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Objective:To analyze the clinical and genetic characteristics of congenital hypogonadotropic hypogonadism (CHH) in boys.Methods:Cross-sectional study.Clinical data, laboratory data and genetic results of boys who were genetically diagnosed with CHH at the Department of Endocrinology of Shenzhen Children′s Hospital from December 2019 to February 2023 were collected in this retrospective study.Their clinical manifestations, hormone levels and gene mutations were analyzed.The non-normal distribution was represented by the median.The rank sum test was used to compare the non-normal distribution data between the two groups.Results:A total of 27 boys were genetically diagnosed with CHH, with the age at first diagnosis ranging from 0.3 to 16.6 years old.All these children presented with micropenis (100%), of whom 16 were complicated with cryptorchidism (59.3%), 9 with microrchidia (33.3%), 7 with simple micropenis (25.9%), and no had simple cryptorchidism.Three children had cardiovascular dysplasia.The median of basal luteinizing hormone(LH) level was 0.09 IU/L, and 92.5%(25/27) of children had the basal LH level below 1.00 IU/L.The median of peak LH level after gonadotropin-releasing hormone(GnRH) stimulation was 1.42 IU/L, and 96.2%(26/27) of children had the peak LH level below 4.00 IU/L.The median of serum inhibin B was 41.15 μg/L, and the median of serum anti-Müllerian hormone(AMH) was 12.62 mg/L.The serum AMH level of children with cryptorchidism was significantly lower than that of children without cryptorchidism (10.02 mg/L vs.50.50 mg/L, P<0.05). A total of 12 gene mutations were detected in the 27 children, of which 1 was biallelic mutation.The most common gene mutations were in CHD7 and ANOS1 genes (7 children each, both accounting for 51.8%), followed by FGFR1 gene (3 children, 11.1%). After short-term treatment by GnRH pump or subcutaneous injection of recombinant human follicle stimulating hormone in 4 children, the levels of serum inhibin B and AMH increased significantly, and the testicular volume also increased. Conclusions:CHH is a congenital disease with different clinical manifestations at different ages.The main manifestations in childhood are micropenis and cryptorchidism, and some children have microrchidia.Its diagnosis in prepuberty is difficult, but genetic testing is of great significance for early diagnosis.
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To summarize the clinical manifestations of a case with 46, XY sex development disorder caused by myelin regulatory factor(MYRF) gene mutation and review the literature to deepen the specialists′ understanding of the clinical disease spectrum resulting from MYRF gene variations. The child had a female phenotype with mild masculinity, chromosome 46, XY, sex-determining region of Y gene(SRY gene) positive, laboratory tests were consistent with primary hypogonadism, ultrasound did not detect the gonads, but the residual reproductive tract was visible, and echocardiography suggested coarctation of the aorta, MYRF gene c. 2518C>T(p.R840*) heterozygous variant. The father did not carry this variant. The mother was untraceable, and genetic testing had not been completed. It was analyzed as pathogenic variation according to American College of Medical Genetics and Genomics(ACMG) guidelines. Sixteen cases of disorders of sex development caused by MYRF gene variation reported from 2018 to 2021 were reviewed, MYRF gene variants, 46, XY, and 46, XX individuals can be pathogenic, can affect the gonad and reproductive tract at the same time, and can also affect multiple systems. In this case, the patient presents with 46, XY sex development disorder due to MYRF gene mutation, accompanied by rare cardiovascular complications. When encountering 46, XY primary hypogonadism without well-developed Müllerian duct structures, this condition should be considered. Following confirmation, a comprehensive assessment of multi-organ function is necessary.
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Objective:To report embryonic testicular regression syndrome(ETRS) caused by DHX37 heterozygous variant for the first time in China and summarize the clinical manifestations of ETRS as to improve the understanding of doctors for this disease.Methods:The clinical data and whole exome sequencing results of five cases of ETRS from Shenzhen Children′s Hospital were collected. The reported cases of DHX37 heterozygous variant were reviewed.Results:Five patients with ETRS visited the doctors at the age of 2 months to 5 years and 5 months. Three patients raised as males came to hospital due to virilition and 2 female patients visited a doctor due to clitoral hypertrophy. No uterus was detected by ultrasound in all patients. The gonadal pathologies from 4 cases displayed no testicular tissue or gonadal dysgenesis, complicated with gonadoblastoma in one case. The genetic testing revealed that the heterozygous variant(c.923G>A, p. R308Q) in DHX37 was found in 2 cases, without variant in other 3 cases. According to the review, ETRS and 46, XY gonadal dysgenesis due to DHX37 herozygous variant was firstly reported in 2019. A total of 40 cases, including 21 cases of ETRS, presented with the virilition or female phenotype, with the disappearance of testicular tissue as the main pathologies. There is no report in China.Conclusion:The article summarized the clinical manifestations and whole exome sequencing results of 5 patients with ETRS, among which two cases were caused by DHX37 variants and one was complicated with gonadoblastoma.
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The clinical characteristics of a case of fetal alcohol syndrome (FAS) diagnosed by Shenzhen Children′s Hospital were summarized.The patient was 6 years and 4 months old, and admitted to the hospital because of her " slow growth of height for more than 6 years" . There was a history of alcohol exposure in the fetus.The infant was born with low body mass, and grew slowly in height and body mass after birth.She was diagnosed with FAS due to typical facial features of FAS, microcephalia, poor memory and narrative ability.The effect of alcohol exposure during pregnancy on fetus is permanent, and abstinence is the only way to prevent FAS.In this paper, the clinical characteristics of FAS were summarized and the literature was reviewed in order to improve the clinical understanding of the disease.
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Objective To discuss the expression and clinical significance of vascular endothelial growth factor (VEGF)-C and nm23-H1 in colorectal carcinoma.Methods Immunohistochemical staining was employed to determine the expression of VEGF-C and nm23-H1 in the carcinoma tissues of 120 cases with colorectal carcinoma and in the adjacent mucosal tissues of 55 cases as control,and analyzed their correlation with cliniopathological features and prognosis.Results The positive expression of VEGF-C in the carcinoma tissues was 71.7％ (86/120),significantly higher than that in the adjacent mucosal tissues [21.8 ％ (12/55)],and there was significant difference (x2 =35.186,P ＜ 0.01).The positive expression of nm23-H1 in the carcinoma tissues was 57.5％ (69/120),significantly lower than that in the adjacent mucosal tissues [90.9％ (50/55)],and there was significant difference (x2 =18.351,P ＜ 0.01).The expression of VEGF-C was significantly correlated with lymph node metastasis (P ＜ 0.05),and the expression of nm23-H 1was significantly correlated with lymph node metastasis and pathological type (P ＜0.01 or ＜0.05).The expression of VEGF-C and nm23-H1 did not show a significant correlation with gender,age,tumor size,tumor site and depth of invasion (P ＞ 0.05).Spearman correlation analysis showed that the expression of VEGF-C was negatively correlated with the expression of nm23-H 1 in colorectal carcinoma (r =-0.472,P ＜0.01).Conclusions The joint detection of VEGF-C and nm23-H1 expression is very promising in prediction of the prognosis of patients with colorectal carcinoma.However,whether it can be used as a marker in prognosis judgment need further investigation.