Amenorrea primaria asociada a paciente con cariotipo 45 XX, ROB (13; 14) (q 10; q 10): presentación de un caso / Primary amenorrhea associated with a patient with karyotype 45 XX, ROB (13; 14) (q 10; q 10): case presentation

La función ovárica depende de la expresión de múltiples genes, por lo que las anomalías del cromosoma X y los autosomas revisten gran importancia en la etiología de la insuficiencia ovárica primaria (IOP). Las translocaciones de autosomas en mujeres con IOP son muy raras y solo se han detectado tres casos: dos translocaciones entre los cromosomas 2 y 15 en dos mujeres con cariotipo 46, XX, t (2, 15) (q32.3, q13.3)2; una translocación entre los cromosomas 13 y 14 en una mujer con cariotipo 45, XX, t (13; 14)3; por lo que nuestro caso sería el cuarto reporte de mujeres con translocaciones de autosomas e IOP.

Ovarian function depends on the expression of multiple genes, so Xchromosome abnormalities and autosomes are of great importance in the etiology of primary ovarian insufficiency (IOP). Autosomal translocations in women with IOP are very rare and only three cases have been detected: two translocations between chromosomes 2 and 15 in two women with karyotype 46, XX, t (2, 15) (q32.3, q13.3)2; a translocation between chromosomes 13 and 14 in a woman with karyotype 45, XX, t (13; 14)3 , so our case would be the fourth report of women with autosomal translocations and IOP.

Premature ovarian failure: a critical condition in the reproductive potential with various genetic causes

Premature ovarian failure [POF] is identified as a heterogeneous disorder leading to amenorrhea and ovarian failure before the age of 40 years. The first known symptom of the disease is having irregular menstrual periods. The phenotype appearance of POF depends significantly on the variations in hormones. Low levels of gonadal hormones [estrogens and inhibins] and increased level of gonadotropins [luteinizing hormone [LH] and Follicle stimulating hormone [FSH]] [hypergonadotropic amenorrhea] are well documented as causes of POF. There is an association between the failure of germ cell development and complete ovarian failure, and consistently decreased number of germ cells is more likely associated with partial ovarian failure resulting in secondary amenorrhea. A literature review on recent findings about POF and its association with genomic alterations in terms of genes and chromosomes. POF is a complex heterogeneous disorder. Some of POF cases are carriers of a single gene mutation inherited in an autosomal or X-linked manner while a number of patients suffer from a chromosome abnormality like Turner syndrome in mosaic form and manifest secondary amenorrhea associated with ovarian dysgenesis. Among many of the known involved genes in POF development, several are prove to be positively associated to the disease development in different populations. While there is a promising association between X chromosome anomalies and specific gene mutations with POF, genome-wide analysis could prove a powerful tool for identifying the most important candidate genes that influence POF manifestation

Deoxyribonucleic acid damage study in primary amenorrhea by comet assay and karyotyping.

AIM: This study aims at evaluating the chromosomal abnormalities and deoxyribonucleic acid (DNA) damage in cases with primary amenorrhea by karyotyping and comet assay. STUDY DESIGN: A total of 30 cases of primary amenorrhea were recruited. Secondary sexual characters were assessed by Tanner staging. Chromosomal analysis was performed by conventional phytohemagglutinin stimulated lymphocyte cell culture technique. Alkaline version of comet assay was used to evaluate DNA damage. RESULTS: The chromosomal pattern of 20 subjects (66.7%) was found to be normal (46,XX). Two subjects had 46,XY pattern and eight subjects had Turner syndrome (45,X or 45,X/46,XX). The comet parameters were found to be increased among subjects with 45,X monosomy, when compared to the rest of the study group and also in subjects with Tanner stage 1 when compared to stage 2. CONCLUSION: Comet assay revealed increased DNA damage in cases with 45,X monosomy, compared with subjects with 46,XX and 46,XY karyotype, which correlated with clinical features.

A case of primary amenorrhea with 46+XY genotype from Kashmir Valley.

Primary amenorrhea is one of the common reproductive disorder affecting females. It leads to the absence of menarche in the reproductive age group in females and/or complete absence of reproductive organs. There are many causes which lead to PA, including genetic aberrations which are the leading factors.

Síndrome de Morris / Morris Syndrome

Introducción: el síndrome de resistencia completa a los andrógenos, feminización testicular o síndrome de Morris, puede presentarse en uno de cada 20 000 a 64 000 recién nacidos varones. Objetivo: presentar un caso con genotipo masculino y fenotipo femenino dado por desarrollo mamario, con genitales externos femeninos con hipoplasia de los labios mayores y menores y la vagina muy corta que termina en un fondo de saco ciego. Métodos: se valora en la consulta a una paciente adolescente de 19 años de edad con amenorrea primaria y contacto sexual insatisfactorio (imposibilidad de penetración). Resultados: se comprueba al examen vagina rudimentaria de unos dos centímetros y escaso desarrollo de genitales externos. En los exámenes complementarios se comprueban cifras de testosterona y LH aumentadas, así como el estradiol disminuido y un cariotipo 46 XY por lo que se sospecha síndrome de Morris y se planifica intervención quirúrgica combinada en un tiempo (vaginal y abdominal) donde se realiza anexectomía total derecha por video laparoscopia y reconstrucción de vagina por técnica de Williams. Posoperatorio satisfactorio y seguimiento ulterior por consulta donde se comprueba vagina funcional y estabilidad emocional de la paciente. Conclusiones: el estudio anatomo-patológico comprueba la existencia de ovario y testículo en la muestra quirúrgica lo que confirma el diagnóstico de síndrome de Morris o de resistencia completa a los andrógenos

Introduction:the syndrome of complete androgen resistance, testicular feminization or Morris syndrome may occur in one in 20 000 to 64 000 of male newborns. Objective: to present a case with male genotype and female phenotype given by breast development, female external genitalia with hypoplasia of the labia and very short vagina ending in a blind pouch Methods: a 19 year- old female patient is assisted in consultation due primary amenorrhea and unsatisfactory sexual contact (impossibility of penetration). Results: at examination, we found a rudimentary vagina of about two inches and underdeveloped external genitalia. The exams confirmed increased LH and testosterone levels and decreased estradiol. It is also found a 46 XY karyotype, so Morris syndrome is suspected. Combined surgery is planned for the vagina and abdomen. Total videolaparoscopy right adnexectomy and vaginal reconstruction by technique of Williams are performed. We had satisfactory postoperative and subsequent follow-up consultation where functional vagina and emotional stability of the patient were checked. Conclusions: the pathological study verifies the existence of ovary and testis in the surgical specimen confirming the diagnosis of Morris syndrome or complete androgen resistance

Chromosomal abnormalities and hormonal disorders of primary amenorrhea patients in Egypt.

Background: Primary amenorrhea is defined as the absence of menstruation and secondary sexual characteristics in phenotypic women aged 14 years or older. Hormonal disorders are main causes of primary amenorrhea. Common hormonal cause of primary amenorrhea includes pituitary dysfunction and absent ovarian function. The aim of this study was to estimate the incidence and types of chromosomal abnormalities in patients with primary amenorrhea in Egypt. Materials and Methods: Chromosomal analysis and hormonal assay were carried out on 223 patients with primary amenorrhea that were referred from different parts of Egypt to Cytogenetic laboratory of Genetic Unit, Children Hospital Mansoura University, from July 2008 to December 2010. FISH technique was carried out in some of cases to more evaluation. Results: The frequency of chromosomal abnormalities was 46 (20.63%) in primary amenorrhea patients. The chromosomal abnormalities can be classified into four main types. (1) The numerical abnormalities of the X chromosome were detected in 23 (50 %). (2) Structural abnormalities of the X chromosome were detected in 11 (23.91%). (3) Mosaicism of X chromosome was found in 10 (21.74%). (4) Male karyotype 46, XY was presented in 2 (4.35%). Conclusion: The present study showed that karyotype and FISH are necessary to detect the causes of primary amenorrhea. This study also revealed the incidence of chromosomal abnormalities in women with primary amenorrhea in Egypt is similar to that reported in previous literatures.

Amenorréia e anormalidades do cromossomo X / Amenorrhea and X chromosome abnormalities

OBJETIVO: correlacionar as manifestações clínicas de pacientes com amenorréia e anormalidades do cromossomo X. MÉTODOS: realizou-se uma análise retrospectiva dos achados clínicos e laboratoriais das pacientes com amenorréia e anormalidades do cromossomo X, atendidas entre janeiro de 1975 e novembro de 2007. Suas medidas antropométricas foram avaliadas através de tabelas de crescimento padrão, sendo que, quando presentes, dismorfias menores e maiores foram anotadas. O estudo dos cromossomos foi realizado através do cariótipo com bandamento GTG. RESULTADOS: do total de 141 pacientes com amenorréia, 16 por cento apresentavam anormalidades numéricas e 13 por cento estruturais do cromossomo X. Destas pacientes com anormalidade do X (n=41), 35 possuíam descrição clínica completa. Todas elas apresentavam hipogonadismo hipergonadotrófico. Amenorréia primária foi observada em 24 pacientes, das quais 91,7 por cento com fenótipo de síndrome de Turner. Com exceção de um caso com deleção Xq22-q28, todas as demais pacientes com este fenótipo apresentavam alterações envolvendo Xp (uma com uma linhagem 46,XY associada). Os dois casos restantes com apenas amenorréia primária possuíam deleções proximais de Xq. Entre as 11 pacientes com amenorréia secundária, 54,5 por cento apresentavam fenótipo de Turner (todas com monossomia do X isolada ou em mosaico). Entre aquelas com fenótipo de falência ovariana isolada observaram-se somente deleções Xq e trissomia do X. CONCLUSÕES: a análise cromossômica deve sempre ser realizada em mulheres com falência ovariana de causa não conhecida, mesmo na ausência de achados dismórficos. Esta também é de extrema importância em pacientes sindrômicas, pois, além de confirmar o diagnóstico, é capaz de identificar pacientes em risco, como nos casos com uma linhagem 46,XY.

PURPOSE: to correlate the clinical manifestations of patients with amenorrhea and X chromosome abnormalities. METHODS: a retrospective analysis of the clinical and laboratorial findings of patients with amenorrhea and abnormalities of X chromosome, attended between January 1975 and November 2007 was performed. Their anthropometric measures were evaluated through standard growth tables, and, when present, minor and major anomalies were noted. The chromosomal study was performed through the GTG banded karyotype. RESULTS: from the total of 141 patients with amenorrhea, 16 percent presented numerical and 13 percent structural abnormalities of X chromosome. From these patients with X chromosome abnormalities (n=41), 35 had a complete clinical description. All presented hypergonadotrophic hypogonadism. Primary amenorrhea was observed in 24 patients, 91.7 percent of them with a Turner syndrome phenotype. Despite a case with Xq22-q28 deletion, all patients with this phenotype presented alterations involving Xp (one case with an additional cell lineage 46,XY). The two remaining patients with only primary amenorrhea had proximal deletions of Xq. Among the 11 patients with secondary amenorrhea, 54.5 percent presented a Turner phenotype (all with isolated or mosaic X chromosome monosomy). Patients with phenotype of isolated ovarian failure had only Xq deletions and X trisomy. CONCLUSIONS: the cytogenetic analysis must always be performed in women with ovarian failure of unknown cause, even in the absence of clinical dysmorphic features. This analysis is also extremely relevant in syndromic patients, because it can either confirm the diagnosis or identify patients in risk, like the cases involving a 46,XY lineage.

Genotype-phenotype correlation in 46, XY females

XY females are phenotypically females, but with XY karyotype. Our aim was to correlate the genotype with phenotype in cytogenetically confirmed 46 XY females. Retrospective study of a thirty year data Division of Human Genetics, St. John's Medical College, Bangalore, India Six hundred and twenty consecutively referred individuals with primary amenorrhea Phenotype features and XY female characteristics Fifty-seven [9.2%] cases were identified with 46, XY karyotype. Primary features: Uterus was absent in 33/47 [70.2%] cases and gonads absent in 18/34 [52.9%]. Complete female external genitalia was observed in 36/48 [75%], ambiguous genitalia with clitoromegaly in 12/57 [21.1%], normal vagina in 13/48 [27.1%], blind in 27 [56.3%] and absent in 8 [16.7%] cases. In secondary features, normal breast was seen in 23/54 [42.6%], hypoplastic in 16 [29.6%] and absent in 15 [27.8%] cases. Axillary and pubic hair was normal in 6 [11.1%] and poorly developed in 48 [88.9%]. Twelve [85.8%] were born to consanguineous parents and 8 had first cousin relationship [66.7%]. The highly significant features associated with consanguinity were normal axillary hair, ovotestis, absent vagina and significant features were hypoplastic / normal pubic hair, absent gonads and clitoromegaly. The observed differences in the percentage calculation were because of the overlapping in features as well as the available information in the records. Genotype and phenotype correlation revealed that in primary features, absence of mullerian derivatives and gonads were important whereas in secondary features, axillary and pubic hair was poorly developed

Primary amenorrhea varied etiology

Investigation of primary amenorrhea is usually initiated by the age of 14 years if there is delayed puberty absent secondary sexual characteristics and absent menses, or no menstruation within 4 years of the onset of adrenarche and thelarche. We established diagnosis in our 3 cases on the basis of chromosomal analysis, hormonal analysis, diagnostic laparoscopy, and histopathological examination of the samples biopsied. We identified 3 varied etiologies

Ovarian dysgenesis with balanced autosomal translocation.

Autosomal translocations are rare in the patients with ovarian dysgenesis. An 18-year-old female who presented with primary amenorrhoea had hypergonadotropic hypogonadism and streak ovaries with hypoplastic uterus. Karyotype analysis revealed a balanced autosomal translocation involving chromosomes 1 and 11. The probable role of autosomal translocations in ovarian dysgenesis has been discussed.

Estudo citogenético em 80 casos de amenorréia secundária / Cytogenetic study in 80 cases of secondary amenorrhea

OBJETIVO: investigar as alteraçöes citogenéticas, em sangue periférico, em um grupo de mulheres com queixa de amenorréia secundária. AMOSTRA: 80 mulheres atendidas no setor de ginecologia do CAISM, no período de abril de 1990 a março de 1997. DESENHO: idade inferior a 40 anos e queixa principal de amenorréia por período mínimo de 3 ciclos. Os parâmetros estudados compreenderam as dosagens de FSH e LH, realizadas através da técnica de radioimunoensaio, o estudo cromossômico em sangue periférico, realizado em bandas GTG e as quantificaçöes da cromatina X em sedimento urinário. RESULTADOS: a análise citogenética revelou 73 casos com cariótipo normal 46,XX e valores de cromatina X compatíveis com a normalidade, inclusive em 6 casos com estigmas turnerianois. As alteraçöes observadas compreenderam 4 casos de aneuploidias puras, (47,XXX e 45,X), 2 casos de mosaicismo (45,X/46,XX e 45,X/46,X,isoXq) e um caso de deleçäo em braço longo (46,X,delXq(p22q22.1), todos com valores de cromatina X compatíveis com os resultados de cariótipo. As dosagens de LH e FSH permitiram a divisäo da amostra nos subgrupos normo e hipergonadotróficos, com maior incidência deste último e distribuiçäo aproximadamente eqüitativa de alteraçöes citogenéticas nos mesmos. CONCLUSÄO: no grupo estudado, 9 por cento das mulheres apresentaram amenorréia secundária de origem citogenética. Nestes casos, a instalaçäo do quadro clínico ocorreu com idade inferior a 30 anos, em mulheres com sinais clínicos específicos, como baixa ou alta estatura e graus variados de hipodesenvolvimento dos caracteres sexuais secundários. Os valores de cromatina sexual, embora compatíveis com os resultados de cariótipo, mostratam-se ineficazes na detecçäo de mosaicismo e/ou alteraçöes estruturais do cromossomo X. Os autores salientam a necessidade de investigaçäo citogenética de sangue periférico nas mulheres com manifestaçäo de amenorréia secundária com idade inferior a 30 anos e, nos casos de infertilidade por falência ovariana de origem desconhecida e cariótipo 46,XX, a investigaçäo de mosaicismo gonadal.

Cytogenetic study of primary amenorrhoea.

A study of chromosomal pattern was done in 60 cases of primary amenorrhoea of different age groups to determine the incidences of chromosomal abnormalities in them and to detect those cases of classical 45, X Turner's syndrome and Turner mosaics that do not bear the Turner stigmata. Buccal smears were examined for sex chromatin followed by karyotype using leucocyte culture method. Majority (63.3%) of cases were found chromosomally incompetent of which the major abnormality was 45, X/46, XX mosaicism (33.3%) followed by 45, X Turner's syndrome (26.6%). But only 43.7% of these Turner's syndrome had classical Turner stigmata. Two cases of complete testicular feminisation syndrome with male genotype (46,XY) and inguinal testis were also detected.

Falência ovariana precoce: relato de 23 casos / Premature ovarian failure: report of 23 cases

A falência ovariana precoce é caracterizada por uma amenorréia secundária hipergonadotrófica, que ocorre antes dos 40 anos de idade. Neste estudo foram avaliadas retrospectivamente 23 pacientes admitidas no Ambulatório de Menopausa do DTG-CAISM-UNICAMP no período de janeiro de 1986 a julho de 1990. A idade média das pacientes quando se instalou o quadro de amenorréia foi de 31,17 anos (+ 6,20), variando entre 16 e 39 anos, e o tempo médio de amenorréia foi de 32,3 meses (+ 4,33). Quanto aos dados clínicos, 66 por cento das pacientes apresentavam fertilidade prévia e 69,5 por cento apresentavam sintomatologia de ondas de calor. As gonadotrofinas séricas apresentavam-se elevadas em todas as pacientes. Quanto aos hormônios tireoidianos, houve apenas um caso de hipotireoidismo primário. O estudo do cariótipo revelou um caso de síndrome do triplo X (47XX) e uma isocromossomia do braço longo do X (46Xi - Xq). A biópsia ovariana näo evidenciou a presença de folículos em nenhum caso. Os autores comentam alguns dados relevantes de acordo com a revisäo da literatura e enfatizam a importância de se realizar um diagnóstico preciso nesses casos.

Estudo retrospectivo de 227 pacientes com amenorreia primaria / Retrospective study in 227 patients with primary amenohhrea

No periodo compreendido entre 1971 e 1989 foram estudadas 227 pacientes com amenorreia primaria, cujas idades variaram de 18 a 46 anos (media 22,3 anos), com o objetivo de avaliar a casuistica dessa entidade em relacao aos fatores etiopatogenicos e analisar as principais caracteristicas clinicas e laboratoriais das pacientes portadoras de malformacoes mullerianas e estados intersexuais. O estudo revelou grande polimorfismo etiopatogenico...

Chromatid association in acrocentric chromosomes of abnormal sexual development (ASD) cases.

Concordant/discordant associations at chromatid level were compared and found significant (P less than 0.05) in females with primary amenorrhea. This probably suggested that the acrocentric association pattern in this group of ASD and infertility did not follow a random segregation in subsequent cell divisions and that the concordant acrocentric chromosomes have regularly established physical connections with one another, held together for several cell cycles. It could only be speculated that the association of acrocentric chromosome anomalies in some females with abnormal sex chromosomes are due to this reason. In the event that chromosome association has a bearing on chromosome aberrations, the non-random pattern of acrocentric association probably would increase the choice for translocation and non disjunction in the somatic cells in females with primary amenorrhea during ontogenesis.

Frequency of acrocentric association in abnormal sexual development in males and females.

A significant difference (P less than 0.05) was observed in a chi 2 comparison of DD, GG and DG-DI associations between male hypogonads and females with primary amenorrhea. This difference increased still further (P less than 0.01) when only DD and GG associations were compared between males and females with abnormal sexual development (ASD). Similarly, when normal males and females were compared for DI, TRI, TETRA, DD vs GG and DG vs GG acrocentric chromosome associations, a significant difference (P less than 0.05) was again observed. The sex difference was also apparent in TRI and TETRA acrocentric associations both in abnormal and normal sexual development males and females. These results suggested that probably sex difference (may be hormonal) influences the number and/or type of acrocentric chromosomes involved in association between males and females with ASD and also between normal males and females.