovascular pathology was
identified.[27].
Survey results:
In the hemogram dated 08/03/23: hemoglobin 52.0 g/l,
erythrocytes 1.70 million, c.p.-0.9, leukocytes 5.83
thousand/μl, platelets 30.0 thousand/μl, p.o.
-6.0, s.o. -
45.0, lymphocytes 45.0 thousand/μl, mon.
-4.0%, ESR-
20mm/hour.
Serum β2
-microglobulin - 14,240.0 ng/mL, LDH - 180 U/l.
Considering the anemic syndrome and bone pain,
immunofixation of pathological serum proteins was
done: M protein was detected, free kappa was
detected 294.33 mg/l.
Test Name
Result
Unit(s)
Biological
reference
interval
Total Protein (Biueret)
7.5
gdL
6.4-8.2
Albumin (Gel Hecfophoresis)
2.72
S/dL
3.57-5.42
Alpha 1 Globutin {Gel
Ebcnrophoresis)
0.14
S/dL
0.19-0.40
Alpha 2 Globutin
0.37
g/dL
0.45-0.96
Beta Globutin
0.45
S/dL
0.30-0.59
Gamma Globulin
3.83
g/dL
0.71-1.54
AlbuminlGlobulin Ratio
0.57
Ratio
1.0-2.2
'M" Band
Present
-
Absent
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According to PET-CT data: metabolic active destructive
foci in all bone structures - changes similar to myeloma?
Pleurisy on both sides. Pericarditis.
In the myelogram dated July 25, 2023: The bone
marrow punctate is medium cellular. Hematological
cells - 100 cells are rare, mostly non-hematological cells
- atypical cells are found.
According to MRI: signs of diffuse damage to the bone
marrow of the skeleton. Hepatosplenomegaly.
Bilateral hydrothorax. Anasarka.
According to trephine biopsy data during microscopic
examination: conclusion: histological picture of plasma
cell dyscrasia.
According to FISH data from 11/21/23:
1. 13q deletion (locus 13q14) not detected
2. Deletion of the TP53 gene (kjre 17p13.1) was not
detected.
3. Translocation t(11;14), leading to the formation of a
fusion signal of the IGH::CCTV1 gene. Not found.
4. Translocation t(4;14), leading to the formation of a
fusion signal of the IGH: FGFR3 gene, was not detected.
Thus, the main diagnosis was established: Multiple
myeloma with Kappa light chain secretion. Diffuse-
focal form. Stage IIIA (according to B. Durie, S.
Salmon). ISS III. R-ISS II.
Related: Q96.9 Turner syndrome, unspecified. I89.0
Lymphoedema, not elsewhere classified.
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Complication: Diffuse damage to the skeletal bones.
Hepatosplenomegaly. Anasarka. Conducted No. 3 VRD:
From 09.12.23 to 11.23.23 3 courses of PCT "VRD"
(Bortezomib 1.0 mg/m2, Lenalidomide 25 mg/day,
Dexamethasone), Hemotransfusion 3p mark. er. wt.
No. 5.
After the 3rd course of treatment, CR was achieved,
maintenance
therapy
was
prescribed
with
lenalidomide 25 mg orally, but after three months the
disease relapsed, treatment with Daratumumab 16
mg/kg + Pomalide 4 mg + dexamethasone was started.
After two courses, partial remission was achieved.
Discussion: There are no cases of multiple myeloma
with Shereshevsky-Turner syndrome described in the
literature. In our case, the patient was not found to
have pathogenetic mutations that play a role in the
development of multiple myeloma. According to the
authors Smith L, Barlogie B, Alexanian R.Smith L, et al.
biclonal tumors often showed atypical myeloma
protein changes with chemotherapy, suggesting that
one clone was reduced while the other remained
unchanged. These data suggest a genetic basis for the
resistance of low-RNA tumors to chemotherapy,
possibly accounting for early relapse. Based on the
therapy performed, one can judge the effectiveness of
PCT according to the VRD protocol in the first line in the
treatment of multiple myeloma with combined
congenital mutations, but early relapse of the disease
requires
polychemotherapy
with
monoclonal
antibodies.
CONCLUSION
Thus, we can conclude that patients with multiple
myeloma with combined congenital mutations should
be classified as a high-risk group despite the absence of
high-risk cytogenetic abnormalities by FISH. MM with
biclonal proteins should be considered a high-risk
group, although the R-ISS classification does not assess
biclonality.
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