OBJECTIVE: To summarize the clinical and genetic characteristics of a child with 46,XX Ovotesticular disorder of sex development (46,XX OTDSD) due to copy number variation of SOX3 gene. METHODS: A 46,XX male patient presented at the Capital Center for Children's Health, Capital Medical University in November 2024 was selected as the study subject. Clinical data of the child was collected. Peripheral blood samples were taken from the child and his parents and subjected to trio whole-genome sequencing. Skewed X-chromosome inactivation was tested in the child and his mother. A literature review was carried out on 46,XX males associated with mutations of the SOX3 gene. This study was approved by the Medical Ethics Committee of the Hospital (Ethics No.: SHERLL2025056). RESULTS: The 10-year-old boy presented with hypospadias and cryptorchidism at birth. Chromosome analysis at one year and a half revealed a 46,XX karyotype. Gonadal biopsy showed testicular tissue, while ultrasound at the age of 10 detected ovotesticular tissue. Whole-genome sequencing identified a 660 kb duplication in the Xq27.1 region, which was derived from his mother. X-chromosome inactivation testing showed random inactivation in the child and mild non-random inactivation in the mother. Literature review has found 11 publications involving 15 patients (including our case), among whom 14 had a male social gender. They had primarily presented with hypospadias at birth but had no significant endocrine abnormalities. Most patients had experienced testicular failure after puberty. SOX3 related 46,XX males are mainly caused by de novo duplications, although a few maternal carriers had been discovered. CONCLUSION Duplication of the SOX3 gene probably underlay the pathogenesis is this 46,XX male. Individuals with 46,XX SRY negative male phenotypes should be routinely screened for SOX3 gene variants. Structural variations of the SOX3 gene can lead to complete or partial sex reversal in 46,XX individuals with minimal impact on intellectual and motor development, as well as other endocrine hormones.
Child ; Humans ; Male ; 46, XX Disorders of Sex Development/genetics* ; DNA Copy Number Variations ; Gene Duplication ; Phenotype ; SOXB1 Transcription Factors/genetics*

Objective Summarize the endocrine characteristics of 5 children with Wiedemann-Steiner syndrome(WDSTS)to enhance the early recognition capability of clinicians for this condition.Methods A retrospective analysis of the medical history,clinical manifestations,genetic testing,and treatment of 5 children with Wiedemann-Steiner syndrome treated in the endocrinology department of capital center for children's health,capital medical university from October 2020 to December 2024,summarizing the clinical characteristics of the disease.Results Among the 5 cases of WDSTS,there were 2 males and 3 females,with ages ranging from 1.9 to 10 years at the time of diagnosis.Cases 1 and 3 were born prematurely,and cases 1,2 and 5 were diagnosed as small for gestational age(SGA)infants.All 5 children exhibited distinctive facial features,hirsutism,sacral dimple,developmental delay,and adenoid hypertrophy,premature tooth replacement,feeding difficulties,and a high incidence of urinary system abnormalities.Four children complained of slow growth.Cases 1 and 4 were diagnosed with short stature.Cases 3 and 5 had normal height but were slightly shorter with advanced bone age.Case 5 also experienced early puberty.Case 2 was diagnosed with premature adrenarche and idiopathic central precocious puberty due to the presence of pubic hair and breast enlargement.Cases 1 and 3 were treated with recombinant human growth hormone(rhGH),which resulted in significant height growth(approximately 10 cm/year).However,treatment was discontinued in Case 1 due to a significant advancement in bone age.Conclusions WDSTS should be considered in patients presenting with short stature,distinctive facial features,hirsutism,developmental delay,and multiple system deformities.While rhGH treatment can help improve height in these patients,the potential for accelerated bone age maturation during treatment requires careful monitoring.

Objective:To analyze the clinical and genetic characteristics of children diagnosed with Noonan-syndrome associated with loose anagen hair (NS-LAH).Methods:A retrospective analysis was conducted on the clinical data of 5 children diagnosed with NS-LAH by the Endocrinology Department of the Capital Institute of Pediatrics from January 2018 to June 2024. This analysis encompassed the patients′ demographic information, clinical manifestations, distinguishing features, treatment regimens, and prognostic outcomes to elucidate their clinical characteristics. Additionally, whole-exome sequencing and Sanger sequencing were utilized to investigate the genetic etiology within the families, and the identified variations were interpreted according to the guidelines of the American College of Medical Genetics and Genomics.Results:Among the 5 NS-LAH patients, there were 3 boys and 2 girls, with ages at diagnosis ranging from 2.3 to 7.7 years old. All patients presented with short stature as a primary complaint. Birth histories were generally unremarkable, though case 2 and 5 of macrosomia were noted. In addition to the characteristic facial features of Noonan syndrome, short stature, and varying degrees of intellectual and motor developmental delay, all 5 patients exhibited sparse hair that was easily shed, as well as enlarged head circumferences. Four patients showed structural cardiac abnormalities, which included a case of hypertrophic cardiomyopathy, 2 cases of atrial septal defect, and 1 case of patent foramen ovale. Genetic analysis revealed heterozygous missense variantion in SHOC2 gene in 4 patients, comprising 3 cases with c.4A>G (p.S2G) and one case with c.519G>C (p.M173I). Additionally, one patient was found to have a heterozygous missense variantion c.146C>G (p.P49R) in PPP1CB gene. Three children were diagnosed with growth hormone deficiency and treated with growth hormone for 1.7, 2.7 and 0.5 years. This resulted in significant improvements in height, with annual increases of 11.8, 8.4 and 13.0 cm, respectively. Among the 4 patients with SHOC2 variantions, 2 developed systemic lupus erythematosus and 1 exhibited symptoms of arthritis.Conclusions:Growth failure is the primary complaint in patients with NS-LAH. Key characteristic findings include enlarged head circumference and sparse, loose hair. Growth hormone deficiency is commonly associated with NS-LAH, and growth hormone therapy is generally effective. Furthermore, patients carrying the classic variantion in SHOC2 (c.4A>G) may have an increased risk of developing autoimmune diseases.

Objective:To analyze the clinical characteristics of familial hypercholesterolemia (FH) in children and provide a basis for clinical diagnosis and individualized treatment.Methods:Case series study. Clinical data of 24 children with FH, who were admitted to the Department of Endocrinology in Capital Center for Children′s Health, Capital Medical University, from January 2018 to January 2025, were analyzed. Follow-ups were performed every 3-6 months and ended in January 2025. According to the results of genetic testing, the children were divided into homozygous familial hypercholesterolemia (HoFH) group and heterozygous familial hypercholesterolemia (HeFH) group. The blood lipid levels of different subtypes, the efficacy of different treatments, and clinical outcomes were compared by Mann-Whitney U test. Results:The 24 children were from 17 families, including 14 males and 10 females, with a diagnostic age of 5.0 (3.0, 9.5) years. Genetic testing results showed that 22 cases (92%) had LDLR gene variants and 2 cases (8%) had APOB gene variants, all of which were inherited from parents. There were 5 cases (21%) of HoFH and 19 cases (79%) of HeFH, and 4 previously unreported new loci were identified. There were 6 children (25%) presented with xanthomas, including 5 cases of HoFH and 1 case of HeFH. The level of low-density lipoprotein cholesterol (LDL-C) in the HoFH group was significantly higher than that in the HeFH group ( P<0.05). Regarding treatment, 11 children received dietary control without taking medicine, 6 were treated with statins, 3 with ezetimibe, and 3 with statins combined with ezetimibe, and 1 underwent liver transplantation. None of the children receiving only dietary control achieved the target LDL-C level (<3.49 mmol/L or a reduction of >50%), and there was no statistically significant difference in LDL-C before and after dietary control ( P=0.158). After treatment with statins and (or) ezetimibe, LDL-C decreased in 12 children ( P<0.05); among them, 6 cases (all HeFH) reached the target LDL-C level. There was no statistically difference in LDL-C levels before and after treatment with atorvastatin and ezetimibe in 5 HoFH children( P>0.05). One HoFH child had LDL-C reduced to the normal range after liver transplantation. No serious adverse reactions were observed in all children during drug treatment. In the detection of vascular-related complications among 12 HeFH children, only 1 child had a slight thickening of the bilateral carotid intima-media, while no abnormalities were found in the others. Conclusions:Xanthoma is a characteristic manifestation of FH, but its incidence is relatively low in HeFH children. Family history and genetic testing are key evidences for the diagnosis of FH. Dietary control has limited efficacy in children with FH, and drug treatment should be initiated as early as possible. LDL-C levels in HoFH children are more difficult to control, if drug treatment shows poor efficacy, liver transplantation may be a better option.

Objective:To analyze the clinical and genetic characteristics of children diagnosed with Noonan-syndrome associated with loose anagen hair (NS-LAH).Methods:A retrospective analysis was conducted on the clinical data of 5 children diagnosed with NS-LAH by the Endocrinology Department of the Capital Institute of Pediatrics from January 2018 to June 2024. This analysis encompassed the patients′ demographic information, clinical manifestations, distinguishing features, treatment regimens, and prognostic outcomes to elucidate their clinical characteristics. Additionally, whole-exome sequencing and Sanger sequencing were utilized to investigate the genetic etiology within the families, and the identified variations were interpreted according to the guidelines of the American College of Medical Genetics and Genomics.Results:Among the 5 NS-LAH patients, there were 3 boys and 2 girls, with ages at diagnosis ranging from 2.3 to 7.7 years old. All patients presented with short stature as a primary complaint. Birth histories were generally unremarkable, though case 2 and 5 of macrosomia were noted. In addition to the characteristic facial features of Noonan syndrome, short stature, and varying degrees of intellectual and motor developmental delay, all 5 patients exhibited sparse hair that was easily shed, as well as enlarged head circumferences. Four patients showed structural cardiac abnormalities, which included a case of hypertrophic cardiomyopathy, 2 cases of atrial septal defect, and 1 case of patent foramen ovale. Genetic analysis revealed heterozygous missense variantion in SHOC2 gene in 4 patients, comprising 3 cases with c.4A>G (p.S2G) and one case with c.519G>C (p.M173I). Additionally, one patient was found to have a heterozygous missense variantion c.146C>G (p.P49R) in PPP1CB gene. Three children were diagnosed with growth hormone deficiency and treated with growth hormone for 1.7, 2.7 and 0.5 years. This resulted in significant improvements in height, with annual increases of 11.8, 8.4 and 13.0 cm, respectively. Among the 4 patients with SHOC2 variantions, 2 developed systemic lupus erythematosus and 1 exhibited symptoms of arthritis.Conclusions:Growth failure is the primary complaint in patients with NS-LAH. Key characteristic findings include enlarged head circumference and sparse, loose hair. Growth hormone deficiency is commonly associated with NS-LAH, and growth hormone therapy is generally effective. Furthermore, patients carrying the classic variantion in SHOC2 (c.4A>G) may have an increased risk of developing autoimmune diseases.

Objective:To analyze the clinical characteristics of familial hypercholesterolemia (FH) in children and provide a basis for clinical diagnosis and individualized treatment.Methods:Case series study. Clinical data of 24 children with FH, who were admitted to the Department of Endocrinology in Capital Center for Children′s Health, Capital Medical University, from January 2018 to January 2025, were analyzed. Follow-ups were performed every 3-6 months and ended in January 2025. According to the results of genetic testing, the children were divided into homozygous familial hypercholesterolemia (HoFH) group and heterozygous familial hypercholesterolemia (HeFH) group. The blood lipid levels of different subtypes, the efficacy of different treatments, and clinical outcomes were compared by Mann-Whitney U test. Results:The 24 children were from 17 families, including 14 males and 10 females, with a diagnostic age of 5.0 (3.0, 9.5) years. Genetic testing results showed that 22 cases (92%) had LDLR gene variants and 2 cases (8%) had APOB gene variants, all of which were inherited from parents. There were 5 cases (21%) of HoFH and 19 cases (79%) of HeFH, and 4 previously unreported new loci were identified. There were 6 children (25%) presented with xanthomas, including 5 cases of HoFH and 1 case of HeFH. The level of low-density lipoprotein cholesterol (LDL-C) in the HoFH group was significantly higher than that in the HeFH group ( P<0.05). Regarding treatment, 11 children received dietary control without taking medicine, 6 were treated with statins, 3 with ezetimibe, and 3 with statins combined with ezetimibe, and 1 underwent liver transplantation. None of the children receiving only dietary control achieved the target LDL-C level (<3.49 mmol/L or a reduction of >50%), and there was no statistically significant difference in LDL-C before and after dietary control ( P=0.158). After treatment with statins and (or) ezetimibe, LDL-C decreased in 12 children ( P<0.05); among them, 6 cases (all HeFH) reached the target LDL-C level. There was no statistically difference in LDL-C levels before and after treatment with atorvastatin and ezetimibe in 5 HoFH children( P>0.05). One HoFH child had LDL-C reduced to the normal range after liver transplantation. No serious adverse reactions were observed in all children during drug treatment. In the detection of vascular-related complications among 12 HeFH children, only 1 child had a slight thickening of the bilateral carotid intima-media, while no abnormalities were found in the others. Conclusions:Xanthoma is a characteristic manifestation of FH, but its incidence is relatively low in HeFH children. Family history and genetic testing are key evidences for the diagnosis of FH. Dietary control has limited efficacy in children with FH, and drug treatment should be initiated as early as possible. LDL-C levels in HoFH children are more difficult to control, if drug treatment shows poor efficacy, liver transplantation may be a better option.

OBJECTIVE: To analyze the clinical and genetic characteristics of a Chinese pedigree affected with congenital Isolated growth hormone deficiency (IGHD). METHODS: A pedigree presenting with Pituitary stalk interruption syndrome (PSIS) (including the proband, his two younger sisters and both parents) who had visited the Capital Institute of Pediatrics Affiliated to Capital Medical University in September 2020 was selected as the study subject. Clinical data were collected. Peripheral blood samples were collected from the proband and his family members. Following the extraction of genomic DNA, whole-exome sequencing (WES) was carried out, and candidate variants were validated by Sanger sequencing. The pathogenicity of the candidate variants was classified based on guidelines from the American College of Medical Genetics and Genomics (ACMG). This study was approved by the Medical Ethics Committee of the Institute Pediatrics of Capital Medical University (Ethics No.: SHERLL2025033). RESULTS: The proband and one younger sister (Ⅱ3) presented with growth retardation, short stature, and a doll-like facies. Another younger sister (Ⅱ2) and both parents had normal heights and appearance. Sanger sequencing confirmed that the proband and his younger sister (Ⅱ3) both harbored compound heterozygous variants of the GHRHR gene, namely c.776C>A (p.T259K) and c.1166G>A (p.R389Q). The other younger sister (Ⅱ2) and the parents were heterozygous carriers. The c.1166G>A (p.R389Q) variant was unreported previously. Based on the guidelines from the ACMG, it was classified as variant of uncertain significance (PM2_Supporting+BP4). Bioinformatics analysis indicated a deleterious effect on the protein function. CONCLUSION Variants of the GHRHR gene probably underlay the pathogenesis of IGHD in this pedigree. Above finding has provided a basis for the clinical diagnosis and genetic counseling for this family.
Child ; Female ; Humans ; Male ; China ; Dwarfism, Pituitary/genetics* ; Exome Sequencing ; Human Growth Hormone/deficiency* ; Mutation ; Pedigree ; Receptors, Neuropeptide/genetics* ; Receptors, Pituitary Hormone-Regulating Hormone/genetics* ; East Asian People/genetics*

Objective Summarize the endocrine characteristics of 5 children with Wiedemann-Steiner syndrome(WDSTS)to enhance the early recognition capability of clinicians for this condition.Methods A retrospective analysis of the medical history,clinical manifestations,genetic testing,and treatment of 5 children with Wiedemann-Steiner syndrome treated in the endocrinology department of capital center for children's health,capital medical university from October 2020 to December 2024,summarizing the clinical characteristics of the disease.Results Among the 5 cases of WDSTS,there were 2 males and 3 females,with ages ranging from 1.9 to 10 years at the time of diagnosis.Cases 1 and 3 were born prematurely,and cases 1,2 and 5 were diagnosed as small for gestational age(SGA)infants.All 5 children exhibited distinctive facial features,hirsutism,sacral dimple,developmental delay,and adenoid hypertrophy,premature tooth replacement,feeding difficulties,and a high incidence of urinary system abnormalities.Four children complained of slow growth.Cases 1 and 4 were diagnosed with short stature.Cases 3 and 5 had normal height but were slightly shorter with advanced bone age.Case 5 also experienced early puberty.Case 2 was diagnosed with premature adrenarche and idiopathic central precocious puberty due to the presence of pubic hair and breast enlargement.Cases 1 and 3 were treated with recombinant human growth hormone(rhGH),which resulted in significant height growth(approximately 10 cm/year).However,treatment was discontinued in Case 1 due to a significant advancement in bone age.Conclusions WDSTS should be considered in patients presenting with short stature,distinctive facial features,hirsutism,developmental delay,and multiple system deformities.While rhGH treatment can help improve height in these patients,the potential for accelerated bone age maturation during treatment requires careful monitoring.

To analyze the clinical characteristics and follow-up data of Chinese patients with calcium-sensing receptor (CaSR) signaling pathway related hypercalcemia. A retrospective analysis was conducted on six children with hypercalcemia admitted to Department of Endocrinology, Children′s Hospital Affiliated to Capital Institute of Pediatrics from July 2017 to November 2022. Summarized the clinical and pathogenic variants, as well as follow-up data. The results showed that 3 were female and 3 were male of the 6 cases, aged from 2 months to 8 years at the consultation. The clinical symptoms varied from asymptomatic hypercalcemia to vomiting, dehydration, and growth retardation,as well as epilepsy and intellectual disability. Except for 1 case, which showed a significant increase in blood calcium (4.63 mmol/L), the blood calcium of other cases ranged from 2.98 to 3.17 mmol/L. Among the 6 patients, 5 had elevated parathyroid hormone, and 1 was normal. Three cases showed a significant decrease in 24-hour urinary calcium to creatinine ratio. Whole exome sequencing revealed that one patient had compound heterozygous variants and four had a heterozygous variants of CaSR gene, one patient had a heterozygous variant of AP2S1 gene. 1 case underwent total parathyroidectomy, followed by calcium supplementation, 3 cases received salmon calcitonin treatment, and 2 cases accepted low calcium diet, blood calcium levels were all controlled well. In conclusion, CaSR signaling pathway related hypercalcemia is rare. Gene detection is essential for children with hypercalcemia. Familial hypocalcemia hypercalcemia (FHH) can be effectively treated with salmon calcitonin.

Objective To construct a theoretical model of venous thromboembolism(VTE)risk perception in pregnant women,so as to provide a scientific basis for promoting pregnant women to form a correct risk perception of VTE and actively take preventive behaviors.Methods A qualitative research approach guided by the procedural grounded theoiy was adopted.Data were collected by a semi-structured deep interview on 18 pregnant women who received prenatal examination in the outpatient department of a tertiary A obstetrics and gynecology hospital in Nanjing from June to July 2023,and the data were analyzed by three-level coding and continuous comparison method.Results The VTE risk perception of pregnant women was affected by 6 factors including social coupling system,self health status,life behavior habits,knowledge on disease,compliance behavior and emotional stimulation.Pregnant women perceived VTE risk from 3 aspects:threats to maternal and child safety,increased family economic burden and increased time cost,impact on social roles.Thus,3 health behavior decisions were formed,including taking preventive behaviors,overcoming implementation barriers,and seeking knowledge behaviors,in order to reduce their own risk of VTE,and prevent the occurrence of VTE.Conclusion The theoretical model of VTE risk perception of pregnant women can guide medical staff to comprehensively consider the influencing factors of VTE risk perception of pregnant women,optimize the form and content of VTE health education,give pregnant women individualized and sustainable VTE prevention guidance,and strengthen pregnant women's perception of VTE risk and the benefits of preventive behavior,so as to actively take the correct health behavior decisions.