ObjectiveTo investigate intracranial lesion prevalence in children with central precocious puberty (CPP) and early and fast puberty (EFP), and assess impacts on progression and GnRHa response.MethodsThis retrospective study included 1,087 CPP/EFP patients (2011–2023) who underwent brain MRI. Patients were stratified by MRI findings: no lesion, other (incidental) lesions, and pathogenic lesions (hypothalamic hamartoma/glioma). Clinical, hormonal, bone age, and growth parameters were compared. GnRHa dosing and therapeutic responses were evaluated.ResultsIntracranial lesions were detected in 14.5% of girls and 19.6% of boys (P = 0.089). Detection was age-dependent: children under specific thresholds (girls <6y, boys <7y) had significantly higher rates than older peers (33.7% vs. 12.1%, P <0.001; 53.8% vs. 16.9%, P = 0.004). Pathogenic lesions (n=26) occurred exclusively in CPP, linked to earlier puberty onset (girls: 1.9y; boys: 1.0y) and elevated luteinizing hormone (LH) levels (P<0.05). Among treated girls (n=312), those with pathogenic lesions required higher 6-month GnRHa doses (P = 0.025) and exhibited faster initial growth velocity (P = 0.007), despite similar hormone suppression and 1-year height SDS changes. Incidental lesions (e.g., Rathke’s cysts) did not alter progression or treatment response.ConclusionRoutine MRI is warranted for younger CPP children (girls <6y, boys <7y) due to high pathogenic lesion rates. Conversely, older CPP and all EFP cases show low pathogenic prevalence, questioning universal MRI screening. While incidental lesions require no management alteration, CPP with hypothalamic hamartoma/glioma presents with earlier onset and heightened axis activation, necessitating higher GnRHa doses.

Objective:To describe a rare pediatric case of familial human chorionic gonadotropin (hCG) syndrome presenting with concurrent elevation of beta-hCG (β-hCG) in both blood and cerebrospinal fluid (CSF). This report aims to expand the phenotypic spectrum of this condition and discuss diagnostic challenges to avoid misdiagnosing this benign disorder as an intracranial malignancy. Methods:Clinical data were collected from the proband, an 8-year-9-month-old girl presenting with central precocious puberty (CPP) and unexplained hCG elevation. To evaluate the differential recognition of hCG variants by diverse detection antibodies, serum and CSF β-hCG levels were cross-monitored using both Abbott Architect and Roche Elecsys platforms. Additional evaluations included magnetic resonance imaging (MRI), computed tomography (CT), and pathological examination. Whole-exome sequencing (WES) and family screening of first-degree relatives were conducted to identify the etiology. A literature review regarding familial hCG syndrome was also conducted. Results:The patient was initially diagnosed with CPP due to breast development and accelerated growth. During routine screening to exclude tumor-associated precocious puberty, she was found to have elevated serum β-hCG (132.1-136.3 IU/L, Roche Elecsys) and was referred to our hospital. Imaging revealed a pineal cyst without evidence of tumor. Both serum and CSF β-hCG levels were elevated (45.58 and 103.22 IU/L, respectively; Abbott Architect), with CSF levels exceeding serum. Despite chemotherapy, radiotherapy, and pineal cyst resection (histology: central neurocytoma), hCG remained persistently elevated. Given the benign clinical course and lack of therapeutic response, segregation analysis was subsequently performed. Elevated serum β-hCG levels were identified in the patient's asymptomatic mother and prepubertal younger brother (43.79 and 64.58 mIU/mL, respectively; Abbott). Whole-exome sequencing was negative. Familial hCG syndrome was finally diagnosed, and it was determined that her CPP was an independent, concurrent condition. Oncological treatments were ceased, and the girl continued gonadotropin-releasing hormone agonist (GnRHa) treatment. Conclusion:This case report describes a novel clinical finding in familial hCG syndrome characterized by concurrent elevation of β-hCG in both serum and CSF. This finding significantly expands the phenotypic spectrum of this benign condition.

BackgroundAcromelic dysplasias, including acromicric dysplasia (AD) and geleophysic dysplasia type 2 (GD2), are ultrarare disorders caused by FBN1 variants in the transforming growth factor-β-binding protein-like domain 5 (TB5). These conditions are characterized by severe short stature and variable multisystem involvement, but genotype–phenotype correlations and treatment responses remain incompletely defined.ObjectiveTo characterize the clinical spectrum, genotype–phenotype correlations, and growth outcomes in a Chinese cohort of patients with FBN1-related AD/GD2.MethodsWe conducted a retrospective analysis of 14 patients with AD or GD2 from eight unrelated families. Clinical, radiographic, and genetic data were collected. Genotype–phenotype correlations were further explored by integrating data from two previously published cohorts (n = 52). Growth outcomes were evaluated in patients receiving recombinant human growth hormone (rhGH) therapy.ResultsAll patients exhibited severe short stature (mean height-SDS of -5.28 ± 1.13) with brachydactyly and delayed bone age. Multisystem involvement, including skeletal abnormalities, airway and otologic complications, skin thickening, joint limitation, hepatomegaly, and cardiopulmonary disease (50.0%, exclusively on GD2), was common. All the variants were heterozygous missense mutations clustered in the TB5 domain, including two novel de novo variants. Genotype–phenotype preliminary analysis revealed a greater mortality in patients with GD2 than in patients with AD (29.6%(15.9 -48.5%) vs. 4.0%(0.7-19.5%), P = 0.038). Variants with cysteine or aromatic residues substitutions were associated with increased mortality compared with that associated with other substitutions (overall P < 0.001). Eleven patients received growth-promoting therapy. Among the eight patients treated at our center, growth-promoting therapy maintained a growth velocity during the first two years (approximately 6 cm/year) but declined thereafter, with no significant improvement in height-SDS over a mean treatment duration of 3.6 years.ConclusionFBN1-related AD/GD2 represent multisystem disorders rather than isolated skeletal dysplasias. Variants affecting cysteine or aromatic residues in the TB5 domain maybe associated with worse outcomes. Growth-promoting therapy may contribute to maintaince of growth velocity but catch-up growth was not clearly observed. These findings suggest that molecular stratification may be helpful for risk assessment and clinical decision-making, pending further validation.

Background:The clearance of brain metabolic waste occurs mainly through the glymphatic system. This study aimed to explore the change of glymphatic function in children with growth hormone deficiency (GHD) using non-invasive imaging methods. Methods:This prospective research recruited 40 cases of pediatric GHD and 40 age- and gender-matched typically developing (TD) children. Glymphatic circulation, which includes the production of cerebrospinal fluid (CSF), represented by choroid plexus volume (CPV), influx, evaluated by perivascular space (PVS) burden, and waste clearance, as indirectly assessed by diffusion tensor imaging-based analysis along the perivascular space (DTI-ALPS), was explored for all participants. Partial correlations were conducted between significant magnetic resonance imaging (MRI) metrics and clinical variables in GHD children. Results:Considering the production of CSF, decreased CPV was presented in pediatric GHD [0.77±0.15 vs. 0.83±0.19 mL; Pfalse discovery rate (FDR)=0.002]. Considering influx, pediatric GHD exhibited lower PVS burden than did TD children (4.51±1.74 vs. 6.30±3.34 mL; PFDR=0.01). Considering waste clearance, DTI-ALPS decreased significantly in GHD groups (1.35±0.14 vs. 1.49±0.1; PFDR<0.001). Moreover, in children with GHD, Social Competence scores were positively correlated with PVS volume (r=0.358, P=0.032), PVS/white matter volume (WMV; r=0.420, P=0.010), and PVS/intracranial volume (ICV; r=0.410, P=0.010), whereas Activity Level was negatively correlated with CPV (r=-0.377, P=0.023). Conclusions:Our findings suggest that glymphatic dysfunction may be a pathological mechanism in pediatric GHD. Furthermore, our study demonstrates that CPV, PVS volume, and DTI-ALPS index could serve as multiple auxiliary biomarkers for assessing the glymphatic function in pediatric GHD.

BACKGROUND:Akkermansia muciniphila (A. muciniphila) has been shown to have positive effects on various metabolic diseases and partially prevent the onset of spontaneous type 1 diabetes mellitus (T1DM) in nonobese diabetic mice; however, its therapeutic efficacy in T1DM mice that have already developed T1DM remains unclear. AIM:To assess the effects of A. muciniphila intervention on the intestinal barrier, immune parameters [regulatory T (Tregs) cells/T helper 1 cells balance, signal transducer and activator of transcription 1 (STAT1)/nuclear factor kappa-B (NF-κB) signal] and intestinal flora in a streptozotocin (STZ)-induced mouse model of T1DM. METHODS:Thirty male C57BL/6 mice were randomized into three groups (n = 10 for each): Normal control (NC group), STZ-induced T1DM (STZ group), and A. muciniphila-treated T1DM (A. muciniphila group). T1DM was induced with STZ (50 mg/kg/day intraperitoneally, 5 days). Body weight, blood glucose, and water intake were monitored weekly. T1DM was modelled in all STZ- and A. muciniphila-treated mice (random blood glucose > 16.7 mmol/L). A. muciniphila group mice received oral A. muciniphila (5 × 107 colony-forming units/mouse) for 3 days. Following sacrifice, pancreatic histopathology, cytokines in splenic tissue, colonic zonula occludens-1 (ZO-1)/zonulin expression, cluster of differentiation (CD) 4+/CD8+ T-cell ratios, forkhead box P3 (FoxP3+) Tregs, STAT1/NF-κB p65 signaling, and gut microbiota composition were analyzed. RESULTS:Compared with STZ group alone, A. muciniphila group did not affect metabolic parameters. Histopathologically, STZ group and A. muciniphila group pancreatic islet cells underwent vacuolar degeneration and necrosis, exhibiting reduced counts and significantly decreased insulin positivity (P < 0.05 vs NC), with no intergroup differences. Flow cytometry and enzyme-linked immunosorbent assay revealed elevated tumor necrosis factor-alpha (TNF-α), transforming growth factor-beta (TGF-β), and zonulin levels and decreased ZO-1 expression in STZ vs NC mice (P < 0.05). Compared with STZ alone, A. muciniphila group reduced TNF-α, TGF-β, and zonulin levels while increasing the CD4+/CD8+ ratio, FoxP3+ Tregs, interleukin-4, and ZO-1 (P < 0.05). Colonic NF-κB p65 expression was higher in STZ vs NC mice (P < 0.05), with no significant A. muciniphila group/NC difference after the intervention of A. muciniphila. The expression of NF-κB p65 in A. muciniphila group was lower than that in STZ group. STAT1 expression was lower in A. muciniphila vs STZ mice (P < 0.05). 16S sequencing revealed reduced Actinobacteria abundance in A. muciniphila vs STZ mice (P < 0.05). CONCLUSION:Short-term intervention with A. muciniphila has shown positive effects on immune response parameters, exemplified by Treg-mediated restoration of immune tolerance, which may be associated with intestinal barrier enhancement and the decreased abundance of intestinal Actinobacteria.

Background:Hemophilia A is a rare, severe X-linked recessive inherited hemorrhagic disorder caused by F8 gene dysfunction, which is characterized by spontaneous or post-traumatic bleeding tendencies. The pathogenic variants identified in the F8 gene contribute to prenatal diagnosis and genetic counseling services for patients and their families. Methods:We used inverse shifting-PCR (IS-PCR), direct DNA sequencing, bioinformatics predictions, cDNA sequencing, and minigene splicing assays to explore candidate variants in a Chinese family with hemophilia A. The identified variant was classified in accordance with ACMG/AMP guidelines. Results:A novel c.6115+5_6115+6delinsAG variant at 5' splice sites (5'ss) in exon 19 was identified in a 14-year-old Chinese boy with hemophilia A by DNA sequencing, which is inherited from his asymptomatic carrier mother. Multiple bioinformatics prediction tools, including SD-Score, information content (Ri), varSEAK, and RDDC RNA splicer, predicted that this variant might affect the normal pre-mRNA splicing. Both cDNA sequencing and minigene splicing assays proved that the variant led to exon 19 skipping in the F8 gene, which was ultimately classified as pathogenic according to the ACMG/AMP guidelines. Conclusion:The c.6115+5_6115+6delinsAG variant in the F8 gene is considered to be responsible for hemophilia A in this family. This dinucleotide variant located at 5'ss of the gene is initially reported. Our study has expanded the mutation spectrum of F8 and provided a basis for prenatal and clinical diagnosis.

Background:Growth hormone deficiency (GHD) in children results from impairment of the growth hormone/insulin-like growth factor-1 (GH/IGF-1) axis. Although GHD's effects on brain structure and function have been studied, its impact on large-scale white matter (WM) structural connectivity remains poorly understood. We aimed to investigate the topological organization of WM structural connectome in pediatric GHD using diffusion tensor imaging (DTI) and graph theoretical analysis. Methods:This cross-sectional study included 58 drug-naïve children with GHD and 30 typically developing (TD) controls matched for age and gender. DTI data were analyzed using deterministic tractography, and the structural connectivity between 90 cortical and subcortical regions was assessed. Graph theoretical analysis was applied to evaluate topological parameters of the resulting graphs. Between-group comparison of networks metrics was assessed. Finally, a partial correlation analysis was performed to explore the relationship between significant topologic metrics and clinical symptom severity. Results:Compared to TD groups, the GHD patients showed altered global properties, including increased characteristic path length (P<0.001), and decreased global (P<0.001) and local efficiency (P<0.001). Regarding nodal parameters, GHD showed abnormal nodal parameters (nodal degree, efficiency, betweenness) primarily in regions associated with the default mode network (DMN), central executive network (CEN), visual network (VN), salience network (SN), sensorimotor network (SMN), basal ganglia, and left thalamus. Besides, the scores of Achenbach's Child Behavior Check List (CBCL) of GHD was positively correlated with the nodal efficiency in the left middle occipital gyrus (P=0.048, uncorrected), right inferior parietal lobe (P=0.035, uncorrected), and left middle temporal gyrus (r=0.295; P=0.034, uncorrected). Conclusions:Our findings reveal disrupted WM topological organization in children with GHD, which may potentially relate to abnormal GH/IGF-1 levels and associated with behavioral problems. These alterations in structural brain networks may underlie the behavioral challenges observed in GHD, providing new insights into the neurobiological basis of this condition.

This systematic review aims to summarize the therapeutic benefits and safety profile of long-acting PEGylated recombinant human growth hormone (PEG‑rhGH) compared with daily recombinant human growth hormone (DGH) in pediatric growth hormone deficiency (PGHD) participants. We conducted an extensive literature review utilizing multiple databases, and evaluated change in height standard deviation score (∆Ht-SDS) as the primary outcome. Secondary outcomes included change in height velocity (∆HV) and incidence of total adverse events (AEs). The meta-analysis focused on comparing the standard dose of PEG‑rhGH (0.20 mg/kg/w) and DGH. The systematic review encompassed ten studies involving a total of 1,393 participants. In RCTs and cohort studies, ∆Ht-SDS at 6 months showed no significant difference between PEG-rhGH and DGH (RCTs: MD = 0.02, 95%CI: -0.02 to 0.07, p = 0.32; Cohort studies: MD = -0.02, 95%CI: -0.24 to 0.19, p = 0.82). However, PEG-rhGH had superior ∆Ht-SDS (MD = 0.19, 95%CI: 0.03 to 0.35, p = 0.02) at 12 months. Results from RCTs also showed that the incidence of total AEs was comparable for PEG-rhGH and DGH (OR = 1.12, 95%CI: 0.84 to 1.49, p = 0.45). PEG-rhGH showed superior efficacy to DGH at 12 months and comparable efficacy at other time points. The safety profiles were similar for the two treatments.

BACKGROUND Alpha-fetoprotein (AFP) is a glycoprotein with a high serum level during pregnancy, hepatocyte proliferation, and malignant conditions in clinical settings. Hereditary persistence of alpha-fetoprotein (HPAFP) is a rare benign disorder characterized by elevated serum levels of AFP without any relevant clinical disability. Recent research has demonstrated it to be an autosomal dominant inheritance type; however, only 9 of the 30 recently reported cases could be explained by genetic analysis. CASE REPORT We describe a girl with growth retardation for 5 years who was accidentally found to have had high serum AFP for 2 years. The elevated serum AFP level delayed the application of recombinant human growth hormone (rhGH) for short stature. Multiple computed tomography (CT) scans did not reveal any space-occupying lesion in the epigastric region. Brain and spinal magnetic resonance imaging and positron emission tomography-CT showed normal results. AFP and ß-HCG levels in her cerebrospinal fluid were also normal. Finally, we found that her father and paternal grandfather also had high AFP levels, and HPAFP was diagnosed. However genetic analysis failed to identify any positive mutation related to the condition in this family. To treat the short stature, rhGH at a dose of 0.39 mg/kg of body weight was given and the patient was followed up for 20 months. Her AFP level remained stable during treatment and her height-for-age Z-score improved from -4.4 SD to -2.8 SD (mid-parental height Z-score). CONCLUSIONS We report a new family of HPAFP and emphasize that a pedigree tree could be important evidence for diagnosis, despite negative genetic test results. For our short-stature patient with HPAFP, rhGH treatment was safe and efficient.

Objectives Familial Male-Limited Precocious Puberty (FMPP) is a rare autosomal-dominant genetic condition with sexual dimorphism. We aim to summarize the clinical characteristics of FMPP patients and emphasize the use of a therapeutic regimen involving letrozole, spironolactone, and GnRHa, to augment clinician’s understanding of the disease, thus enhancing patient care. Methods We retrospectively analyzed the clinical data of 10 FMPP patients and conducted follow-up assessments of adult height in six patients. Results Out of the 10 FMPP cases, five had the LHCGR M398T mutation, three exhibited the LHCGR A564G mutation, and two had the LHCGR T577I mutation. All patients initially presented with symptoms like penile enlargement, frequent erections, and rapid growth. Their median age at diagnosis was 4.67 years with bone age being 9 years. Four patients were untreated with a median adult height of 162 cm. Six patients underwent treatment between ages 3.58 and 5.5 years noting decreased frequency of erections, slower growth rate, and delayed bone age progression. Secondary Central Precocious Puberty (CPP) developed between ages 5 and 6.5 years in all cases, necessitating additional GnRHa treatment. Two treated cases reached an adult height of 176 cm and 173 cm, respectively, without any significant adverse effects. Conclusions The most prevalent genotype among FMPP patients in this study was the LHCGR M398T mutation. Early intervention using a regimen including letrozole and spironolactone, and later GnRHa, appears beneficial in limiting physical signs and improving adult height without major side effects. However, the longer-term effects on fertility require further investigation.

Background: Pediatric growth hormone deficiency (GHD) is a disease resulting from the impaired growth hormone-insulin-like growth factor-1 (GH-IGF-1) axis, but the effects of GHD on children's behavior and brain microstructural structure alterations have not yet been fully clarified. We aimed to investigate the quantitative profiles of gray matter and white matter in pediatric GHD using synthetic magnetic resonance imaging (MRI). Methods: The data of 50 children with GHD and 50 typically developing (TD) children were prospectively collected. Group differences in brain volumetric parameters, individual-level T1 and T2 relaxometry values, and myelin volume fraction (MVF) were assessed. Subsequently, magnetic resonance-based indices with significant differences between groups were correlated with clinical variables via partial correlation. Results: Compared with TD children, children with GHD showed significantly decreased whole-brain gray-matter volume [P false discovery rate (PFDR) <0.001] and increased non-gray-matter/white-matter/ cerebrospinal fluid (NoN) volume (PFDR<0.001). For gray-matter microstructural profiles, altered T1 and T2 relaxometry values in children with GHD were mainly distributed in the default mode (PFDR<0.001) and central executive networks (PFDR<0.001). For white-matter microstructural profiles, widespread increased regional MVF was mainly distributed in the corpus callosum, corticospinal tract, internal capsule, external capsule, and cingulum (all PFDR values <0.001). Meanwhile, the T2 relaxation values in the left cuneus (r=0.400; P=0.005) and MVF in the right corticospinal tract (r=0.313; P=0.032) had a positive relationship with IGF-1. Conclusions: Altered T1 and T2 relaxometry values and MVF in gray and white matter indicate the relevance of the default mode, central executive, somatosensory, visual, and cerebellar networks underlying pediatric GHD, which may imply the involvement of the GH-IGF-1 axis and myelin in the pathophysiological mechanism of GHD. Moreover, the brain microstructure alteration in cortico-striatallimbic loop might be influenced by the GH-IGF-1 axis and play an important role in the behavioral impairments in children with GHD.

Several evidence gaps exist regarding the use of long-acting polyethylene glycol recombinant human growth hormone (PEG-rhGH) in children with idiopathic short stature (ISS), particularly studies conducted in real-world settings, with long-term follow-up, involving varied dosing regimens, and in comparison with daily rhGH. The study aimed to evaluate the effectiveness, safety, and adherence of once-weekly PEG-rhGH for catch-up growth in children with prepubertal ISS compared to daily rhGH. A real-world retrospective cohort study was conducted in prepubertal children with ISS in China. Children who voluntarily received once-weekly PEG-rhGH or daily rhGH were included and were followed up for 2 years. Ninety-five children were included, 47 received PEG-rhGH 0.2–0.3 mg/kg weekly and 48 received daily rhGH. Outcome measures included effectiveness in catch-up growth, adverse events, and treatment adherence. Height velocity increased significantly in both groups during rhGH therapy. In children who received PEG-rhGH treatment, height velocity was 10.59 ± 1.37 cm/year and 8.75 ± 0.86 cm/year in the first and second year, respectively, which were significantly more than those who received daily rhGH (9.80 ± 1.05 cm/year, P = 0.002, and 8.03 ± 0.89 cm/year, P < 0.001). The height standard deviation score improved at the end of the second year for all children (P < 0.001). However, children who received PEG-rhGH showed more excellent improvement than those with daily rhGH (1.65 ± 0.38 vs. 1.50 ± 0.36, P = 0.001). In children who received PEG-rhGH, lower missed doses were observed than those with daily rhGH (0.75 ± 1.06 vs. 4.4 ± 2.0, P < 0.001). No serious adverse events were observed. Conclusion: PEG-rhGH demonstrated superior effectiveness and adherence compared to daily rhGH in the treatment of children with ISS. The safety profiles were similar between the two treatments.

Morphology of right ventricular outflow tract (RVOT) is potentially related to cardiovascular outcomes. However, this relationship still remains to be verified with direct evidence. We retrospectively reviewed cases from the autopsy specimen library in the Center of Forensic Medicine in Sun Yat-sen University from 2017 to 2023. Six RVOT morphological characteristics were measured and their association with cardiovascular diseases (CVDs), sudden cardiac death (SCD) and age at death was evaluated. Relationship between myocardial fibrosis in RVOT and CVDs was investigated. RVOT characteristics were recruited by machine learning algorithms for diagnosing CVDs. A total of 2370 cases were finally recruited. Perimeter of sub-valve plane (pSBV) in RVOT was positively associated with risk of CVDs and SCD (OR: 1.21, 95%CI: 1.07-1.37, p = 0.003; OR: 1.33, 95%CI: 1.16-1.52, p < 0.001). Compared with thickness of septum (tS) < 3.0 mm, tS >= 3.0 mm was associated with premature death in disease-dominant death (beta=-0.16, 95%CI: -0.20 to -0.11, p < 0.001) and SCD (beta=-0.15, 95%CI: -0.21 to -0.10, p < 0.001). Degree of myocardial fibrosis in the posterior septum was increased in coronary atherosclerosis (6.86%+/- 2.48% vs. 4.91%+/- 2.14%, p = 0.011) and cardiomyopathies (8.11%+/- 3.24% vs. 4.88%+/- 3.11%, p = 0.005). A logistic regression model, recruiting age, left and right ventricular wall thickness, pSBV, circumference of pulmonary annulus and aortic annulus, was elected as an optimal diagnostic model of CVDs, yielding AUC of 0.734 (95%CI: 0.705-0.763), 0.781 (0.740-0.821) and 0.763 (0.725-0.800) in training, validation and test sets. Increased pSBV significantly correlates with higher risk of CVDs and SCD. And tS >= 3.0 mm is an independent risk factor of premature death regardless of diseases.

BACKGROUND:Accumulating evidences indicate regional grey matter (GM) morphology alterations in pediatric growth hormone deficiency (GHD); however, large-scale morphological brain networks (MBNs) undergo these patients remains unclear. OBJECTIVE:To investigate the topological organization of individual-level MBNs in pediatric GHD. METHODS:Sixty-one GHD and 42 typically developing controls (TDs) were enrolled. Inter-regional morphological similarity of GM was taken to construct individual-level MBNs. Between-group differences of topological parameters and network-based statistics analysis were compared. Finally, association relationship between network properties and clinical variables was analyzed. RESULTS:Compared to TDs, GHD indicated a disturbance in the normal small-world organization, reflected by increased Lp, γ, λ, σ and decreased Cp, Eglob (all PFDR < 0.017). Regarding nodal properties, GHD exhibited increased nodal profiles at cerebellum 4-5, central executive network-related left inferior frontal gyrus, limbic regions-related right posterior cingulate gyrus, left hippocampus, and bilateral pallidum, thalamus (all PFDR < 0.05). Meanwhile, GHD exhibited decreased nodal profiles at sensorimotor network -related bilateral paracentral lobule, default-mode network-related left superior frontal gyrus, visual network -related right lingual gyrus, auditory network-related right superior temporal gyrus and bilateral amygdala, right cerebellum 3, bilateral cerebellum 10, vermis 1-2, 3, 4-5, 6 (all PFDR < 0.05). Furthermore, serum markers and behavior scores in GHD group were correlated with altered nodal profiles (P ≤ 0.046, uncorrected). CONCLUSION:GHD undergo an extensive reorganization in large-scale individual-level MBNs, probably due to abnormal cortico-striatal-thalamo-cerebellum loops, cortico-limbic-cerebellum, dorsal visual-sensorimotor-striatal, and auditory-cerebellum circuitry. This study highlights the crucial role of abnormal morphological connectivity underlying GHD, which might result in their relatively slower development in motor, cognitive, and linguistic functional within behavior problem performance.