Clinical features of unrecognized congenital adrenal hyperplasia due to 17α-hydroxylase deficiency since adolescence: A case report / Journal of the ASEAN Federation of Endocrine Societies

@#The majority of patients with congenital adrenal hyperplasia (CAH) present with a deficiency of 21-hydroxylase or 11-beta-hydroxylase, which account for 90% and 7% of cases, respectively. However, CAH due to 17α-hydroxylase deficiency (17OHD) is an extremely rare form of CAH (<1% of all CAH cases) that leads to a deficiency of cortisol and sex steroids, along with features of aldosterone excess. This is a case of a 51-year-old single female who was referred to us for the evaluation of new-onset hypertension and hypokalaemia of one-year duration. She was born out of a second-degree consanguineous marriage and reared as a female. She was diagnosed to have testicular feminization syndrome when she presented with a history of primary amenorrhea, absence of secondary sexual characteristics, and bilateral labial swellings at pubertal age. Subsequently, she underwent gonadectomy at the age of 16. Due to the presence of hypertension, metabolic alkalosis and bilaterally enlarged adrenals on CT scan, 46, XY disorders of sexual development (DSD) was considered. A karyotype confirmed the presence of 46, XY chromosomal sex, and genetic analysis revealed a mutation in the CYP17A1 gene, thus confirming the diagnosis of 17a-hydroxylase deficiency.

Epididymis cell atlas in a patient with a sex development disorder and a novel NR5A1 gene mutation / 亚洲男科学杂志(英文版)

This study aims to characterize the cell atlas of the epididymis derived from a 46,XY disorders of sex development (DSD) patient with a novel heterozygous mutation of the nuclear receptor subfamily 5 group A member 1 (NR5A1) gene. Next-generation sequencing found a heterozygous c.124C>G mutation in NR5A1 that resulted in a p.Q42E missense mutation in the conserved DNA-binding domain of NR5A1. The patient demonstrated feminization of external genitalia and Tanner stage 1 breast development. The surgical procedure revealed a morphologically normal epididymis and vas deferens but a dysplastic testis. Microfluidic-based single-cell RNA sequencing (scRNA-seq) analysis found that the fibroblast cells were significantly increased (approximately 46.5%), whereas the number of main epididymal epithelial cells (approximately 9.2%), such as principal cells and basal cells, was dramatically decreased. Bioinformatics analysis of cell-cell communications and gene regulatory networks at the single-cell level inferred that epididymal epithelial cell loss and fibroblast occupation are associated with the epithelial-to-mesenchymal transition (EMT) process. The present study provides a cell atlas of the epididymis of a patient with 46,XY DSD and serves as an important resource for understanding the pathophysiology of DSD.

Atendendo mulheres com cariótipo 46, XY / Attending women with 46, XY karyotype

As diferenças ou distúrbios do desenvolvimento sexual (DDS) compreendem um grupo heterogêneo de condições congênitas que resultam na discordância entre os cromossomos sexuais, as gônadas e/ou o sexo anatômico de um indivíduo. A classificação desses distúrbios é baseada no cariótipo conforme o Consenso de Chicago de 2006 e substitui os termos pseudo-hermafroditismo, hermafroditismo e intersexo. O objetivo desta revisão é fornecer ao ginecologista conhecimentos básicos sobre a etiologia, fisiopatologia e orientações das principais anormalidades de DDS para uma avaliação diagnóstica e terapêutica no atendimento de mulheres na infância, adolescência e em idade adulta com cariótipo 46,XY. O diagnóstico deve ser realizado pela interação entre o exame clínico as dosagens hormonais, os exames de imagem e a análise genética, desde o cariótipo até o estudo de alterações dos genes por técnicas de biologia molecular. O tratamento é realizado de acordo com a etiologia e inclui intervenções cirúrgicas como a gonadectomia e plásticas sobre a genitália externa, terapia de reposição hormonal e apoio psicológico. São necessárias a individualização dos casos e uma equipe interdisciplinar, para um atendimento adequado às mulheres com cariótipo 46,XY.(AU)

Differences or disorders of sexual development (DSDs) comprise a heterogeneous group of congenital conditions that result in the disagreement between an individual's sex chromosomes, gonads and/or anatomic sex. The classification of these disorders is based on the karyotype according to the 2006 Chicago Consensus and replaces the terms pseudohermaphroditism, hermaphroditism and intersex. The aim of this review is to provide the gynecologist with basic knowledge about the etiology, pathophysiology and guidelines of the main abnormalities of DDS for a diagnostic and therapeutic evaluation in the care of women in childhood, adolescence and adulthood with a karyotype 46,XY. The diagnosis must be made by the interaction between clinical examination hormonal measurements, imaging and genetic analysis from the karyotype to the study of gene alterations by molecular biology techniques. Treatment is carried out according to the etiology and includes surgical interventions such as gonadectomy and plastic surgery on the external genitalia, hormone replacement therapy and psychological support. Individualization of cases and an interdisciplinary team are required to provide adequate care for women 46,XY karyotype.(AU)

Surgical management and molecular diagnosis of persistent Müllerian duct syndrome in Chinese patients / 亚洲男科学杂志(英文版)

Persistent Müllerian duct syndrome (PMDS) is a rare clinically and genetically overlapping disorder caused by mutations in the anti-Müllerian hormone (AMH) gene or the anti-Müllerian hormone receptor type 2 (AMHR2) gene. Affected individuals present uterus and tubes in normally virilized males and are discovered unexpectedly during other surgeries. Since it is rare and complex, a definitive clinical diagnosis can be missed, and there are no guidelines regarding how to deal with the uterus. In the present study, exome sequencing and Sanger verification were performed for causal variants in 12 PMDS patients. Preoperative diagnoses were made by positive exome sequencing in 8 patients. Of them, 7 patients evoked on the basis of ultrasound indicating bilateral testes on the same side of the body. Twelve different AMH variants (2 frameshift/nonsense, 1 deletion, 8 missense, and 1 in-frame) in 9 patients and 6 different AMHR2 variants (5 missense and 1 splicing) in 3 patients were identified. Seven variants were classified as "pathogenic" or "likely pathogenic", and 4 of them were novel. All but two patients with AMH defects showed low serum AMH concentrations, but all patients with AMHR2 defects showed elevated AMH levels. During surgery, an abnormal vas deferens was observed in half of the patients. Eight patients underwent orchidopexy with uterine preservation. Of them, 2 patients presented complications including irreducible cryptorchidism, and 3 patients developed Müllerian remnant cysts. Three patients underwent subtotal hysterectomy. Of them, one patient had complication of injury to the vas deferens, and one had hemorrhage after operation. This is the first report of PMDS involving a large Chinese population. The present study not only expands the variation spectrum but also provides clinical experience about the management of the uterus.

Identification of a novel variant of SRD5A2 gene in a child featuring steroid 5α-reductase type 2 deficiency / 中华医学遗传学杂志

OBJECTIVE@#To explore the clinical characteristics and genetic basis of a child with 5α-reductase type 2 deficiency.@*METHODS@#Clinical data of the child was retrospectively analyzed. Targeted capture-next generation sequencing and Sanger sequencing were carried out to detect potential variants.@*RESULTS@#The patient's main features included micropenis and hypospadia. He was found to harbor compound heterozygous c.680G>A (p.R227Q) and c.3G>T (p.M1I) variants of the SRD5A2 gene. Among these, c.680G>A (p.R227Q) was inherited from his father and was a known pathogenic mutation, while c.3G>T (p.M1I) was inherited from his mother and was unreported previously.@*CONCLUSION@#The compound heterozygous variants of the SRD5A2 gene probably underlay the disease in this child, who was eventually diagnosed with 5α-reductase 2 deficiency.

Genetic analysis of 46,XY disorders of sex development in children caused by a new NR5A1 gene variant / 中华医学遗传学杂志

OBJECTIVE@#To explore the genetic basis for a child with 46,XY disorders of sex development (DSD) and explore its genotype-phenotype correlation.@*METHODS@#The child was subjected to whole exome sequencing (WES), and exons 1 to 7 of NR5A1 were subjected to multiplex ligation-dependent probe amplification (MLPA) analysis.@*RESULTS@#The patient presented with rudimentary vulva of a female with Tanner stage 1. B-mode ultrasonography has detected ovary and uterus. The child was found to have a chromosome karyotype of 46,XY. WES revealed that the patient has harbored heterozygous deletion of exon 5 of the NR5A1 gene, which was a novel pathogenic variant inherited from the mother. No abnormality was found in the father.@*CONCLUSION@#The main symptoms of 46,XY DSD children are insufficient external genitalia masculinization, for which variants of the NR5A1 gene are an important cause. WES has improved the detection rate of genetic variants and provided a solid basis for genetic counseling of the affected families.

Novel homozygous mutation in a colombian patient with persistent müllerian duct syndrome: expanded phenotype

ABSTRACT The anti-Müllerian hormone triggers the regression of uterus and fallopian tubes in male embryos; if there are problems in the synthesis or action of this protein, Müllerian structures persist in an otherwise phenotypic male. The most frequent clinical presentation of Persistent Mullerian Duct syndrome is cryptorchidism and inguinal hernia. The few cases reported in adults are incidental findings or inguinal hernias. However, we present an adult male with history of bilateral cryptorchidism with unsuccessful orchidopexy, who presents with a large abdominal mass with the finding of a seminomatous tumor and persistence of Müllerian structures, in whom the variant c.916delC (p.Leu306Cysfs*29) in the AMHR2 gene not previously reported was documented.

Abordaje del recién nacido con alteraciones del desarrollo sexual / Newborn approach with disorders of sexual development

Resumen Introducción: Las alteraciones del desarrollo sexual en el recién nacido no es una condición infrecuente durante la práctica médica pero sí resulta ser un reto tanto en el abordaje diagnostico como en el terapéutico. Se definen como el conjunto de condiciones en donde el desarrollo del sexo cromosómico, gonadal o anatómico es atípico. Objetivos: Realizar un abordaje integral de las alteraciones del desarrollo sexual y reconocer la importancia de los equipos transdisciplinarios para el manejo de esta patología. Metodología: Se realizó una búsqueda de la literatura con las palabras clave Disorders of sex development, Ovotesticular disorders of sex development, True Hermaphroditism, Gonadal dysgenesis, Adrenal hyperplasia, congenital en cinco bases de datos bibliográficas, se limitó la búsqueda para artículos en idioma español o inglés de los últimos 10 años. Resultados: Se obtuvieron110 artículos de los cuales 36 fueron incluidos en esta revisión, los artículos revisados eran artículos originales, presentación de casos, consensos y artículos de revisión. Conclusiones: La sensibilización al personal de salud sobre esta condición es fundamental para realizar un diagnóstico y tratamiento oportuno, con el objetivo de evitar complicaciones en la salud del recién nacido. La asignación del sexo es uno de los problemas más relevantes para el manejo de esta patología; esta decisión deberá ser tomada por el equipo transdisciplinario de especialistas con experiencia en el tema en donde se realice una evaluación detallada e individual de cada caso.

Abstract Introduction: Disorder of sexual development in newborn is not an infrequent condition during medical practice, but it does prove to be a challenge both in diagnostic and in therapeutic approaches. It is defined as the set of conditions in which the development of chromosomal, gonadal or anatomical sex is atypical. Objectives: To carry out a comprehensive approach to sexual development alterations and to recognize the importance of transdisciplinary teams for the management of this pathology. Methodology: A search of review literature was made with the key words Disorders of sex development, Ovotesticular disorders of sex development, true hermaphroditism, gonadal dysgenesis, and congenital adrenal hyperplasia in five biomedical databases. The search has been limited to Spanish or English language articles of the last 10 years. Results: 110 articles were reviewed, of which 36 were included, they were original articles, case presentations, consensus and review articles. Conclusions: In order to avoid complications in newborn, health personnel should be sensitized, regarding this condition is essential to timely diagnosis and treatment. Assignment of sex is one of the most relevant problems for the management of this condition; this decision must be made by a transdisciplinary team of specialists with experience in the subject where a detailed and individual evaluation of each case is carried out.

Male pseudohermaphroditism with os clitoris in three dogs

Two American Cocker Spaniels and one Bichon Frise were presented to our veterinary teaching hospital with an enlarged clitoris. Diagnostic imaging showed that the structure was composed of bony material. Exploratory laparotomy revealed uterine-like structures and testes which had an epididymis unilaterally. Surgical removal of internal genitalia, gonads and protruded clitoris were performed well. Histological evaluation revealed; inactive testes, female internal genital tracts with ambisexual ductal remnants, and prominent ossification in the clitoris. All 3 cases were diagnosed with male pseudohermaphroditism. In author's knowledge, this is the first report in Bichon Frise dog with os clitoris and also, it describes not common cases in small dog breeds with os clitoris.

Síndrome de persistencia de los conductos mullerianos: una rara entidad que debe ser conocida / Persistent Müllerian Duct Symdrome: a rare anomaly that must be known

Introducción: El síndrome de persistencia de los conductos müllerianos es un raro trastorno de la diferenciación sexual con menos de 300 casos publicados, que se caracteriza por la presencia en la persona afectada de ambos sistemas reproductores masculino y femenino. Un varón con cariotipo XY fenotípicamente masculino en quien el conducto de Müller (útero, trompas, 2/3 superior de la vagi-na) no sufrió regresión. Caso clínico: Masculino de 14 meses de edad ingresado en el Hospital de Especialidades del Seguro Social para laparoscopía diagnostica por criptorquidia bilateral con testículos no palpables y pene normal. En la laparoscopía se identiicó trompas, útero y 2/3 superior de la vagina. Además, se tomó biopsia de ambas gónadas que conirmó presencia de tejido testicular normal para la edad. Con estos datos se programa para orquidopexia bilateral más histerectomía, colpectomía y salpingectomía bilateral. Es controlado en consulta externa de endocrinología y cirugía con evolución normal. Conclusiones: El síndrome de persistencia de los conductos mül-lerianos es muy raro debe sospecharse en masculinos con criptorquidia bilateral con testículos no palpables y pene normal. El abordaje inicial debe ser laparoscopía diagnóstica con toma de biopsia de ambas gónadas y luego en la segunda intervención ya con el reporte de patología proceder a la orquidopexia bilateral más la remoción de los elementos del conducto de Müller...(AU)

La creación clínica de normas sexuales. Nosología, patologización y contramodelos sexuales en la Penitenciaría Nacional de Buenos Aires (Argentina, 1901-1904) / A criação clínica de normas sexuais. Nosologia, patologização e contramodelos sexuais na Penitenciaría Nacional de Buenos Aires (Argentina, 1901-1904) / The clinical creation of sex norms. Nosology, pathologization and sexual counter models at the Penitenciaría Nacional de Buenos Aires (Argentina, 1901-1904)

Resumen El siguiente artículo se ocupa del problema de la construcción de nosologías médico-psiquiátricas referidas a la sexualidad, tomando para ello los casos de inversión sexual (travestismo) analizados por Francisco de Veyga en el Servicio de Observaciones de Presuntos Alienados de la Penitenciaría Nacional, en Argentina, a principios del siglo XX. El interés reside en la operatoria por la cual el alienista construye categorías nosográficas ex nihilo, para dar cuenta de las formas de vida y subjetivación que ciertos sujetos desarrollaban y que amenazaban el canon de la normalidad. A su vez, en la voz de De Veyga se traslucen algunos aspectos sobre la moralidad en la vida porteña, que contrastaba con la escena de peligro que éste buscaba plantear. Con ello, interesa analizar un caso específico, donde el alienismo local comienza a intervenir y teorizar, sobre cuerpos y subjetividades disidentes, a partir de la construcción de un discurso grotesco, para calificar formas de vida en los márgenes de la normalidad que buscaba establecerse, propio de los efectos de poder normalizadores que Foucault reconociera en las pericias médico legales.

Resumo Este trabalho toma como objeto a construção de nosologias médico-psiquiátricas em relação à sexualidade, a partir de casos de inversão sexual (travestismo) analisados ​​por Francisco de Veyga no Servicio de Observaciones de Presuntos Alienados de la Penitenciaría Nacional na Argentina, no início do século XX. Nosso interesse reside na operação pela qual o alienista constrói ex nihilo categorias nosográficas para explicar os modos de vida e subjetividade que certos indivíduos desenvolveram ameaçando o cânone da normalidade. Por sua vez, acreditamos que a voz de De Veyga reflete alguns aspectos da moralidade cotidiana em Buenos Aires, que contrastam com o cenário de perigo que ele procurou estabelecer. Com isso, queremos analisar um caso específico onde o alienismo local começa a intervir e teorizar sobre corpos e subjetividades dissidentes, a partir da construção de um discurso grotesco para qualificar as formas de vida à margem da normalidade que se pretendia estabelecer. Isto se assemelha aos efeitos de poder normalizador que Foucault reconhecera nas perícia médico-legais.

Abstract This paper's object is the creation of medical-psychiatric nosologies referring to sexuality in cases of sexual inversion (transvestism) analyzed by Francisco de Veyga in the Servicio de Observaciones de Presuntos Alienados de la Penitenciaría Nacional (National Penitentiary's Presumed Alienated Observation Service) in Argentina, at the beginning of the 20th century. Our interest lies in the operation by which the alienist built ex nihilo nosographic categories to account for the forms of life and subjectivation that certain subjects developed, which threatened the canon of normality. In addition, we will consider that the voice of De Veyga showed some aspects about morality in the life of Buenos Aires that contrasted with a scene of danger he wanted propose. Our interest is to analyze a specific case where local alienism intervenes and theorizes about dissenting bodies and subjectivities, with the construction of a grotesque discourse to qualify forms of life in the margins of normality, typical of the normalizing power effects that Foucault recognized in medical legal examinations.

O debate legislativo carioca sobre a "mudança da homossexualidade": ciência, política e religião / The debate in the "carioca" legislature about "changing homosexuality": science, politics and religion / El debate legislativo "carioca" sobre el "cambio de la homosexualidad": ciencia, política y religión

Resumo O artigo analisa o debate na mídia impressa em torno do projeto de lei 717/03, apresentado na Assembleia Legislativa do Rio de Janeiro em agosto de 2003, que previa o uso de verbas públicas para a "mudança da homossexualidade". Foram utilizadas como fontes de pesquisa notícias sobre este projeto publicadas em jornais e revistas de grande circulação estadual e nacional, considerando-se os autores, os atores sociais e as categorias citadas nos diferentes tipos de matéria, bem como os argumentos contrários e favoráveis à proposta legislativa. Verificamos assim o modo como argumentos relativos aos campos científico, religioso e político ressignificaram as relações entre natureza/cultura e normal/patológico, operando de modo especifico, e por vezes contraditório, com valores caros às sociedades modernas contemporâneas, como igualdade entre os homens e livre arbítrio individual.

Abstract The article analyzes the debate in printed media about the 717/03 law proposal which was presented at the Legislative Assembly of Rio de Janeiro in August 2003. This bill provided for the use of public funds for the "change of homosexuality." News about this project published in newspapers and magazines of statewide and nationwide coverage were used in the research considering the authors, social actors and categories that appeared in the different types of material, as well as the opposing and favorable arguments about the Legislative proposal. We have thus verified how arguments related to the scientific, religious and political fields have reconfigured the relations between nature/culture and normal/pathological, operating in a specific and sometimes contradictory way, with dear values to contemporary modern societies, as equality among men and individual will.

Resumen El artículo analiza el debate en los medios impresos en torno al proyecto de ley 717/03, presentado en la Asamblea Legislativa de Río de Janeiro en agosto de 2003, que preveía el uso de fondos públicos para el "cambio de la homosexualidad". Se utilizaron como fuentes de investigación noticias sobre este proyecto, publicadas en periódicos y revistas de gran circulación estatal y nacional, considerando los autores, los actores sociales y categorías citadas en los diferentes tipos de noticia, así como los argumentos contrarios y favorables sobre la propuesta legislativa. De esta forma verificamos el modo como argumentos relativos a los campos científico, religioso y político resignificaron las relaciones entre naturaleza / cultura y normal / patológico, operando de modo específico, y a veces contradictorio, con valores importantes a las sociedades modernas contemporáneas, como la igualdad entre los hombres y el libre albedrío.

Female with 46, XY karyotype

Disorders of sex development (DSD) are congenital conditions characterized by atypical development of chromosomal, gonadal, and phenotypic sex. 46, XY DSD can result from disorders of testicular development or disorders of androgen synthesis/action. Prophylactic gonadectomy should be considered in patients with 46, XY DSD because of the increased risk of gonadal malignancy. We report two rare cases of 46, XY DSD, including XY pure gonadal dysgenesis and complete androgen insensitivity syndrome, who underwent a prophylactic gonadectomy.

46, XY Partial Gonadal Dysgenesis diagnosed in adulthood

@#Partial Gonadal Dysgenesis (PGD) is a rare disorder of sexual development defined by sexual ambiguity and the presence of mullerian structures due to variable degrees of testicular dysgenesis in individuals with a non-mosaic 46, XY karyotype. Due to incomplete gonadal development, the external phenotype would rely on the degree of testicular function. The dysgenetic gonads found in PGD have high risk for malignant transformation. Although ambiguous genitalia was noted upon birth, a case diagnosed in adulthood is presented. Discordance between sex of rearing and the psychosexuality of the patient prompted consult. On work up, 46, XY was noted on karyotyping but presence of a uterus was seen on ultrasound. Hormonal assay revealed elevated levels of FSH and LH, while testosterone levels were low and estradiol was high. Gonadoblastoma was noted on final histopathologic evaluation. This report shall tackle thorough preoperative evaluation, surgical and postoperative management of individuals with PGD.

Persistent Mullerian Duct Syndrome: a rare entity with a rare presentation in need of multidisciplinary management

ABSTRACT Main findings: A typical male looking adolescent with a legal female gender assignment presented with haematuria. Investigations led to the diagnosis of Persistent Mullerian Duct Syndrome. The condition is indeed a rare entity that needs a multidisciplinary team management. Case hypothesis: A case of Persistent Mullerian Duct Syndrome undiagnosed at birth because karyotyping was defaulted, thus resulting in a significant impact on the legal gender assignment and psychosocial aspects. Promising future implications: The reporting of this case is important to create awareness due to its rarity coupled with the rare presentation with hematuria as a possible masquerade to menstruation. There were not only medical implications, but also psychosocial and legal connotations requiring a holistic multidisciplinary management.

Anomalias do desenvolvimento sexual / Abnormalities of sexual development

As anormalidades da diferenciação sexual são infrequentes na prática clínica. A caracterização de uma ampla variedade de síndromes tem sido muitas vezes confusa, necessitando, com relativa frequência, a consulta de múltiplos livros e uso constante de referências para uma correta compreensão. O presente artigo tem a proposta de revisar as entidades mais frequentes, seus métodos diagnósticos e sua conveniente orientação.(AU)

Abnormal sexual differentiation is not frequently seen in an individual clinician's practice. The categories of many syndromes in this area require special and constant references to review many papers and books to understand these abnormalities. In this paper, the most frequent syndromes are described, and their diagnostic methods and proposals for correct orientation are provided.(AU)

Advances in the diagnosis and hormone replacement treatment of 46, XY disorders of sex development / 中华男科学杂志

Disorders of sex development (DSD) is defined as a congenital condition or atypical development of the chromosomal, gonadal, or anatomic sex. The diagnosis, gender assignment, and treatment of DSD require the guidance from experienced multidisciplinary teams. So far there has been no consensus about it in China. Due to dysgenetic gonads, defects in sex steroid biosynthesis or action, or gonadectomy during the prepubertal years, those with DSD suffer from hypogonadism. The hormone replacement therapy of DSD aims at general physiological health and long-term prognosis as well as the avoidance of unnecessary genital and gonadal surgery. This review focuses on the advances in the studies of the diagnosis and hormone replacement therapy of 46,XY DSD.

Clinical features and StAR gene mutations in children with congenital lipoid adrenal hyperplasia / 中国当代儿科杂志

This article reported the clinical manifestations, steroid profiles and adrenal ultrasound findings in two unrelated Chinese girls with lipoid congenital adrenal hyperplasia (LCAH). Direct DNA sequencing and restriction fragment length polymorphism (RFLP) analysis were used to identify the mutations of steroidogenic acute regulatory protein (StAR) gene. The two patients with 46,XX karyotype, presented hyperpigmentation, growth retardation, and hyponatremia. Steroid profiles analysis revealed elevated plasma adrenocorticotrophic hormone levels, decreased or normal serum cortisol levels and low levels of androgens. Ultrasound examinations revealed that enlarged adrenals in patient 1 and normal adrenals in patient 2. Direct DNA sequencing of StAR gene showed a reported homozygous for c.772C>T(p.Q258X) in patient 1. Compound heterozygous for c.367G>A(p.E123K) and IVS4+2T>A (both novel mutations) were found in patient 2, inherited from her mother and father respectively. The amino acid of mutant position of the novel p.E123K was highly conserved in ten different species and was predicted to have impacts on the structure and function of StAR protein by the PolyPhen-2 prediction software. RFLP analysis revealed three bands (670, 423 and 247 bp) in patient 2 and her father and two bands (423 and 247 bp) in her mother and 50 controls. It is concluded that LCAH should be considered in girls with early onset of adrenal insufficiency and that steroid profiles, karyotype analysis, adrenal ultrasound and StAR gene analysis may be helpful for the definite diagnosis of LCAH.