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*

OBJECTIVES: To investigate the value of weight growth velocity, calculated using the Patel exponential model and the Z-score change method, in predicting the neurological and physical development outcomes of preterm infants with a gestational age of <30 weeks in the long term. METHODS: A retrospective study was conducted involving preterm infants with a gestational age of <30 weeks who were hospitalized and treated in the Department of Neonatology at Tongji Hospital, Huazhong University of Science and Technology, from January 2017 to June 2022, and were followed up at the outpatient service more than 18 months of age. The preterm infants were divided into high and low rate groups based on the two calculation methods, and the two methods were compared regarding their predictive value for neurological and physical development outcomes in the long term. RESULTS: The average age of the last follow-up was (23.0±3.6) months. For neurological development, according to the Patel exponential model, the low rate group exhibited a significantly higher abnormal rate in the fine motor domain compared to the high rate group (P<0.05). Using the Z-score change method, the low rate group had significantly higher abnormal rates in both gross motor and fine motor domains, and significantly lower developmental quotients for gross motor, fine motor, and adaptive behavior domains compared to the high rate group (P<0.05). For physical development, there were no significant differences in body length, body weight, head circumference, or the incidence rate of growth restriction between the low rate and high rate groups identified by either method (P>0.05). CONCLUSIONS Weight growth velocity calculated using the Z-score change method is more effective in predicting long-term neurological outcomes in preterm infants, while weight growth velocity derived from both methods shows no significant association with long-term physical development outcomes.
Humans ; Infant, Premature/growth & development* ; Retrospective Studies ; Infant, Newborn ; Child Development ; Male ; Female ; Body Weight ; Infant ; Nervous System/growth & development*

The patient, assigned female at birth and aged 1 year and 7 months, presented with clinical manifestations of 46,XY disorders of sex development. The external genitalia exhibited a severely undermasculinized phenotype. Laboratory tests and gonadal biopsy indicated poor Leydig cell function and good Sertoli cell function. Genetic testing revealed compound heterozygous mutations of c.867-2A>C and c.547G>A (p.G183R) in the LHCGR gene. The patient was ultimately diagnosed with type II Leydig cell hypoplasia. Type II Leydig cell hypoplasia presents a broad spectrum of clinical phenotypes, characterized by a lack of parallel function between Leydig cells and Sertoli cells, and significant individual variability in spermatogenesis and gender assignment. This condition should be considered when there is poor Leydig cell function but good development of Wolffian duct derivatives.
Female ; Humans ; Infant ; Disorder of Sex Development, 46,XY/genetics* ; Leydig Cells/pathology* ; Mutation ; Receptors, LH/genetics* ; Testis/abnormalities*

OBJECTIVES: To summarize the clinical manifestations and genetic characteristics of creatine deficiency syndrome (CDS) caused by GAMT gene mutations. METHODS: A retrospective analysis was conducted on the clinical and genetic data of two children diagnosed with GAMT deficiency-type CDS at the Children's Medical Center of Xiangya Hospital, Central South University, from December 2020 to December 2024. RESULTS: The two patients presented with symptoms in infancy, and both had compound heterozygous mutations in the GAMT gene. Case 1 exhibited seizures and intellectual disability, while Case 2 had intellectual disability and attention-deficit hyperactivity disorder. Magnetic resonance spectroscopy of cranial MRI in both patients indicated reduced creatine peaks. After creatine treatment, seizures in Case 1 were controlled, but both patients continued to experience intellectual disabilities and behavioral issues. As of December 2024, a total of 21 cases have been reported in China (including this study), and 115 cases have been reported abroad. All patients exhibited developmental delay or intellectual disabilities, with 66.9% (91/136) experiencing seizures, 33.8% (46/136) presenting with motor disorders, and 36.8% (50/136) having behavioral problems. Seventy-five percent (102/136) of patients received creatine treatment, leading to significant improvements in seizures and motor disorders, although cognitive improvement was not substantial. CONCLUSIONS GAMT deficiency-type CDS is rare and presents with nonspecific clinical features. Timely diagnosis facilitates targeted treatment, which can partially improve prognosis.
Child ; Female ; Humans ; Male ; Creatine/deficiency* ; Guanidinoacetate N-Methyltransferase/deficiency* ; Intellectual Disability/genetics* ; Mutation ; Retrospective Studies ; Rhabdomyolysis/genetics* ; Language Development Disorders ; Movement Disorders/congenital*

OBJECTIVES: To study the effects of early respiratory training combined with swallowing function training on physical development and neurodevelopment at a corrected gestational age of 6 months in infants with bronchopulmonary dysplasia (BPD). METHODS: A total of 69 BPD infants who could not be fed completely orally were prospectively selected from the Department of Neonatology of Hunan Children's Hospital between January 2018 and January 2021. Based on a random number table, the infants were divided into a conventional group (35 cases) and a training group (34 cases) (with 8 cases lost to follow-up; the final follow-up included 31 cases in the training group and 30 cases in the conventional group). Both groups received routine clinical treatment and care, while the training group additionally received respiratory and swallowing function training until the infants could independently feed orally. The weight, length, Gesell Developmental Schedule (GDS) results, readmission rate, and multiple readmission rate (two or more admissions) were compared between the two groups at a corrected age of 6 months. RESULTS: At corrected gestational age of 6 months, the training group had higher weight, length, and GDS scores in personal-social, language, gross motor, fine motor, and adaptive development compared to the conventional group (P<0.05). The readmission rate and multiple readmission rate were lower in the training group compared to the conventional group (P<0.05). CONCLUSIONS Early respiratory training combined with swallowing function training for BPD infants in a neonatal intensive care unit setting helps improve physical and neurological development and reduces the readmission rate.
Humans ; Bronchopulmonary Dysplasia/physiopathology* ; Prospective Studies ; Male ; Female ; Infant ; Deglutition/physiology* ; Gestational Age ; Infant, Newborn ; Breathing Exercises ; Child Development

This paper provides an interpretation of the "Expert consensus on the diagnosis and treatment of neonatal hyperammonemia" published in the May 2023 issue of the Chinese Journal of Contemporary Pediatrics. The interpretation focuses on key aspects such as the neurotoxicity of ammonia, classification of etiologies, diagnosis, nutritional management, and pharmacological treatment. The aim is to enhance awareness about ammonia testing and emphasize that treatment should not be delayed while awaiting etiological investigation, thereby advancing the diagnosis and treatment of neonatal hyperammonemia.
Humans ; Infant, Newborn ; Hyperammonemia/etiology* ; Consensus Development Conferences as Topic

OBJECTIVES: To investigate the growth parameters of children with phenylketonuria and assess the impact of a phenylalanine-restricted diet on their physical development. METHODS: The study involved 39 children diagnosed with phenylketonuria through newborn screening at the Central Child Teaching Hospital, Baghdad, Iraq. Data were collected during scheduled monthly check-ups, including phenylalanine levels, diet compliance, and anthropometric measurements. The children were divided into two groups based on their phenylalanine levels during the 3-year follow-up period: well-controlled group (average phenylalanine level of less than 360 μmol/L, with no single reading exceeding 600 μmol/L; n=14) and poorly-controlled group (one or more phenylalanine readings above 600 μmol/L during the follow-up period; n=25). RESULTS: The mean height readings for all time points (at birth and 3, 6, 9, 12, 15, 18, 21, 24 and 36 months of age) were higher in the well-controlled group than the poorly-controlled group, however, only at 3 months of age the difference was statistically significant. Height Z-scores revealed a clearer pattern: although the poorly-controlled group had higher height Z-scores at birth (P=0.001), the well-controlled group showed significantly higher height Z-scores at 3, 6, 12, 15, 18, 24, and 36 months (P<0.05). The well-controlled group exhibited significantly higher mean weight measurements compared to the poorly-controlled group at 3, 6, 9, 15, 18 months and 21 months (P<0.05). From 6 to 36 months, the well-controlled group consistently had significantly higher weight Z-scores than the poorly-controlled group (P<0.05). The well-controlled group showed more favorable height and weight Z-score distributions at 36 months of age compared to the poorly-controlled group, but the differences were not statistically significant (P>0.05). Both groups had height and weight Z-scores within the normal range at 36 months of age. CONCLUSIONS The children with phenylketonuria who receive good dietary control show better improvements in growth parameters compared to those with poor dietary control, however, both groups maintain height and weight Z-scores within the normal range, indicating generally adequate physical development across the cohort.
Humans ; Phenylketonurias/diet therapy* ; Male ; Female ; Child, Preschool ; Infant ; Body Height ; Infant, Newborn ; Child Development ; Phenylalanine/blood*

The patient was a boy aged 1 year and 9 months who presented with 46,XY disorder of sex development (DSD), with severe undermasculinization of the external genitalia. Laboratory tests and ultrasound examinations showed normal functions of Leydig cells and Sertoli cells in the testes. Genetic testing revealed a novel pathogenic heterozygous variant, c.1186dupA (p.T396Nfs*17), in the PPP1R12A gene. Thirteen cases of PPP1R12A gene variants have been reported previously. These variants may cause isolated involvement of the genitourinary or neurological systems, or affect other systems/organs including the digestive tract, eyes, heart, etc. Patients with DSD typically present with a 46,XY karyotype and variable degrees of undermasculinization involving the external genitalia, gonads, and reproductive tract. This article reports a child with 46,XY DSD accompanied by growth retardation caused by a heterozygous variant in the PPP1R12A gene, which expands the clinical disease spectrum associated with PPP1R12A gene variants.
Humans ; Male ; Infant ; Disorder of Sex Development, 46,XY/etiology* ; Protein Phosphatase 1/genetics*

OBJECTIVES: To investigate the dynamic changes in serum microRNA-15b (miR-15b) and vascular endothelial growth factor (VEGF) in preterm infants with mild or moderate-to-severe bronchopulmonary dysplasia (BPD), as well as their value in assessing short-term neurodevelopment. METHODS: A retrospective analysis was conducted on the medical data of 156 preterm infants with BPD who were admitted to the neonatal intensive care unit from January 2020 to February 2023. According to the severity of BPD, they were divided into a mild group (n=88) and a moderate-to-severe group (n=68). Serum levels of miR-15b and VEGF were measured on postnatal days 1, 7, 14, and 28. Repeated measures analysis of variance was used to assess the dynamic changes in serum levels of miR-15b and VEGF. The mediating effect of VEGF between miR-15b and short-term neurological development was tested and analyzed using the stepwise regression method and the Bootstrap method. Logistic regression analysis was used to identify factors influencing adverse neurodevelopmental outcomes. RESULTS: In the mild group, there was a significant reduction in the serum level of miR-15b and a significant increase in VEGF over time (P<0.05), while in the moderate-to-severe group, there was a significant increase in miR-15b and a significant reduction in VEGF over time (P<0.05). Serum miR-15b and VEGF levels were important factors influencing neurodevelopmental outcomes, showing independent correlations (P<0.001). The mediating effect analysis indicated that miR-15b indirectly affected short-term neurodevelopment by inhibiting VEGF expression [indirect effect: -0.705 (95%CI: -1.178 to -0.372)], with the indirect effect accounting for 54.36% of the total effect. CONCLUSIONS There are different changing trends in serum levels of miR-15b and VEGF in preterm infants with mild and moderate-to-severe BPD. miR-15b primarily influences neurodevelopment through VEGF.
Humans ; Bronchopulmonary Dysplasia/physiopathology* ; MicroRNAs/blood* ; Vascular Endothelial Growth Factor A/blood* ; Infant, Newborn ; Infant, Premature/blood* ; Female ; Male ; Retrospective Studies ; Child Development ; Nervous System/growth & development*

OBJECTIVES: To explore the status and risk factors of neuropsychological development in small for gestational age (SGA) infants at corrected 12-24 months of age. METHODS: Clinical data were retrospectively collected for 754 SGA infants at corrected ages 12-24 months in Shenzhen Bao'an Women and Children's Hospital between April 2018 and December 2023. Developmental quotient (DQ) levels were analyzed. According to the presence of global developmental delay (GDD), participants were divided into a GDD group (71 cases) and a control group (683 cases), and the incidence and influencing factors of GDD were investigated. RESULTS: In the high-risk preterm SGA group, the total DQ and DQ in all domains were lower than in the full-term SGA group (P<0.017). The overall incidence of GDD was 9.4% (71/754) and increased with decreasing gestational age (P<0.017). Compared with the control group, the GDD group had higher proportions of males; low-risk and high-risk preterm birth; mothers with less than a bachelor's degree; multiple birth; neonatal hypoglycemia; neonatal pneumonia; neonatal respiratory distress syndrome; bronchopulmonary dysplasia; and, at corrected 12-24 months, low body weight, growth retardation, and microcephaly. The length of neonatal hospital stay was longer in the GDD group than in the control group (P<0.05). The weight-for-age Z score, length-for-age Z score, and head circumference-for-age Z score at birth and at corrected 12-24 months were lower in the GDD group than in the control group (P<0.05). Multivariable logistic regression showed that male sex and maternal education below a bachelor's degree were independent risk factors for GDD in SGA infants (P<0.05). CONCLUSIONS Neuropsychological development in preterm SGA infants is comparatively delayed; male SGA infants born to mothers with less than a bachelor's degree should receive priority attention.
Humans ; Female ; Male ; Infant, Small for Gestational Age/psychology* ; Risk Factors ; Infant ; Retrospective Studies ; Child Development ; Developmental Disabilities/epidemiology* ; Infant, Newborn ; Child, Preschool