Ove hurts. An old cliché reborn a propos of a clinical case / Dolores de amor. Un cliché renacido a propósito de un caso clínico

Introduction: The spectrum of sexually motivated behaviors is extremely wide, including behaviors that are not biologically reprductive and hold exclusively ludic functions. We refer to the persistent and recurrent patterns of sexual arousal resulting from the exposure to non-normative sexual stimuli as paraphilias, and they are paradigmatic of the broad heterogeneity of human sexuality. Among these, paraphilic infantilism was first reported in the scientific literature by Tuchman and Lachman in 1964. It is characterized by the presence of sexual arousal or pleasure when playing childhood roles or using objects proper of childhood.Objective: We intend to describe a clinical case, with a focus on the atypical profile of sexual interests and behaviors comprising paraphilic infantilism and sadomasochism phenomena. We also seek to discuss the understanding of these phenomena in the context of the global clinical picture, their nosological framework, and their implication in the psychotherapeutic process.Methodology: In this study, we present the clinical case of a patient observed in the outpatient clinic of the first author. A targeted literature review was carried out through a bibliographic search in the PubMed database and a selection of reference works in the Sexology field. These data provided a basis from which we develop our clinical discussion of the case.Results: This article illustrates the case of a patient referred for psychotherapeutic intervention due to an anxious-depressive syndrome. During follow-up, a cluster of sexual behaviors was observed that involved preferential sexual interest for role-playing as a baby, and practices that involved physical suffering, dominance and submission. Conclusions: Paraphilia is a controversial clinical category...(AU)

Introducción: El espectro de conductas con motivación sexual es muy amplio, abarcando conductas que no son biológicamente reproductivas y que sostienen funciones exclusivamente lúdicas. Se denominan parafilias a los patrones persistentes y recurrentes de excitación sexual resultante de la exposición a estímulos sexuales no normativos, y su existencia resulta paradigmática de la amplia heterogeneidad de la sexualidad humana. Entre ellas, el Infantilismo parafílico fue descrito por primera vez en la literatura científica Tuchman y Lachman en 1964 y se caracteriza por obtener excitación o placer sexual a través de la representación de roles infantiles o del uso de objetos propios de la infancia. Objetivo: Nos proponemos describir un caso clínico, enfocando el perfil atípico de intereses y conductas sexuales que comprenden fenómenos de Infantilismo parafílico y Sadomasoquismo. Pretendemos discutir la comprensión de estos fenómenos en el contexto del cuadro clínico global, su marco nosológico y su implicación en el proceso psicoterapéutico. Metodología: Se relata el caso clínico de una paciente observada en el ámbito de la consulta de la primera autora. Se realiza una revisión no sistemática de la literatura científica a través de una búsqueda bibliográfica en la base de datos Pubmed y de la consulta de obras de referencia en el área de la Sexología. Se procede a la discusión clínica, basada en los datos presentados. Resultados: Este artículo ilustra el caso de una paciente, derivada a intervención psicoterapéutica por síndrome ansioso-depresivo. Durante el acompañamiento, se identificó un patrón de respuesta sexual caracterizado por un interés sexual preferencial en representar el rol de un bebé y prácticas que implicaban sufrimiento físico, dominación y sumisión. Conclusiones: La Parafilia es una entidad clínica controvertida...(AU)

Two Cases with 17-alpha Hydroxylase Deficiency Misdiagnosed as Primary Aldosteronism.

AIM: Lack of CYP17A1 prevents sex steroid biosynthesis, yielding a female phenotype in 46, XY males and sexual infantilism in both sexes; overproduction of 11-deoxycorticosterone (DOC) in the zona fasciculata typically causes mineralocorticoid hypertension. In this study, we report two cases of severe hypokalemia, hyperaldosteronism, and sexual infantilism. CASE PRESENTATION: Case 1 admitted severe hypertension and hypokalemia with female external genitalia with 46, XY. The patient also had right adrenal masses of 35*30 mm diameters. Case 2 was presented with delayed pubertal development with 46, XX genotype. In addition, she had severe hypertension and hypokalemia with nodular surrenal hyperplasia in her abdomen imaging. METHODS: Further hormonal and biochemical results were followed as elevated adrenocorticotropic hormone (ACTH) levels, low serum cortisol, 17 hydroxy progesterone (17 OHP) and dehydroepiandrosterone sulphate (DHESO4) and estradiol (E2) levels in both cases. RESULTS: Genetical analyses confirmed 17 OHP deficiency in both cases. CONCLUSION: The condition of patients with 17 alpha-hydroxylase deficiency may substantially resemble primary hyperaldosteronism and must be considered in patients as primary hypogonadism (and) associated with mineralocorticoid hypertension.

Hypopituitarism in five PROP1 mutation siblings: long-lasting natural course and the effects of growth hormone replacement introduction in middle adulthood.

Twenty years after the first description of combined hypopituitarism (CPHD) caused by PROP1 mutations, the phenotype of affected subjects is still challenging for clinicians. These patients suffer from pituitary hormone deficits ranging from IGHD to panhypopituitarism. ACTH deficiency usually develops later in life. Pituitary size is variable. PROP1 mutation is the most frequent in familial congenital hypopituitarism (CH). Reports on initiation of hormonal replacement including growth hormone (GH) in adults with CH are scarce. We identified 5 adult siblings with CPHD due to PROP1 mutation (301-302delAG), aged 36-51 years (4 females), never treated for hormone deficiencies. They presented with short stature (SD from - 3.7 to - 4.7), infantile sexual characteristic, moderate abdominal obesity and low bone mineral density in 3 of them. Complete hypopituituitarism was confirmed in three siblings, while two remaining demonstrated GH, TSH, FSH and LH deficiencies. Required hormonal replacement including rhGH was initiated in all patients. After several months necessity for hydrocortisone replacement developed in all patients. After 2 years of continual replacement therapy, BMD and body composition (measured by DXA-dual X-ray absorptiometry) improved in all subjects, most prominently in two younger females and the male sibling. Besides rhGH therapy, these three patients have received sex hormones contributing to the favorable effect. The male sibling was diagnosed with brain glioblastoma two years following complete hormonal replacement. This report provides important experience regarding hormonal replacement, particularly rhGH treatment, in adults with long-term untreated CH. Beneficial effect of such therapy are widely acknowledged, yet these subjects could be susceptible to certain risks of hormonal treatment initiated in adulthood. Careful and continual clinical follow-up is thus strongly advised.

17α­hydroxylase/17,20­lyase deficiency in congenital adrenal hyperplasia: A case report.

Congenital adrenal hyperplasia (CAH) is a rare autosomal recessive disorder caused by mutations in the cytochrome P450 family 17 subfamily A member 1 (CYP17A1) gene located on chromosome 10q24.3, which leads to a deficiency in 17α­hydroxylase/17,20­lyase. The disorder is characterized by low blood levels of estrogens, androgens and cortisol, which leads to a compensatory increase in adrenocorticotropic hormone levels that stimulate the production of mineralocorticoid precursors. This subsequently leads to hypertension, hypokalemia, primary amenorrhea and sexual infantilism. Over 90 distinct genetic lesions have been identified in patients with this disorder. The prevalence of common mutation of CYP17A1 gene differs among ethnic groups. Treatment of this disorder involves replacement of glucocorticoids and sex steroids. Estrogen alone is prescribed for patients who are biologically male with 17α­hydroxylase deficiencies that identify as female. However, genetically female patients may receive estrogen and progesterone supplementation. In the present study, a 17­year­old female with 17α­hydroxylase/17,20­lyase deficiency that presented with primary amenorrhea and sexual infantilism and no hypertension, was examined. The karyotype of the patient was 46, XX, and genetic analysis revealed the presence of a compound heterozygous mutation in exons 6 and 8, leading to the complete absence of 17α­hydroxylase/17,20­lyase activity. The patient was treated with prednisolone and ethinyl estradiol. In addition, a summary of the recent literature regarding CAH is presented.

Sexual infantilism in a normal karotypic female related to ovarian agenesis associated with Müllerian agenesis--Case report.

PURPOSE: To describe an unusual case of Müllerian agenesis associated with gonadal agenesis and thus sexual infantilism. MATERIALS AND METHODS: Pelvic magnetic resonance imaging (MRI) and sonography were performed and MRI of the kidneys. Pelvic sonography and serum follicle stimulating hormone (FSH) were also obtained. RESULTS: The only pelvic organ that this 15-year-old girl had was the distal portion of the vaginal canal. The kidneys were normal. CONCLUSIONS: This case suggests that at least in some cases some possible viral damaging process may lead to damage to both the ovaries and the Müllerian system. If there was a problem with the anti-Müllerian hormone (AMH), the kidney may be affected. Furthermore, AMH has nothing to do with the ovaries and a chance association of these two entities though possible, seems less likely than a common factor causing both problems.

Untreated Congenital Adrenal Hyperplasia with 17-alpha Hydroxylase/17,20-Lyase Deficiency Presenting as Massive Adrenocortical Tumor

Congenital adrenal hyperplasia (CAH) with 17alpha-hydroxylase/17,20-lyase deficiency is usually characterized by hypertension and primary amenorrhea, sexual infantilism in women, and pseudohermaphroditism in men. hypertension, and sexual infantilism in women and pseudohermaphroditism in men. In rare cases, a huge adrenal gland tumor can present as a clinical manifestation in untreated CAH. Adrenal cortical adenoma is an even more rare phenotype in CAH with 17alpha-hydroxylase/17,20-lyase deficiency. A 36-year-old female presented with hypertension and abdominal pain caused by a huge adrenal mass. Due to mass size and symptoms, left adrenalectomy was performed. After adrenalectomy, blood pressure remained high. Based on hormonal and genetic evaluation, the patient was diagnosed as CAH with 17alpha-hydroxylase/17,20-lyase deficiency. The possibility of a tumorous change in the adrenal gland due to untreated CAH should be considered. It is important that untreated CAH not be misdiagnosed as primary adrenal tumor as these conditions require different treatments. Adequate suppression of adrenocorticotropic hormone (ACTH) in CAH is also important to treat and to prevent the tumorous changes in the adrenal gland. Herein, we report a case of untreated CAH with 17alpha-hydroxylase/17,20-lyase deficiency presenting with large adrenal cortical adenoma and discuss the progression of adrenal gland hyperplasia due to inappropriate suppression of ACTH secretion.

Estudio preliminar sobre el tratamiento con hormona de crecimiento humana recombinante en el síndrome de Turner / Preliminary study on the recombinant human growth hormone treatment of Turner's syndrome

Introducción: los pacientes con síndrome de Turner presentan una monosomía parcial o total del gonosoma X, disgenesia gonadal, diversos rasgos físicos típicos, baja talla e infantilismo sexual. Objetivo: evaluar el efecto del tratamiento con hormona de crecimiento recombinante sobre la talla en las pacientes con el diagnóstico clínico y cromosómico de síndrome de Turner. Métodos: se realizó un estudio de tipo descriptivo y retrospectivo a pacientes con síndrome de Turner atendidas en consultas externas en el Departamento de Endocrinología Pediátrica del Instituto Nacional de Endocrinología, desde mayo de 2003 hasta mayo de 2004. La muestra estuvo constituida por 19 niñas. Se confeccionaron dos grupos, uno con aquellas pacientes que recibieron tratamiento con hormona de crecimiento recombinante (n= 9) a una dosis de 0,14 UI/kg/día, administrada vía subcutánea entre las 8:30 y 9:30 pm, que se conoció como grupo A. El segundo quedó conformado con las pacientes que no recibieron dicha hormona (n= 10), denominado grupo B. Los datos necesarios para la investigación fueron obtenidos de la revisión de las historias clínicas. Resultados: un incremento de la talla en el grupo A, que inició el estudio con una talla basal media de 131,7 ± 7,5 cm, para alcanzar una talla media, después de un año de tratamiento, de 137,9 ± 7,1 cm, con una velocidad de crecimiento media en ese año de 6,2 ± 2,3 cm/año. La comparación de ambos grupos después de un año de estudio mostró diferencias significativas en la talla media al año (p= 0,0071) y la velocidad de crecimiento media al año (p= 0,0032). Conclusiones: el tratamiento con hormona de crecimiento recombinante durante el primer año resultó efectivo, al acelerar significativamente la velocidad de crecimiento en las niñas con síndrome de Turner. La ganancia de peso corporal resultó adecuada durante el periodo de estudio, pues se logró mantener una valoración nutricional estable sin modificaciones en el canal percentilar. La inducción de la pubertad no cambió el pronóstico de la talla al final del estudio(AU)

Introduction: Turner's syndrome patients present with total or partial monosomy of X gonosome, general disgenesia, several typical physical traits, short height and sexual infantilism. Objective: to evaluate the effect of recombinant human growth hormone-based treatment on the height of patients clinically and chromosomally diagnosed as Turner's syndrome subjects. Methods: a retrospective and descriptive study was conducted in Turner's syndrome patients, who had been seen from May 2003 to May 2004 at the pediatric endocrinology department of the National Institute of Endocrinology. The sample was made up of 19 girls divided into 2 groups. Group A comprised patients who were treated with recombinant human growth hormone (n= 9) at a dose of 0.14 IU/kg/day subcutaneously administered from 8:30 to 9:30 pm. Group B included the patients who did not receive this treatment (n= 10). The required data for the research stemmed from the medical history check-ups. Results: increase of the Group A patients' height, whose mean basal height at the beginning of the study was just 131.7 ± 7.5 cm and after one year of treatment, they reached 137.9 ± 7.1 cm, at a rate of average growth of 6.2 ± 2.3 cm/year. The comparison of both groups after one year showed significant differences in mean height (p= 0.0071) and mean growth a year (p= 0.0032). Conclusions: the treatment of these patients with the recombinant growth hormone during the first year was effective, since it markedly accelerated the rate of growth in girls with Turner's syndrome. The body weight gain proved to be adequate in the study period, because it managed to keep steady nutritional assessment without changes in the percentile canal. Inducement to puberty did not alter the final height prognosis at the end of the study(AU)

Congenital adrenal hyperplasia masquerading as periodic paralysis in an adolescent girl.

Congenital adrenal hyperplasia is an uncommon diagnosis in routine clinical practice. 21-hydroxylase deficiency, which is its most common subtype, may be diagnosed at birth in a female infant by virilisation or by features of salt wasting in both genders. However, other uncommon subtypes of this condition such as 17-alpha-hydroxylase deficiency, 11-beta-hydroxylase deficiency may present much later in adolescence or adulthood. A high index of suspicion is necessary when evaluating children with hypertension, hypokalaemia, metabolic alkalosis or sexual infantilism.

Hypogonadism in a patient with two novel mutations of the luteinizing hormone ß-subunit gene expressed in a compound heterozygous form.

CONTEXT: LH gene mutations are rare; only four mutations have been described. The affected individuals are hypogonadal. PATIENT: We describe the clinical features of a 31-yr-old man who presented with delayed puberty and azoospermia and was found to have hypogonadism associated with an absence of circulating LH. MAIN OUTCOME MEASURES AND RESULTS: The patient had a 12-bp deletion in exon 2 in the LH ß-subunit gene and a mutation of the 5' splice site IVS2+1G→T in the same gene present in a compound heterozygous state. The first mutation predicts a deletion of four leucines of the hydrophobic core of the signal peptide. The second mutation disrupts the splicing of mRNA, generating a gross abnormality in the processing. The patient's heterozygous parents were clinically normal. The phenotype of a 16-yr-old sister of the proband, carrying the same mutations, was characterized by normal pubertal development and oligomenorrhea. CONCLUSION: This report unravels two novel mutations of the LH gene critical for synthesis and activity of the LH molecule. The insight gained from the study is that normal pubertal maturation in women can occur in a state of LH deficiency, whereas LH is essential for maturation of Leydig cells and thus steroidogenesis, puberty, and spermatogenesis in man. These mutations should be considered in girls and boys with selective deficiency of LH.

Adult cystic fibrosis--a rare diagnosis from India.

Cystic fibrosis (CF) is a multisystem disease characterized by chronic pulmonary infection, bronchiectasis, exocrine pancreatic insufficiency and elevated sweat chloride level. It is commonly considered as a pediatric disease. But it is now being diagnosed in increasing number of adults due to increased survival from availability of potent antibiotics, nutritional facility and diagnosis of mild cases which were unrecognized previously. CF is rarely reported from India and its adult presentation is rarer. Our case, a Hindu female from West Bengal, India was diagnosed to have CF at the age of 29 years. She had chronic cough and wheezing since childhood being treated as asthmatic patient. She had poor nutrional status, short stature and sexual infantilism. She had premature cataract. Because of chronic cough and expectoration we performed HRCT scan of thorax which revealed bilateral bronchiectasis. She had bilateral maxillary sinusitis and hypoplastic frontal sinus. Repeated sweat chloride tests revealed high values suggestive of CF. CF should be considered in differential diagnosis of adults with bronchiectasis and chronic sinusitis or child with bronchial asthma. High level of awareness is needed to diagnose CF in India, because of its rarity.

Congenital adrenal hyperplasia masquerading as periodic paralysis in an adolescent girl

Congenital adrenal hyperplasia is an uncommon diagnosis in routine clinical practice. 21-hydroxylase deficiency, which is its most common subtype, may be diagnosed at birth in a female infant by virilisation or by features of salt wasting in both genders. However, other uncommon subtypes of this condition such as 17-alpha-hydroxylase deficiency, 11-beta-hydroxylase deficiency may present much later in adolescence or adulthood. A high index of suspicion is necessary when evaluating children with hypertension, hypokalaemia, metabolic alkalosis or sexual infantilism.

Rare hypertension as a result of 17alpha-hydroxylase deficiency.

PURPOSE: To investigate CYP 7A1 gene mutations in Chinese patients with 17alpha-hydroxylase deficiency. METHODS: Clinical data were retrospectively analyzed. CYP17A1 mutations were detected in two cases with 17alpha-hydroxylase deficiency. Genomic DNA was isolated from blood samples and eight primers pairs were used to amplify eight exons and exon-intron boundaries of the CYP17A1 gene. The amplified PCR products were purified by agarose gel electrophoresis and then directly sequenced. Sequencing results were compared to the established human CYP17A1 sequence. RESULTS: Two compound mutations were identified: TAC --> AA at codons 436-438 on exon 6, causing the amino acid missense mutation Y329K/418X; and deletion of the 9-bp sequence GACTCTTTC at codons 487-489 on exon 8, causing deletion of three amino acids (Asp-Ser-Phe). CONCLUSION: D487_F489del and Y329K, 418X CYP17A1 mutations were identified in our two patients. A literature review revealed that the main CYP17A1 mutations in the Chinese population are missense and splicing defects, and exons 8 and 6 are most frequently involved.

Dysgerminoma in a nineteen-year-old patient with Swyer's syndrome / Philippine Journal of Obstetrics and Gynecology

Dysgerminomas are the most common type of malignant germ cell tumor. It primarily occurs in women under age thirty. Five percent of cases occur in phenotypic females with dysgenetic gonads.?This paper presents a phenotypically female patient with hypogastric mass and primary amenorrhea. Eight months prior, patient underwent left salpingo- oophorectomy. Physical examination showed? absent secondary sexual characteristics along with normal external female genitalia. Intra-operative findings at that time confirmed the presence of a uterus along with absent right ovary. Hormonal studies revealed increased gonadotropin levels, decreased estrogen and female testosterone levels. Serum LDH was elevated. Karyotyping revealed XY chromosome. Pure gonadal dysgenesis is characterized by abnormal testicular determination. The syndrome, as described by the Swyer in 1955, presents the complete form of "pure" gonadal dysgenesis. This involves the association of the female phenotype, female internal genitalia, normal or tall statue and sexual infantilism with primary amenorrhea. These patients have streak gonads that do not secrete testosterone or Mullerian inhibiting factor, and therefore Mullerian derivatives develop.?

CHD8 interacts with CHD7, a protein which is mutated in CHARGE syndrome.

CHARGE syndrome is an autosomal dominant disorder caused in about two-third of cases by mutations in the CHD7 gene. For other genetic diseases e.g. hereditary spastic paraplegia, it was shown that interacting partners are involved in the underlying cause of the disease. These data encouraged us to search for CHD7 binding partners by a yeast two-hybrid library screen and CHD8 was identified as an interacting partner. The result was confirmed by a direct yeast two-hybrid analysis, co-immunoprecipitation studies and by a bimolecular fluorescence complementation assay. To investigate the function of CHD7 missense mutations in the CHD7-CHD8 interacting area on the binding capacity of both proteins, we included three known missense mutations (p.His2096Arg, p.Val2102Ile and p.Gly2108Arg) and one newly identified missense mutation (p.Trp2091Arg) in the CHD7 gene and performed both direct yeast two-hybrid and co-immunoprecipitation studies. In the direct yeast two-hybrid system, the CHD7-CHD8 interaction was disrupted by the missense mutations p.Trp2091Arg, p.His2096Arg and p.Gly2108Arg, whereas in the co-immunoprecipitation studies disruption of the CHD7-CHD8 interaction by the mutations could not be observed. The results lead to the hypothesis that CHD7 and CHD8 proteins are interacting directly and indirectly via additional linker proteins. Disruption of the direct CHD7-CHD8 interaction might change the conformation of a putative large CHD7-CHD8 complex and could be a disease mechanism in CHARGE syndrome.

[Clinical and molecular genetic analysis for 7 patients from 5 pedigrees with 17a-hydroxylase/17, 20 lyase deficiency].

OBJECTIVE: To investigate the clinical and genetic characteristics of 7 patients from 5 families with 17a-hydroxylase/17,20 lyase deficiency (17OHD) and the CYP17A1 mutation in Chinese. METHODS: Clinical features and laboratory data were collected from 5 families with 17OHD. PCR direct sequencing was performed to screen the mutation of CYP17A1 gene of the patients. Polymerase chain reaction-restriction fragment length polymorphism(PCR-RFLP) and sequencing were performed to screen the mutations of CYP17A1 gene in 288 healthy individuals from Shandong province. RESULTS: Seven patients (5 of them were 46,XX; 2 were 46,XY) had typical clinical presentation of sexual infantilism, hypertension and hypokalemia. Hormone profile indicated decreased plasma cortisol and sex hormones, and elevated blood adrenocorticotrophic hormone (ACTH). TAC329AA and H373L in exon 6 and D487_F489del in exon 8 were identified from the patients. One heterozygote for D487_F489del was identified in 288 healthy controls. CONCLUSION: The TAC329AA and D487_F489del of the CYP17A1 gene were the most frequent mutations in Chinese with 17OHD.There might be certain frequency of heterozygotes for D487_F489del in Chinese population.

Clinical and molecular genetic analysis for 7 patients from 5 pedigrees with 17a-hydroxylase/17, 20 lyase deficiency / 中华医学遗传学杂志

<p><b>OBJECTIVE</b>To investigate the clinical and genetic characteristics of 7 patients from 5 families with 17a-hydroxylase/17,20 lyase deficiency (17OHD) and the CYP17A1 mutation in Chinese.</p><p><b>METHODS</b>Clinical features and laboratory data were collected from 5 families with 17OHD. PCR direct sequencing was performed to screen the mutation of CYP17A1 gene of the patients. Polymerase chain reaction-restriction fragment length polymorphism(PCR-RFLP) and sequencing were performed to screen the mutations of CYP17A1 gene in 288 healthy individuals from Shandong province.</p><p><b>RESULTS</b>Seven patients (5 of them were 46,XX; 2 were 46,XY) had typical clinical presentation of sexual infantilism, hypertension and hypokalemia. Hormone profile indicated decreased plasma cortisol and sex hormones, and elevated blood adrenocorticotrophic hormone (ACTH). TAC329AA and H373L in exon 6 and D487_F489del in exon 8 were identified from the patients. One heterozygote for D487_F489del was identified in 288 healthy controls.</p><p><b>CONCLUSION</b>The TAC329AA and D487_F489del of the CYP17A1 gene were the most frequent mutations in Chinese with 17OHD.There might be certain frequency of heterozygotes for D487_F489del in Chinese population.</p>

Análise clínica e molecular de pacientes com distúrbios do desenvolvimento gonadal / Clinical and molecular analysis of patients with disorders of gonadal development

Introdução: O termo distúrbios do desenvolvimento gonadal (DDG) inclui condições congênitas nas quais o desenvolvimento gonadal é atípico. Estudos feitos em camundongos observaram que alguns genes como o Cbx2 e o Tcf21 interferem na fase inicial do desenvolvimento gonadal, afetando tanto gônadas XX quanto XY. O gene Dhh, por sua vez, codifica o fator de transcrição Dhh, produzido pelas células de Sertoli, que é fundamental para a diferenciação das células de Leydig em gônadas XY. Nos ovários, o gene FOXL2 atua na foliculogênese, sendo fundamental para a formação dos ovários. Objetivos: Analisar clinicamente e pesquisar anormalidades nos genes CBX2, TCF21, DHH e FOXL2 em pacientes portadores de distúrbios do desenvolvimento gonadal 46, XY e 46, XX. Material e Métodos: Foram estudados 60 pacientes (41 com DDG 46, XY e 19 com DDG 46, XX). A análise molecular foi realizada a partir da amplificação gênica por PCR e sequenciamento direto. Resultados: Várias alterações alélicas foram encontradas nos quatro genes, algumas ainda não descritas na literatura. Uma alteração intrônica no gene DHH foi encontrada em um paciente com DDG 46, XY e não foi encontrada em nenhum dos 360 alelos normais estudados (g.IVS2 +29G>A). Estudamos essa variante através da extração do RNA do testículo do paciente afetado, mas não encontramos alteração no RNA; portanto ela parece não ser uma mutação. No gene TCF21, a variante encontrada foi identificada em controles normais. No gene CBX2, das treze alterações encontradas, uma não foi identificada em 206 alelos normais, e há troca de aminoácidos (p.C132R / g.394 T>C). Trata-se de uma variante que pode ter relação com o fenótipo do paciente, portador de DDG 46, XY. No gene FOXL2, das três alterações encontradas, uma não foi identificada em 206 alelos normais; contudo, não há troca de aminoácidos (p.A181A / g.543 C>T). Conclusão: Esse estudo sugere que mutações nos genes CBX2, TCF21, FOXL2 e DHH são causas raras de distúrbios do desenvolvimento...

Introduction: Congenital disorders of gonadal development (DGD) include conditions whose gonadal development is atypical. Studies in mice found that some genes such as Cbx2 and Tcf21 interfere in the initial phase of gonadal development, affecting both XX and XY gonads. Dhh gene, in turn, encodes the transcription factor Dhh, produced by Sertoli cells, which is essential for the differentiation of Leydig cells in XY gonads. In the ovaries, genes as FOXL2 act in folliculogenesis, fundamental to the development of the ovaries. Objectives: To analyze patients with disorders of gonadal development (DGD) 46, XY and 46, XX and research mutations in CBX2, TCF21, DHH and FOXL2 genes. Methods: We analyzed 60 patients (41 DGD 46, XY patients and 19 DGD 46, XX patients). The whole coding region of CBX2, TCF21, DHH and FOXL2 genes were amplified by PCR and direct sequenced. Results: Several allelic variations have been found in the four genes, some not even described by literature. One intronic variation in DHH was described in one patient with 46, XY DGD and it wasnt found in any of the 360 normal control alleles studied (g.IVS2 +29G>A). We studied this variant through RNA extraction from the affected patients testes, but we didnt find any alteration in the RNA, so it doesnt seem to be a mutation. In TCF21 gene, the single variant that was found was identified in normal controls. In CBX2 gene, among the 13 alterations described, one wasnt identified in 206 normal control alleles, and there is aminoacid change (p.C132R / g.394 T>C). This is a variant that may be a mutation, causing the patients phenotype that had 46, XY DGD. In FOXL2, among the 3 variations described, one wasnt indentified in 206 normal control alleles, but there wasnt amino acid change (p.A181A / g.543 C>T).Conclusion: This study suggests that mutations in CBX2, TCF21, FOXL2 and DHH genes are rarely causes of disorders of gonadal development.

Correlation between Karyotype and Phenotype in Turner Syndrome

PURPOSE: In spite of the karyotype and phenotype diversity in Turner syndrome patients, there are few reports about such differences in Korea. We reviewed the data of chromosome abnormalities, clinical manifestations, and comorbidities of Turner syndrome patients in Kyungpook National University Hospital to compare them to the recent hypotheses about sex chromosome gene loci related to Turner symptoms. MATERIALS AND METHODS: We identified the cytologic findings of 92 patients with Turner syndrome and the clinical findings of 62 patients among them. RESULTS: 54.3 percent of patients had 45,X while 45.7 percent showed other karyotype combinations (45,X/46,XX, 45,X/46,XX/47,XXX, 46,X,del(Xp), 46,X,del(Xq), 45,X/46,X,del(Xq), 46,X,i(Xq), 45,X/46,X,i (Xq)). The Turner symptoms found included short neck, high arched palate, broad chest, Madelung deformity, short metacarpals, scoliosis, cubitus valgus, low hair line, webbed neck, edematous extremities, pigmented nevus, and sexual infantilism. The specific diseases associated Turner syndrome included renal abnormalities, congenital heart disease, hearing defects, diabetes mellitus, hyperlipidemia, and decreased bone density. The phenotype of the mosaicism group was milder than that of the monosomy group. In the case of 46,X,del(Xp) and 45,X/46,X,del(Xq) groups, all had skeletal abnormalities, but the 46,X,del(Xq) group had none. In the case of 46,X,del(Xp) group, all showed short statures and skeletal abnormalities, but no sexual infantilism was observed. In the case of 46,X,i(Xq) and 45,X/46,X,i(Xq) groups, they all showed delayed puberty and had primary amenorrhea. CONCLUSION: It is important to study karyotype-phenotype correlations in patients with Turner syndrome to obtain interesting information about the genotype-phenotype correlations related to the X chromosome.

17-Hydroxyprogesterone deficiency as a cause of sexual infantilism and arterial hypertension: laboratory and molecular diagnosis--a case report.

The differential diagnosis of hypertension associated with hypokalemia in infancy and adolescence should necessarily include deficiency of the 17alpha-hydroxylase enzyme, a rare form of congenital adrenal hyperplasia (CAH). In addition to hypertension, the classic syndrome caused by this deficiency is characterized by suppressed production of sex hormones and consequently sexual infantilism. Although rare (1% of all forms of CAH), there appears to be a higher incidence of this syndrome in some population groups. This is a case report on two sisters followed up at the Department of Obstetrics and Gynecology, School of Medicine, Universidade Estadual de Campinas (UNICAMP), who were both found to have the 46,XY genotype with homozygosis for W406R, exon 7 of the CYP17 gene (OMIM 202110). The condition was diagnosed only at puberty when hypergonadotropic hypogonadism resulted in sexual infantilism; however, arterial hypertension had been present since infancy and late diagnosis and lack of timely adequate treatment resulted in complications.