ObjectiveTo explore the ethical issues and coping strategies in the diagnosis and treatment of 46, XY disorders of sex development （46, XY DSD） under a multidisciplinary team （MDT） model， and to deepen the understanding of relevant ethical issues while accumulating experience. MethodsA retrospective collection was conducted on the data of children with 46, XY disorders of sex development under a single-center MDT model from January 2017 to December 2024， and the ethical issues involved in the diagnosis and treatment process were analyzed. ResultsA total of 24 MDT discussion documents involving 20 children were collected， including 17 with female social gender and 3 with male social gender. The age ranged from 0.5 to 15.8 years， with children under 8 years accounting for 75%. The ethical issues primarily involved how to ensure adequate informed consent， whether surgery was necessary and its timing， and whether gender selection is reasonable and its timing. Among the 10 children raised as females who completed the gender role psychological scale assessment， 5 demonstrated masculine tendencies， all of whom had pathogenic genetic variants. Furthermore， only 1 patient changed the social gender to male. ConclusionThe diagnosis and treatment of 46, XY DSD is relatively complex， requiring multidisciplinary collaboration. This process involves numerous ethical issues and necessitates adhering to medical ethical principles. Ensuring adequate informed consent is crucial， especially for younger children. The surgery and its timing selection must adhere to the principles of beneficence， non-maleficence， and leaving room for the future. Gender selection constitutes a focus and challenge in diagnosis and treatment. Psychological scales and genetic etiologies are conducive to judgments regarding gender selection， yet multiple factors in the real world may interfere with the gender selection.

Objective:To compare the accuracy and applicability of three adult height prediction methods based on artificial intelligence-assisted bone age assessment—the Bayley-Pinneau method(BP method), the Tanner-Whitehouse 3 method(TW3 method), and China 05 method—in girls.Methods:This bidirectional cohort study collected clinical data and 690 posteroanterior X-ray images of the left hand from 278 female children who underwent pubertal development assessments at Shenzhen Children′s Hospital between January 2014 and December 2020, with follow-up until adult height was reached. Adult height prediction was performed using BP, TW3, and China 05 methods on artificial intelligence-assisted bone age assessment.Results:The BP and TW3 methods overestimated adult height by(1.7±3.7) cm and(2.6±3.0) cm, respectively, while the China 05 method underestimated adult height by(2.3±3.5) cm. The proportion of PAH within±5 cm of FAH were 80.0% for the TW3 method, 77.0% for the BP method, and 74.2% for the China 05 method, with significant differences among them( P=0.038). Analysis of cases with prediction deviations>10 cm and subgroup comparisons revealed that the TW3 and BP methods were more likely to overestimate adult height in girls aged 6.0-<8.0 years, with delayed bone age, or in the prepubertal stage(all P<0.001). The China 05 method was more prone to underestimate adult height in those with advanced bone age( P<0.001). All three methods showed significantly greater prediction errors(absolute difference between PAH and FAH) in girls with early puberty compared to those with normal pubertal development(all P<0.05). Conclusions:The TW3 and BP methods tend to overestimate adult height in girls, while the China 05 method tends to underestimate it. Caution is warranted when predicting adult height, particularly in girls under 8 years of bone age, with delayed or advanced bone age, and those with early puberty.

We report the clinical course from birth to adolescence of a patient carrying a compound heterozygous variation in the ectonucleotide pyrophosphatase/phosphodiesterase family member 1(ENPP1) gene. The patient was diagnosed with generalized arterial calcification of infancy shortly after birth, and subsequently with autosomal recessive hypophosphatemic rickets type 2 at the age of 11 years. Following effective blood pressure control, treatment with neutral phosphate, calcitriol, and vitamin D was initiated. During follow-up, no progression of vascular calcification was observed. Through this case report and a review of relevant literature, we aim to enhance clinicians′ understanding of this rare condition.

Objective:To analyze the characteristics of obstructive sleep apnea（OSA）in children with Prader-Willi syndrome (PWS),and to improve the understanding of OSA during rapid eye movement sleep.Methods:The clinical data of 13 children with PWS aged 2-14 years admitted to Shenzhen Children's Hospital from June 2017 to June 2024 were retrospectively collected as the PWS group,and 12 children with snoring caused by adenoids,tonsil hypertrophy and/or obesity were selected as the control group.The gender,age,body mass index (BMI),obstructive apnea index (OAI),oxygen desaturation index (ODI),obstructive sleep apnea hypopnea index (OAHI),rapid eye movement period OAHI(OAHIrem),non-rapid eye movement period OAHI(OAHInrem) and OAHIrem/total sleep period OAHI ratio were compared between the two groups.Multivariate linear regression was used to assess the association between PWS and OAHIrem.Results:Among the 13 children in PWS group,there were 7 males and 6 females,with an average age of (7.63±4.05) years and an average BMI of (23.06±6.12) kg/m2.Among the 12 children in control group,there were 10 males and 2 females,with an average age of (7.28±3.92) years and an average BMI of (22.41±5.68) kg/m2.There were no statistically significant differences in age,gender,and BMI between the two groups ( P>0.05).All 13 children (100%) with PWS had OSA,with 8 cases (61.53%) of mild OSA and 5 cases (38.46%) of moderate to severe OSA.OAI and ODI in PWS group were significantly higher than those in control group ( P<0.05).OAHI and OAHInrem in PWS group were higher than those in control group,but the difference was not statistically significant ( P>0.05).OAHIrem and OAHIrem/ total sleep OAHI ratio were significantly higher than those in the control group,with statistical significance ( P<0.05).Multivariate linear regression analysis showed that PWS was significantly correlated with OAHIrem/ total sleep OAH ratio (square root) ( P=0.008). Conclusion:Children with PWS have a high incidence of OSA,with a high proportion of moderate to severe OSA.They are prone to OSA with hypoxemia during rapid eye movement sleep.It is recommended that respiratory monitoring of children with PWS during rapid eye movement sleep should be strengthened,and individualized treatment plan should be formulated according to the type and severity of OSA.

Objective:To analyze the characteristics of obstructive sleep apnea（OSA）in children with Prader-Willi syndrome (PWS),and to improve the understanding of OSA during rapid eye movement sleep.Methods:The clinical data of 13 children with PWS aged 2-14 years admitted to Shenzhen Children's Hospital from June 2017 to June 2024 were retrospectively collected as the PWS group,and 12 children with snoring caused by adenoids,tonsil hypertrophy and/or obesity were selected as the control group.The gender,age,body mass index (BMI),obstructive apnea index (OAI),oxygen desaturation index (ODI),obstructive sleep apnea hypopnea index (OAHI),rapid eye movement period OAHI(OAHIrem),non-rapid eye movement period OAHI(OAHInrem) and OAHIrem/total sleep period OAHI ratio were compared between the two groups.Multivariate linear regression was used to assess the association between PWS and OAHIrem.Results:Among the 13 children in PWS group,there were 7 males and 6 females,with an average age of (7.63±4.05) years and an average BMI of (23.06±6.12) kg/m2.Among the 12 children in control group,there were 10 males and 2 females,with an average age of (7.28±3.92) years and an average BMI of (22.41±5.68) kg/m2.There were no statistically significant differences in age,gender,and BMI between the two groups ( P>0.05).All 13 children (100%) with PWS had OSA,with 8 cases (61.53%) of mild OSA and 5 cases (38.46%) of moderate to severe OSA.OAI and ODI in PWS group were significantly higher than those in control group ( P<0.05).OAHI and OAHInrem in PWS group were higher than those in control group,but the difference was not statistically significant ( P>0.05).OAHIrem and OAHIrem/ total sleep OAHI ratio were significantly higher than those in the control group,with statistical significance ( P<0.05).Multivariate linear regression analysis showed that PWS was significantly correlated with OAHIrem/ total sleep OAH ratio (square root) ( P=0.008). Conclusion:Children with PWS have a high incidence of OSA,with a high proportion of moderate to severe OSA.They are prone to OSA with hypoxemia during rapid eye movement sleep.It is recommended that respiratory monitoring of children with PWS during rapid eye movement sleep should be strengthened,and individualized treatment plan should be formulated according to the type and severity of OSA.

Objective:To compare the accuracy and applicability of three adult height prediction methods based on artificial intelligence-assisted bone age assessment—the Bayley-Pinneau method(BP method), the Tanner-Whitehouse 3 method(TW3 method), and China 05 method—in girls.Methods:This bidirectional cohort study collected clinical data and 690 posteroanterior X-ray images of the left hand from 278 female children who underwent pubertal development assessments at Shenzhen Children′s Hospital between January 2014 and December 2020, with follow-up until adult height was reached. Adult height prediction was performed using BP, TW3, and China 05 methods on artificial intelligence-assisted bone age assessment.Results:The BP and TW3 methods overestimated adult height by(1.7±3.7) cm and(2.6±3.0) cm, respectively, while the China 05 method underestimated adult height by(2.3±3.5) cm. The proportion of PAH within±5 cm of FAH were 80.0% for the TW3 method, 77.0% for the BP method, and 74.2% for the China 05 method, with significant differences among them( P=0.038). Analysis of cases with prediction deviations>10 cm and subgroup comparisons revealed that the TW3 and BP methods were more likely to overestimate adult height in girls aged 6.0-<8.0 years, with delayed bone age, or in the prepubertal stage(all P<0.001). The China 05 method was more prone to underestimate adult height in those with advanced bone age( P<0.001). All three methods showed significantly greater prediction errors(absolute difference between PAH and FAH) in girls with early puberty compared to those with normal pubertal development(all P<0.05). Conclusions:The TW3 and BP methods tend to overestimate adult height in girls, while the China 05 method tends to underestimate it. Caution is warranted when predicting adult height, particularly in girls under 8 years of bone age, with delayed or advanced bone age, and those with early puberty.

We report the clinical course from birth to adolescence of a patient carrying a compound heterozygous variation in the ectonucleotide pyrophosphatase/phosphodiesterase family member 1(ENPP1) gene. The patient was diagnosed with generalized arterial calcification of infancy shortly after birth, and subsequently with autosomal recessive hypophosphatemic rickets type 2 at the age of 11 years. Following effective blood pressure control, treatment with neutral phosphate, calcitriol, and vitamin D was initiated. During follow-up, no progression of vascular calcification was observed. Through this case report and a review of relevant literature, we aim to enhance clinicians′ understanding of this rare condition.

OBJECTIVE: To summarize the clinical features and biological characteristics of Helsmoortel Van der Aa syndrome (HVDAS) due to hotspot mutations of the ADNP gene in order to facilitate early diagnosis. METHODS: Clinical data and result of genetic testing for a girl with HVDAS due to hotspot mutation of the ADNP gene was summarized. Related literature was also reviewed. RESULTS: The patient, a 2-year-old girl, had presented with growth retardation, facial dysmorphism, psychomotor and language delay and recurrent respiratory infections. Whole exome sequencing revealed that she has harbored a heterozygous c.2496_2499delTAAA (p.Asn832Lysfs*81) variant of the ADNP gene, which was not found in either of her parents. CONCLUSION Although the typical features of the HVDAS have included intellectual disability and autism spectrum disorders, growth retardation and premature primary tooth eruption may also be present. In addition, the phenotypic difference among individuals carrying hot spot variants of the ADNP gene was not prominent.
Humans ; Female ; Child, Preschool ; Intellectual Disability/genetics* ; Homeodomain Proteins/genetics* ; Nerve Tissue Proteins/genetics* ; Abnormalities, Multiple/genetics* ; Mutation ; Rare Diseases ; Growth Disorders/genetics*

OBJECTIVE: To explore the clinical phenotype and genetic basis for a Chinese pedigree affected with familial progressive hyperpigmentation and hypopigmentation (FPHH). METHODS: Clinical data and family history for a child with FPHH were collected. Peripheral blood samples were collected from the child, his parents and two sisters. Following the extraction of DNA, high-throughput sequencing was carried out to screen for genetic variant associated with the disease. Candidate variant was verified by Sanger sequencing of his family members. RESULTS: The main clinical features of the proband have included progressive hyperpigmentation and hypopigmentation. High-throughput sequencing revealed that he has harbored a heterozygous c.105T>A (p.Asn35Lys) variant of the KITLG gene, which was unreported previously. Sanger sequencing confirmed that the variant has co-segregated with the disease phenotype in his pedigree. CONCLUSION For infants with progressive skin pigmentation and hypopigmentation spots, FPHH should be suspected. The heterozygous c.105T>A (p.Asn35Lys) variant of the KITLG gene probably underlay the FPHH in this pedigree.
Male ; Humans ; Pedigree ; Hypopigmentation/genetics* ; Phenotype ; Hyperpigmentation/genetics* ; China

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.