Analysis of clinical phenotype and genotype of Chinese children with disorders of sex development / 中华儿科杂志

Objective: To explore the heterogeneity and correlation of clinical phenotypes and genotypes in children with disorders of sex development (DSD). Methods: A retrospective study of 1 235 patients with clinically proposed DSD in 36 pediatric medical institutions across the country from January 2017 to May 2021. After capturing 277 DSD-related candidate genes, second-generation sequencing was performed to analyzed the heterogeneity and correlation combined with clinical phenotypes. Results: Among 1 235 children with clinically proposed DSD, 980 were males and 255 were females of social gender at the time of initial diagnosis with the age ranged from 1 day of age to 17.92 years. A total of 443 children with pathogenic variants were detected through molecular genetic studies, with a positive detection rate of 35.9%. The most common clinical phenotypes were micropenis (455 cases), hypospadias (321 cases), and cryptorchidism (172 cases) and common mutations detected were in SRD5A2 gene (80 cases), AR gene (53 cases) and CYP21A2 gene (44 cases). Among them, the SRD5A2 mutation is the most common in children with simple micropenis and simple hypospadias, while the AMH mutation is the most common in children with simple cryptorchidism. Conclusions: The SRD5A2 mutation is the most common genetic variant in Chinese children with DSD, and micropenis, cryptorchidism, and hypospadias are the most common clinical phenotypes. Molecular diagnosis can provide clues about the biological basis of DSD, and can also guide clinicians to perform specific clinical examinations. Target sequence capture probes and next-generation sequencing technology can provide effective and economical genetic diagnosis for children with DSD.

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.

Why are mini-implants lost: The value of the implantation technique!

The use of mini-implants have made a major contribution to orthodontic treatment. Demand has aroused scientific curiosity about implant placement procedures and techniques. However, the reasons for instability have not yet been made totally clear. The aim of this article is to establish a relationship between implant placement technique and mini-implant success rates by means of examining the following hypotheses: 1) Sites of poor alveolar bone and little space between roots lead to inadequate implant placement; 2) Different sites require mini-implants of different sizes! Implant size should respect alveolar bone diameter; 3) Properly determining mini-implant placement site provides ease for implant placement and contributes to stability; 4) The more precise the lancing procedures, the better the implant placement technique; 5) Self-drilling does not mean higher pressures; 6) Knowing where implant placement should end decreases the risk of complications and mini-implant loss.

O uso de mini-implantes trouxe grandes contribuições ao tratamento ortodôntico. Essa demanda gerou curiosidade científica sobre os procedimentos e técnicas de implantação. Entretanto, instabilidades desses dispositivos ocorrem por motivos ainda não totalmente esclarecidos. Objetiva-se, com esse trabalho, relacionar a técnica de implantação com a taxa de sucesso dos mini-implantes por meio das seguintes hipóteses: 1) áreas com osso alveolar pobre e com pouco espaço inter-radicular levam à inadequada implantação; 2) diferentes áreas requerem distintos tamanhos de mini-implantes! O tamanho do implante deve acompanhar o diâmetro do osso alveolar; 3) a correta determinação do local em que será colocado o mini-implante facilita a instalação e contribui para a estabilidade; 4) quanto mais precisa for a lancetagem, melhor será a técnica de implantação; 5) autoperfuração não significa alta pressão; 6) saber onde finalizar a implantação diminui a incidência de complicações e de perda dos mini-implantes.

Intersexuality in a crab-eating fox (cerdocyon thous) / Intersexualidade em uma raposa (cerdocyon thous)

Intersexuality is a reproductive pathology that has been described in wild animals in recent years. However, its occurrence and consequences remain obscure and therefore all aspects of this reproductive disorder deserve attention. The aim of this study is to report a case of intersexuality with probable absence of gonadal tissue in the crab-eating fox (Cerdocyon thous) native to Brazil. The animal has male external genitalia, but its prepuce and penis were both hypoplastic. Because of a clinical suspicion of bilateral cryptorchidism, a laparotomy was performed and the absence of prostate and gonads were revealed. The procedure also revealed vas deferentia, extending laterally from the each side of the bladder basis to the right and left abdominal wall muscles. The animal died one month later, and post mortem examination confirmed the absence of prostatic and gonadal tissues. Muscular structures similar to uterine horns and cervix were founded macroscopically and confirmed by optic microscopy. In addition, post mortem findings corroborate with penis hypoplasia, since penile bone presence was observed. The vasa deferentia had a normal tissue structure, although hypoplastic. In conclusion, the case of a crab-eating fox (Cerdocyon thous) reported here represents a proved intersexual animal with probable absence of gonadal tissue.

A intersexualidade é uma das patologias reprodutivas, hereditária e/ou congênita, que têm sido mais reportada em animais selvagens nos últimos anos. Entretanto, suas ocorrências e conseqüências permanecem obscuras, sendo que todos os aspectos relacionados a este distúrbio reprodutivo merecem atenção. O objetivo deste estudo foi relatar um caso de intersexualidade com provável ausência de tecido gonadal em uma raposa (Cerdocyon thous) do Brasil. O animal apresentava sexo fenotípico masculino, mas seu prepúcio e pênis eram pequenos. Devido a uma suspeita clínica de criptorquidismo bilateral, foi realizada uma laparotomia, sendo, no procedimento cirúrgico, revelada a ausência de próstata e gônadas. Os ductos deferentes foram localizados lateralmente à bexiga, entendendo-se desde a sua base, inserindo-se na musculatura da parede abdominal direita e esquerda. Um mês após, o animal morreu e os achados necroscópicos confirmaram a ausência de tecidos prostático e gonadal. Entretanto, uma estrutura muscular histologicamente semelhante a cornos e cérvix uterinos foram encontradas. Além disso, pelo mesmo método, ratificou-se a ausência de próstata e o pênis exibiu aspecto normal contendo osso peniano. Os ductos deferentes apresentaram estrutura tecidual normal, porém hipoplásicos. Concluiu-se que o caso reportado no presente trabalho representa um exemplo de intersexualidade com provável ausência de tecido gonadal em um animal da espécie Cerdocyon thous.

Unilateral cryptorchidism in Nigerian sahel bucks / Criptorquidia unilateral en cabras sahel nigerianas

Out of 1608 Nigerian Sahel male goats (bucks) examined for cryptorchidism in an abattoir, 9 (0.6 percent) had right unilateral cryptorchidism. The coat colour-specific prevalence was highest among the brown bucks (2.1 percent); and was 0.8 percent, 0.6 percent, and 0.3 percent among black, white, back-and-white bucks, respectively. The condition was not found among bucks with brown-and-black, brown-and-white, and multiple coat colours. The right and left testes of normal bucks and the descended testes of cryptorchid bucks had comparable gross testicular measurements, but the retained cryptorchid testes were smaller in size. The estimates of the testicular measurements showed that testicular weights (with the entire epididymes), peripheral longitudinal lengths and mid-circumferences of the cryptorchids were reduced by 5.8-6.5, 1.8-1.9, and 1.7-1.8 folds, respectively, when compared with the normal values; an indication that reduction in weight was the most remarkable index of change in testicular size. In 2 cases (20 percent), cryptorchid testes were at a subcutaneous location, embedded in a subcutaneous fascia in the ventral perineal region, while in the other 8 cryptorchid cases (80 percent), the testes were in the abdomen. Histopathological changes in the cryptorchid testes included hypoplasia, degeneration, interstitial non-suppurative inflammation and fibroplasia. This is the first report of cryptorchidism in the Sahel goat and the first evidence that cryptorchid testis may be located subcutaneously in the goat.

De las 1608 cabras Sahel Nigerianas macho examinadas para criptorquidismo en un matadero, 9 (0,6 por ciento) tuvieron criptorquidia unilateral derecha. La prevalencia en relación al color específico del pelaje fue mayor entre las cabras marrones (2,1 por ciento), y fue de 0,8 por ciento, 0,6 por ciento y 0,3 por ciento entre cabras de color negro, blanco, y blanco/negro respectivamente. La condición no fue encontrada entre las cabras con pelajes marrón y negro, marrón y blanco, y pelajes de múltiples colores. Los testículos derecho e izquierdo de las cabras normales y los testículos descendentes de las cabras con criptorquídia tuvieron mediciones testiculares comparables, pero los testículos retenidos por criptorquídia fueron de menor tamaño. Las estimaciones de las mediciones testiculares mostraron que los pesos testiculares (con todo el epidídimo), la longitud periférica y la circunferencia media de las criptorquídicas fueron reducidas por 5,8-6,5; 1,8-1,9 y 1,7-1,8 pliegues respectivamente, en comparación con el los valores normales; una indicación que la reducción de peso fue el índice de cambio más notable en el tamaño testicular. En 2 casos (20 por ciento), los testículos criptorquídicos se encontraron en una ubicación subcutánea, inmersos en una fascia subcutánea en la región perineal ventral, mientras que en los otros 8 casos criptorquídicos (80 por ciento), los testículos fueron encontrados en el abdomen. Cambios histopatológicos en los testículos criptorquídicos incluyeron hipoplasia, degeneración, inflamación intersticial no supurativa y fibroplasia. Este es el primer informe de criptorquidia en cabras Sahel y la primera evidencia de que los testículos criptorquídicos pueden ser localizados por vía subcutánea en la cabra.

Síndrome de Aarskog: hallazgos fenotípicos en una cohorte de pacientes / Aarskog syndrome: phenotypic findings in a cohort of patients

Se presentan los hallazgos fenotípicos de 7 pacientes diagnosticados de síndrome de Aarskog en el servicio de Genética del Hospital Pediátrico Docente William Soler. Las características fenotípicas que estuvieron presentes en todos los pacientes fueron el pico de viuda, las extremidades cortas y la braquidactilia. Les siguieron en orden de frecuencia (85 por ciento) la nariz pequeÑa, el puente nasal ancho y el filtrum largo y ancho. Otras dismorfias faciales encontradas (71 por ciento) fueron la frente amplia, las narinas antevertidas, el hipertelorismo, el cuello corto y el surco simiano. Se discute la posibilidad de que exista algún sesgo de detección debido a que el examinador presta mayor atención a la cara que a otros segmentos corporales. La criptorquidia, que distingue y da nombre al síndrome, se encontró en un porcentaje menor de individuos (60 por ciento). En dos casos se encontró hipoplasia renal, hallazgo ocasional en la literatura consultada. En ningún caso se constató retraso mental. Las diferencias fenotípicas halladas pudieran atribuirse a las diferencias moleculares reportadas en la literatura.

The phenotypic fndings of 7 patients who were diagnosed Aarskog syndrome in the Service of Genetics of William Soler Pediatric Teaching Hospital were presented. The phenotypic characteristics appearing in all patients were widow's peak, short extremities and brachydactilia. They were followed in order of frequency (85 percent) by small nose, wide nasal bridge and long and wide filtrum. Other facial dismorphies (71 percent) were wide forehead, anteverted narines, hypertelorism, short neck and simian crease. It is discussed the possibility that there is some bias of detection due to the fact that the examiner pays more attention to the face than to other body segments. Criptorchydia, that distinguishes and gives name to the syndrome, was found in a lower percent of individuals (60 percent). Renal hypoplasia, an occasional finding in the consulted literature, was observed in 2 cases. Mental retardation was not confirmed in any case. The phenoptypic differences detected could be attributed to mollecular differences reported in literature.

Aumento del daño en el ADN y estrés oxidativo en espermatozoides de pacientes con oligozoospermia idiopática y antecedentes de criptorquidismo / Extent of sperm DNA damage in spermatozoa from men examined for infertility. Relationship with oxidative stress

Background: Cryptorchidism and oligozoospermia are clinical conditions closely associated with impaired fertility. Oxidative stress and related sperm DNA damage have been identified as significant causes of male infertility. Aim: To determine the extent of sperm nuclear DNA damage in patients affected with idiopathic oligozoospermia or undescended testes and to examine its relationship with oxidative stress. Patients and methods: We studied 20 patients with idiopathic oligozoospermia and 18 with undescended testes (who previously underwent orchiopexy) and 25 normozoospermic healthy controls. All subjects underwent semen analysis. Sperm DNA damage was evaluated by the sperm chromatin structure assay/flow cytometry (SCSA-FCM) and by the dUTP-biotin nick end labeling (TUNEL) assay. Levels of reactive oxygen species (ROS) and total antioxidant capacity (TAC) were assessed by a chemiluminescence assay. Results: DFI (percentage of sperm with denatured DNA) values and percentage of TUNEL positive cells were significantly greater in patients with oligozoospermia (DFI: 28.8±5.6; TUNEL+: 26.9±3.0) or cryptorchidism (DFI: 26.4±10.1; TUNEL+: 29.1±3.9), compared with controls (DFI: 7.1±0.9; TUNEL+: 14.2±1.2). Similarly, both groups of patients had significantly higher (p <0.01) levels of ROS. TAC levels did not differ between control and patient groups, suggesting that the DNA damage occurs before spermiation. Conclusions: Sperm DNA damage is significantly increased in men with idiopathic oligozoospermia and in cryptorchid subjects. The finding of increased ROS levels may indicate that seminal oxidative stress may be involved in the pathogenesis of sperm DNA damage in these patients.

Meckel-Gruber syndrome.

Meckel- Gruber syndrome is a rare lethal, autosomal disorder. It has been linked to chromosome 17. It consists of a triad of occipital meningoencephalocoele, large polycystic kidneys and post-axial polydactyly. Death is mainly due to pulmonary hypoplasia. We report this rare case which presented with many associated defects.

The CAG repeat within the androgen receptor gene and its relationship to cryptorchidism

PURPOSE: We examined the significance of the CAG repeat polymorphism in the pathogenesis of cryptorchidism. MATERIALS AND METHODS: Genomic deoxyribonucleic acid (DNA) was extracted from blood samples from 42 cryptorchid boys and from 31 non-cryptorchid control subjects. In the cryptorchid group, 7 had bilateral cryptorchidism and 6 had patent processus vaginalis in the contralateral side. To determine the number of CAG repeats, the DNA was amplified by polymerase chain reaction and sequenced. RESULTS: The mean CAG repeat length in the AR gene was 22.5 (range 16 to 28) in patients and 21.5 (range 17 to 26) in controls (non-significant). Patients with bilateral cryptorchidism had a mean length of 24.3 (range 21 to 26) and patients with unilateral cryptorchidism and patent processus vaginalis in the contra lateral side had a mean of 25.2 (range 21 to 28), which was statistically different from controls (p = 0.015 and p = 0.005 respectively). CONCLUSION: CAG repeat length of the AR gene does not seem to play a major role in patients with unilateral cryptorchidism. However, in patients with bilateral undescended testis, a less functional androgen receptor through a longer polyglutamine chain may have a role in its pathogenesis. In the same way, patients with unilateral cryptorchidism a contralateral patent processus vaginalis have longer CAG repeats that might be responsible for a slower testicular descent and incomplete closure of the processus vaginalis.

Síndrome de persistencia del conducto de Müller: presentación de un caso / Müller duct persistence syndrome: a case presentation

La diferenciación sexual masculino normal depende por lo menos de dos factores, testosterona y factor inhibidor mülleriano. La ausencia de este último produce una forma rara de pseudohermafroditismo masculino, el síndrome de persistencia del conducto de Müller, o hernia uterina inguinal. Se presenta el caso de un individuo fenotípicamente masculino, sometido a exploración quirúrgica por criptoquirdia bilateral, encontrando útero, trompas de falopio y ambos testículos. Se realizó extirpación de los remanentes müllerianos, orquidectomía derecha y orquidopexia izquierda. Se realiza una revisión de la literatura acerca de la etiología, presentación clínica, diagnóstico y tratamiento de este padecimiento

La histología en la criptorquidia / Histology in cryptorchism

En la actualidad no es posible encontrar una causa única demostrada de criptorquidea. Probablemente existe diversas causas, ya que algunos pacientes tienen como etiología una causa mecánica bien probada, en tanto que otras pueden explicarse mejor sobre bases genéticas, y otras más en endocrinas, ya sea por defecto o por exceso. Es muy dificil explicar los casos de criptorquidea unilateral sobre bases genéticas o endocrinas.

Asociación de criptorquidismo con nefritis hereditaria: estudio de tres generaciones de una familia puertorriqueña / Cryptorchidism associated with hereditary nephritis: a 3-generation study in a Puerto Rican family

Veintitrés miembros de una familia afectada por nefritis familiar fueron estudiados a lo largo de tres generaciones. La incidencia de manifestaciones auditivas, oculares y hematológicas fue baja. Se encontró que cuatro de los pacientes del sexo masculino con nefritis también presentaron criptorquidismo. En este reporte documentamos la ocurrencia no previamente registrada de criptorquidismo en asociación con la enfermedad de Alport. Se describen las características de la enfermedad en esta familia y se ofrece un repaso de la literatura sobre el tema

The A'-d ridge count in Ullrich-Turner syndrome: study in a large sample

Determinamos o valor da contagem de linhas A'-d numa constituída por 108 pacientes com síndrome de Ullrich-Turner (UTS), 28 mulheres com amenorréia primária e cariótipo normal e 111 controles femininos e 50 controles masculinos. O valor da contagem de linhas A'-d é significativamente maior nas pacientes com UTS que nos demais grupos, os quais por sua vez näo diferem entre si. Confirmamos, assim, a utilidade da contagem A'-d para o diagnóstico da UTS, apesar de a freqüência de classificaçöes errôneas no diagnóstico feito baseado apenas nessa contagem ser de 23%. Verificamos também que näo existem diferenças na contagem A'-d nas variantes citogenéticas de síndrome de UT bem como näo existe correlaçäo entre a contagem A'-d e afreqüência de células 45,X em casos de mosaicismo cromossômico 45,X/46,XX. Näo foi observado aumento na contagem A'-d em mulheres com amenorréia primária e cariótipo normal