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МЕДИЦИНСКИЕ НАУКИ
RARE CASE OF THE CLINICAL COMBINATION OF TWO
NOSOLOGICAL FORMS OF CHROMOSOMAL PATHOLOGY 1 2
Hasanova A-Т. , Sultanova N-Н. Email: [email protected]
1Hasanova Aytakin Tair - PhD in biology, АззаЫ^в Professor, BIOLOGY AND GENETICS DEPARTMENT; 2Sultanova Naila Hasan gizi - Doctor of medical sciences, Professor, INTERNAL DISEASES DEPARTMENT, II DEPARTMENT OF CHILDREN'S DISEASES, АZERBAIJAN MEDICAL UNIVERSITY, BAKU, REPUBLIC OF AZERBAIJAN
Abstract: the text presents a rare case of the clinical combination of two nosological forms of chromosomal pathology in a patient. Down syndrome is characterized by multiple congenital malformations, including changes in the brain and facial skull, and developmental disorders of the musculoskeletal and cardiovascular systems. Congenital developmental abnormalities are also possible with trisomy on the X chromosome. The case of combined chromosomal pathology in a child A. indicates the importance of monitoring of the fetus conditions in the first and second trimesters of pregnancy for the timely detection of fetal malformations and, if necessary, invasive prenatal diagnosis of chromosomal pathology in a specified period to the further decision on prolongation or interruption of a pregnancy with an abnormal fetus.
Keywords: down syndrome, trisomy X, malformations, chromosomal syndromes.
РЕДКИЙ СЛУЧАЙ КЛИНИЧЕСКОЙ КОМБИНАЦИИ ДВУХ НОЗОЛОГИЧЕСКИХ ФОРМ ХРОМОСОМНОЙ ПАТОЛОГИИ Гасанова А.Т.1, Султанова Н.Х.2
1Гасанова Айтакин Таир - кандидат биологических наук, доцент, кафедра биологии и генетики; 2Султанова Наиля Хасан кызы - доктор медицинских наук, профессор, кафедра внутренних болезней, II-й лечебно-профилактический факультет, Азербайджанский медицинский университет, г. Баку, Азербайджанская Республика
Аннотация: в данной статье представлен редкий случай клинической комбинации двух нозологических форм хромосомной патологии у пациента. Синдром Дауна характеризуется несколькими врожденными аномалиями, включая изменения, как в мозговой, так и в лицевой части черепа, а также дефекты развития опорно-двигательной и сердечно-сосудистой систем. Врожденные девиации развития могут также сопровождаться трисомией-X хромосом. Данный случай врожденной комбинированной хромосомной патологии, отмеченный у ребенка А., указывает на важность своевременного контроля условий развития зародыша внутриутробно в первые и вторые триместры беременности, для своевременной диагностики эмбриональных и фетальных уродств, при необходимости, установления предродового диагноза хромосомной патологии в установленный период, а также прерывания беременности при наличии патологии зародыша. Ключевые слова: синдром Дауна, трисомия-Х, уродства, хромосомные синдромы.
УДК: 575, 14.00.09
INTRODUCTION
Aneuploidy is the second most important category of chromosome mutations relating to abnormal chromosome number. Trisomy 21 and numerical sex chromosome anomalies are common chromosomal disorders, with a birth incidence of 1:700 to 1:2,500 respectively [9, p. 24-32.].
The chances of two chromosomal anomalies occurring in a single conceptus are a rare event and the reported incidence varies from 0.21% to 2.8% in spontaneous miscarriages subjected to cytogenetic study [6, p. 73-77].
Nonetheless, the incidences might be more than the expected occurrence, if multiplied by the individual frequencies of each aneuploidy [7, p. 351-39].
However, the underlying mechanism involved in the formation of double aneuploidy (DA) is not well understood. Parental origin is studied only in a small number of cases and both non disjunctions occurring in a single parent is an extremely rare event. Because of the rarity and for an addition to the existing literature, we present a case of double aneuploidy in a clinically suspected case of Down syndrome.
Chromosomal pathology makes a significant contribution to perinatal morbidity and mortality. Only few options of numerical chromosome abnormalities in children are compatible with postnatal development and lead to chromosomal diseases.
The big interest of the clinical case description of combined chromosomal pathologies -Down syndrome and trisomy on the X chromosome in patient A is attractable.
CASE REPORT
A proband is a girl, which was born from the first pregnancy of a 17-year-old mother who was not registered for a pregnancy up to 28 weeks. During registering of a pregnant woman, water deficiency, chronic fetoplacental insufficiency, chronic fetal hypoxia, proteinuria, and trichomoniasis were found. An ultrasound study, first conducted at 32-33 weeks, revealed a syndrome of delayed fetal development, valgus deformity of both legs, pyeloectasia, megaureter, impaired uteroplacental blood flow. At 36 weeks planned operative delivery was carried out, the girl's weight at birth was 1,360, height - 39 cm, head circumference - 29 cm, breast circumference - 24 cm. The state at birth was heavy, crepitating wheezes were detected in the lungs. After one and half hours after the birth because of an increase in respiratory failure patient A. was transferred to the artificial respiration.
On clinical examination of a child were being observed craniofacial dysmorphism (hydrocephalic form of the skull, hypertelorism of the eyes, low-lying deformed auricles, gothic palate), problems of development of the musculoskeletal system (bilateral club foot), and limitation of the hip joints, reduction soft tissue turgor. The skin is icteric, the subcutaneous fat layer is underdeveloped.
From the 11th day of life, patient A. had a rough systolic murmur at the second-third intercostal space with irradiation to the back, sonorous, rhythmic heart sounds. (Fig. 1).In the lungs, breathing was detectable in all fields, the borders of the heart were enlarged, crepitating rales were heard. On the 28th day of life, according to echocardiography, there is a negative trend with an increase of left heart compartments. Rerfer to ECG test at the same age, sinus rhythm, severe tachycardia, hypertrophy of the right atrium were detected, and data for ischemia, a violation of repolarization along the anterior, septal and lower walls of the heart, were also being observed. Specified diagnosis of the girl: congenital heart disease, ventricular septal defect, open arterial duct, aneurysm of interatrial septum is obviously.
Fig. 1. Clinical features of the proband
At 1 month, in patient A., an ultrasound examination of the urinary system revealed border pyeloectasia on the left, and no ecopathology was detected in the abdominal organs. As a multispiral computed tomography of the chest was carried out, a sharp expansion of the cardiac shadow, bronchopulmonary dysplasia was detected. According to the results of the multispiral computed tomography of the brain, we diagnosed hypoxic-ischemic brain lesion, borderline internal hydrocephalus, moderate external hydrocephalus, a congenital anomaly of the cerebellar vermis development - Dandy-Walker malformation.
The cytogenetic conclusion obtained by standard karyotyping with differential staining of chromosomes is 48, XXX, +21, which corresponds to the presence of two additional chromosomes — the X chromosome and the autosome 21. Thus, the proband simultaneously diagnoses two nosological forms of chromosomal pathology - Down syndrome and trisomy on the X chromosome (Fig. 2).
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Fig.. 2. Karyotype showing both trisomyXand trisomy 21
With an increase in cardiac decompensation, there appeared insufficiency of blood circulation of the II B grade, high pulmonary hypertension, as well as severe bilateral pneumonia and respiratory failure of the III grade. At 1 month 14 days, patient A. had a cardiac arrest, resuscitation did not reverse the condition . According to the literature, 60% of children with Down syndrome die before the age of 3 months, only 10% live to a year, while the main cause of death is cardiac impairment and respiratory arrest.
DISCUSSION
According to literary sources, Down syndrome is characterized by multiple congenital malformations, including changes in the brain and facial skull, malformations of the musculoskeletal, cardiovascular systems, that are obviously. When trisomy on the X chromosome is also possible manifestation of congenital developmental abnormalities. The literature describes cases of a combination of two chromosomal abnormalities in one patient. In the case of the patient A., the main developmental abnormalities are associated with more severe malformations characteristic of Down syndrome.
The patient with a karyotype 48, XXX, +21, who had an intrauterine growth retardation, a change in the shape and size of the skull, an inter-ventricular septum defect, a pulmonary stenosis and a clubfoot of the left leg, that was being described by H. Pachajoa [2013]. Thus the phenotype of the patient, as well as in the case of patient A., was determined by the developmental anomalies most often described in Down syndrome.
Double trisomies are rarely seen among live births as most of the cases are inevitably lethal [6, p. 73-77]. Trisomy- 21 and triple- X in the same individual has been reported earlier [Balwan et al. 2008; Devlin and Morrison 2004; Guzel et al. 2009; Kovaleva and Mutton 2005] and phenotypic features of classical Down syndrome were only seen. However, strabismus, periorbital swelling, scanty eyebrows and microganthia observed in the present case have not been observed in earlier reports. Molecular research though carried out in a small number has shown that they are either derived from a single parent or have different parental origin [6, p. 73-77].
In the present study, molecular characterization has shown maternal origin of double aneuploidy with origin of trisomy 21 at meiosis- II and trisomy X at meiosis-I. Though the origin of meiotic error is not known precisely, several factors like age [Diego-Alvarez et al. 2006; Li et al. 2005; Baird and Sadovnick 1988], nutritional (B12/Folate deficiency with hyperhomocystenemia) and /or polymorphism in the gene regulating B12/Folate pathways have shown to be associated with an increased risk of meiotic error [James et al. 1999; Sheth andSheth 2003]. However, in the present case, the age factor is ruled out as maternal age was 26 years at the time of the child's birth. Further study for the common polymorphism in MTHFR gene (677CT or TT) was also normal with low vitamin B-12 in father and normal B-12 status in the mother. Since both non-dysjunction occurred in mother, low vitamin B12 in the father is unlikely to have any role in the present case. This again shows that the cause of meiotic error was either due to abnormal function, due to mutation or regulatory anomaly of unknown genes involved in the meiotic error or genetic predisposition in some families for the double aneuploidy [4. p.958-966]. Prognosis for patients with trisomic miscarriage is favorable. However, the risk of trisomic pregnancies with advanced maternal age is higher [18, p. 465-483.].
Also, patients with an euploid miscarriage have a poor prognosis. This suggests that an alternative cause of miscarriage may exist, such as variants in proteins affecting DNA methylation or meiotic segregation [15, p. 1245-1254.], gonadal mosaicism for a chromosome abnormality or balanced translocations [17, p. 367-373]. In the present case, pregnancy loss in first trimester was difficult to ascertain as no information about the fetal loss was available, and recurrence risk would be difficult to ascertain to the family in presence of normal chromosomal status in both parents. It is likely that some other mechanism of independent non-disjunction might be playing a role in such cases and further studies are needed to elucidate the molecular events for double aneuploidy. Nonetheless, it would be appropriate to advise the family for prenatal diagnosis in subsequent pregnancies.
The case of combined chromosomal pathology in a child A. indicates the importance of monitoring of the fetus conditions in the first and second trimesters of pregnancy for the timely detection of fetal malformations and, if necessary, invasive prenatal diagnosis of chromosomal pathology in a specified period to the further decision on prolongation or interruption of a pregnancy with an abnormal fetus.
References / Список литературы
1. Bochkova V.P., Ginter E.K., Puzyrev V.P. Hereditary diseases. National leadership / ed. M.: GEOTAR-Media, 2012. 936 p.
2. Baird P.A., Sadovnick A.D., 1988. Maternal age-specific rates for Down syndrome: Changes over time. Am J Med Genet, 29 (4): Р. 917-927.
3. Balwan W.K., Kumar P., Raina T.R., Gupta S., 2008. Double trisomy with 48, XXX+21 karyotype in a Down's syndrome child from Jammu and Kashmir. Ind J Genet. 87(3): Р. 257-259.
4. Diego-Alvarez D., Ramos-Corrales C., Garcia-Hoyos M., Bustamante-Aragones. et al. 2006. Double trisomy in spontaneous miscarriages: Cytogenetic and molecular approach. Human Reproduction, 21 (4): Р. 958-966.
5. Devlin L., Morrison P.J., 2004. Accuracy of the clinical diagnosis of Down's syndrome. Ulster Med J, 73(1): Р. 4-12.
6. Guzel A.I., Demirhan O., Pazarbasi A., Ozgunen F.T. et al. 2009. Detection of parental origin and cell stage errors of a double non-disjunction in a fetus by QF-PCR. Genet Test Mol Biomarkers. 13 (1): Р. 73-77.
7. Hook E.B., 1992. Chromosome abnormalities: Prevalence risk and recurrence. In: D.J.H. Brock, C.H. Rodeck, M.A. Ferguson-Smith (Eds.): Prenatal Diagnosis and Screening. Edinburgh: Chirchill-Livingston. Р. 351-39.
8. James S.J., Pogribna M., Pogribny I..P, Melynk S. et al., 1999. Abnormal folate metabolism and mutation in the MTHFR gene may be maternal risk factors for Down syndrome. Am J Clin Nutr, 70: Р. 495-550.
9. Kovaleva N.V., Mutton D.E., 2005. Epidemiology of double aneuploidies involving chromosome 21 and the sex chromosomes. Am J Med Genet A, 134A(1): Р. 24-32.
10. Kozlova S I., Demikova N.S. Inherited syndromes and medical genetic counseling. M.: KMK, 2007. 448 p.
11. Li QY, Tsukishiro S., Nakagawa C., Tanemura M. et al., 2005. Parental origin and cell stage of non-disjunction of double trisomy in spontaneous abortion. Congenit Anom (Kyoto). 45: Р. 21-25.
12. Lorda-Sanchez I., Diego-Alvarez D., Ayuso C., de Alba MR et al., 2005. Trisomy 2 due to a 3:1 segregation in an abortion studied by QF-PCR and CGH. Prenat Diagn, 25: Р. 934-938.
13. Old J.M., Ludlam C.A., 1991. Antenatal diagnosis. Baillieres Clin Hematology, 4: Р. 391-428.
14. Pachajoa H. Double aneuploidy (trisomy X, trisomy 18) in a newborn with trisomy 18 phenotype// Arch Argent Pediatr, 2013. № 111 (4). Р. 101-104.
15. Robinson W.P., McFadden D.E., Stephenson M.D.2001. The origin of abnormalities in recurrent aneuploidy/ polyploidy. Am J Hum Genet, 69: Р. 1245-1254.
16. Sheth J.J., Sheth F.J. 2003. Gene polymorphism and folate metabolism: A maternal risk factor for Down syndrome.Ind Pediatr, 40(2): Р. 115-123.
17. Sugiura-Ogasawara M., Ozaki Y., Sato T., Suzumori N. et al. 2004. Poor prognosis of recurrent aborters with either maternal or paternal reciprocal translocations. Fertil Steril. 81: Р. 367-373.
18. Warburton D., Kline J., Stein Z., Hutzler M. et al. 1987. Does the karyotype of a spontaneous abortion predict the karyotype of a subsequent abortion? Evidence from 273 women with two karyotyped spontaneous abortions. Am J Hum Genet, 41: Р. 465-483.
19. Yuzhakova A. G. A rare case of Down syndrome with X-chromosome disomy / [et al.] // Medical genetics, 2015. № 4. P. 49-50.
ВЛИЯНИЕ КАДМИЯ НА БИОХИМИЧЕСКИЕ ПРОЦЕССЫ В ОРГАНИЗМЕ В УСЛОВИЯХ ЭКСПЕРИМЕНТАЛЬНОГО
ГИПОТИРЕОЗА Гулиева С.В.1, Гараев Г.Ш.2, Халилов В.Г.3, Раджабова Ф.О.4 Email: [email protected]
'Гулиева Севда Вагиф кызы - кандидат биологических наук, доцент, заведующий отделом,
отдел биохимии, Научно-исследовательский центр, Азербайджанский медицинский университет; 2Гараев Галиб Шалон оглу - заслуженный деятель Азербайджана, академик медико-технических наук, доктор медицинских наук, профессор; 3Халилов Видади Гейдар оглу - кандидат биологических наук, доцент, заведующий отделом,
отдел морфологии и гистологии; 4Раджабова Фатма Орудж кызы - кандидат биологических наук, доцент, Научно-исследовательский центр, Азербайджанский медицинский университет, г. Баку, Азербайджанская Республика
Аннотация: в работе приведены результаты биохимических показателей печени, состояния перекисного окисления липидов (ПОЛ) и антиоксидантной защиты (АОЗ) при сочетанном влиянии гипотиреоза и кадмиевой интоксикации. Все экспериментальные исследования проведены в соответствии с этическими требованиями к работе с лабораторными животными. Установлено, что кадмиевая интоксикация изменяет состояние ПОЛ, увеличивает содержание токсических продуктов и нарушает регуляторную функцию ферментов печени при сочетанном действии гипотиреоза и солей тяжелого металла.
Ключевые слова: гипотиреоз, кадмиевая интоксикация, перкисное окисление липидов, токсические продукты.
THE EFFECT OF CADMIUM ON BIOCHEMICAL PROCESSES IN THE BODY UNDER CONDITIONS OF EXPERIMENTAL HYPOTHYROIDISM Guliyeva S.V.1, Garayev G.Sh.2, Halilov V.H.3, Radjabova F.O.4
'Guliyeva Sevda Vaqif - PhD in Biological Sc., Associate Professor, Department Head, DEPARTAMENT OF BIOCHEMIST, RESEARCH CENTER;
2Garayev Galib Shalon - Honorable Worker of Azerbaijan, Academician of Medical and Technical
Sc., Doctor of Medicine, Professor; Khalilov Vidai Heydar - PhD in Biological Sc., Associate Professor, Department Head, DEPARTMENT OF MORPHOLOGY AND HISTOLOGY; 4Radjabova Fatma Orudj - PhD in Biological Sc., Associate Professor, RESEARCH CENTER, AZERBAIJAN MEDICAL UNIVERSITY, BAKU, AZERBAIJAN REPUBLIC
Abstract: the work presents the results of biochemical parameters of the liver, lipid peroxidation state (POL) and antioxidant protection (AOP) with the combined effect of
