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Exome sequencing (ES) has identified biallelic kinesin family member 12 (KIF12) mutations as underlying neonatal cholestatic liver disease. We collected information on onset and progression of this entity. Among consecutively referred pediatric patients at our centers, diagnostic ES identified 4 patients with novel, biallelic KIF12 variants using the human GRCh38 reference sequence, as KIF12 remains incompletely annotated in the older reference sequence GRCh37. A review of these and of 21 reported patients with KIF12 variants found that presentation with elevated serum transaminase activity in the context of trivial respiratory infection, without clinical features of liver disease, was more common (n = 18) than manifest cholestatic disease progressing rapidly to liver transplantation (LT; n = 7). Onset of liver disease was at age <1 year in 15 patients; LT was more common in this group. Serum gamma‐glutamyl transpeptidase activity (GGT) was elevated in all patients, and total bilirubin was elevated in 15 patients. Liver fibrosis or cirrhosis was present in 14 of 18 patients who were biopsied. The 16 different pathogenic variants and 11 different KIF12 genotypes found were not correlated with age of onset or progression to LT. Identification of biallelic pathogenic KIF12 variants distinguishes KIF12‐related disease from other entities with elevated GGT. [ABSTRACT FROM AUTHOR]

Aim: To examine possible geographical and temporal differences in the incidence of childhood‐onset inflammatory bowel disease (IBD) in Norway, motivated by previous research indicating relevant environmental factors explaining changing epidemiology. Methods: We analysed data from children born in Norway from 2004 to 2012 (n = 541 036) in a registry‐based nationwide study. After validating registry diagnoses against medical records, we defined IBD as ≥2 entries of International Classification of Diseases, 10th revision (ICD‐10) codes K50, K51 and K52.3 in the Norwegian Patient registry. We estimated hazard ratios (HR) for IBD across four geographical regions with a south‐to‐north gradient and the incidence by period of birth. Results: By the end of follow‐up on 31 December 2020, 799 IBD diagnoses were identified (Crohn's disease: n = 465; ulcerative colitis, n = 293, IBD: unclassified, n = 41). Compared to children in the southernmost region, there was almost a two‐fold HR for IBD in children in the most Northern region (HR = 1.94, 95% Cl = 1.47–2.57; Mid region: HR = 1.68, 95% CI = 1.29–2.19, ptrend <0.001). These estimates remained largely unchanged after adjustment for potential confounding factors. The cohorts born in 2004–2006 and 2010–2012 had comparable cumulative incidences, with a slightly higher incidence for those born in 2007–2009. Conclusion: We observed an increase in the risk of IBD by increasing latitude which may suggest that environmental factors influence the development of IBD, although non‐causal explanations cannot be ruled out. [ABSTRACT FROM AUTHOR]

Objectives There is little data on renal relapse in childhood-onset LN (cLN). We investigate the incidence, predictive factors and outcomes related to renal relapse. Methods We conducted a retrospective cohort study of all cLN diagnosed at ≤18 years between 2001–2021 to investigate the incidence and outcomes related to renal relapse. Results Ninety-five Chinese cLN patients (91% proliferative LN) were included. Induction immunosuppression was prednisolone and CYC [ n  = 36 (38%)] or MMF [ n  = 33 (35%)]. Maintenance immunosuppression was prednisolone and MMF [ n  = 53 (54%)] or AZA [ n  = 29 (31%)]. The rates of complete remission/partial remission (CR/PR) at 12 months were 78.9%/7.4%. Seventy renal relapses occurred in 39 patients over a follow-up of 10.2 years (s. d. 5.9) (0.07 episode/patient-year). Relapse-free survival was 94.7, 86.0, 80.1, 71.2, 68.3, 50.3 and 44.5% at 1, 2, 3, 4, 5, 10 and 20 years, respectively. Multivariate analysis showed that LN diagnosis <13.1 years [adjusted hazard ratio (HRadj) 2.59 995% CI 1.27, 5.29), P  = 0.01], AZA maintenance [HRadj 2.20 (95% CI 1.01, 4.79), P  = 0.05], PR [HRadj 3.9 (95% CI 1.03, 9.19), P  = 0.01] and non-remission [HRadj 3.08 (95% CI 1.35, 11.3), P  = 0.04] at 12 months were predictive of renal relapse. Renal relapse was significantly associated with advanced chronic kidney disease (stages 3–5) and end-stage kidney disease (17.9% vs 1.8%, P  < 0.01). Furthermore, patients with renal relapse showed an increased incidence of infections (30.8% vs 10.7%, P  = 0.02), osteopenia (38.5% vs 17.9%, P  = 0.04) and hypertension (30.8% vs 7.1%, P  < 0.01). Conclusion Renal relapse is common among cLN, especially among young patients, and is associated with an increased incidence of morbidity and mortality. Attaining CR and the use of MMF appear to decrease the incidence of renal relapse. [ABSTRACT FROM AUTHOR]

Takayasu arteritis (TAK) is a less common large-vessel vasculitis which can occur in either children or adults. However, differences between pediatric-onset and adult-onset TAK have not been systematically analyzed. We undertook a systematic review (pre-registered on PROSPERO, identifier CRD42022300238) to analyze differences in clinical presentation, angiographic involvement, treatments, and outcomes between pediatric-onset and adult-onset TAK. We searched PubMed (MEDLINE and PubMed Central), Scopus, major recent international rheumatology conference abstracts, Cochrane database, and clinicaltrials.gov, and identified seven studies of moderate to high quality comparing pediatric-onset and adult-onset TAK. Meta-analysis of 263 pediatric-onset and 981 adult-onset TAK suggested that constitutional features (fever, and in subgroup analyses, weight loss), hypertension, headache, and sinister features of cardiomyopathy, elevated serum creatinine, and abdominal pain were more frequent in pediatric-onset TAK, whereas pulse loss/pulse deficit and claudication (particularly upper limb claudication) were more frequent in adult-onset TAK. Hata's type IV TAK was more common in pediatric-onset TAK, and Hata's type I TAK in adult-onset TAK. Children with TAK also appeared to require more intense immunosuppression with more frequent use of cyclophosphamide, biologic DMARDs, tumor necrosis factor alpha inhibitors, and, in subgroup analyses, tocilizumab in pediatric-onset TAK than in adult-onset TAK. Surgical or endovascular procedures, remission, and risk of mortality were similar in both children and adults with TAK. No studies had compared patient-reported outcome measures between pediatric-onset and adult-onset TAK. Distinct clinical features and angiographic extent prevail between pediatric-onset and adult-onset TAK. Clinical outcomes in these subgroups require further study in multicentric cohorts. Key Points • Pediatric-onset TAK more commonly presents with constitutional features, hypertension, cardiomyopathy, elevated serum creatinine, and abdominal pain. • Adult-onset TAK more commonly presents with pulse loss/pulse deficit or claudication (particularly of the upper limbs). • Angiographic type IV is more common in children, and type I in adults. • Remission and mortality are similar in pediatric-onset and adult-onset TAK. [ABSTRACT FROM AUTHOR]

Background: There is a lack of information on changes in hospital admission rates for childhood-onset schizophrenia (COS), or on patient characteristics, to inform clinical research and health service provision. Aims: To report age- and sex-specific incidence rates of hospital admissions and day patient care for schizophrenia (ICD-10 F20) and non-affective psychosis (ICD-10 F20-29), by year of occurrence and age, in childhood and adolescence. Methods: Population-based study using person-linked data for England (available 2001–2016); time-periods in single years and 4-year groups. Results: Hospitalised incidence for schizophrenia increased with increasing age, from 0.03 (95% confidence interval (CI) 0.02–0.05) and 0.01 (0–0.01) per 100,000 in, respectively, males and females aged 5–12 years, to 3.67 (3.44–3.91) in males and 1.58 (1.43–1.75) in females aged 13–17 years. There was no gender difference in hospitalised incidence rates in children aged 5–12, but in 13–17 years old, there was a male excess. Rates for schizophrenia were stable over time in 5–12 years old. In ages 13–17, rates for schizophrenia decreased between 2001–2004 and 2013–2016 in males, from 6.65 (6.04–7.31) down to 1.40 (1.13–1.73), and in females from 2.42 (2.05–2.83) to 1.18 (0.92–1.48). The hospitalisation rates for schizophrenia and non-affective psychosis, combined, in 13–17 years old decreased in males from 14.20 (13.30–15.14) in 2001–2004 to 10.77 (9.97–11.60) in 2013–2016, but increased in females from 7.49 (6.83–8.20) to 10.16 (9.38–11.00). Conclusions: The study confirms that childhood-onset schizophrenia is extremely rare, with only 32 cases identified over a 15-year period in the whole of England. The incidence of schizophrenia and non-affective psychosis increased substantially in adolescence; however, the marked reduction in the proportion of those diagnosed with schizophrenia in this age group suggests a possible change in diagnostic practice. [ABSTRACT FROM AUTHOR]

Background: This work aims to describe the clinico-radiological phenotype of UBTF c.628G>A (p.Glu210Lys) pathogenic variant-related neurodegeneration in childhood. Methods: We describe the progress of clinical and neuroimaging features in a male individual who had childhood-onset neuroregression and carried the heterozygous UBTF c.628G>A (p.Glu210Lys) pathogenic variant. Clinical cases reported in the literature are reviewed. Results: Fifteen individuals, from 14 reported cases and the index case, were noted. The median age at onset of neurodegeneration was 3 years. Clinical phenotype was consistent among the affected individuals, with progressive motor, speech, cognitive, and social–emotional regression together with ataxia and prominent pyramidal and extrapyramidal symptoms and signs in early to middle childhood. All individuals had the same brain MRI features in terms of symmetric and diffuse T2 high signal intensity over the bilateral subcortical, periventricular, and peritrigonal white matter and progressive cortical and subcortical supratentorial atrophy. Two individuals were reported to have bilateral thalamic involvement. All individuals had profound intellectual disability with loss of verbal and/or ambulatory functions during follow-up. Conclusions: Individuals with the heterozygous UBTF c.628G>A (p.Glu210Lys) pathogenic variant had consistent clinical progress and neuroimaging features. Familiarity with this clinico-radiological phenotype may allow earlier diagnosis of this rare disease. [ABSTRACT FROM AUTHOR]

Background: There is growing evidence linking low levels of vitamin D3 to an increased risk of many autoimmune diseases. Compared to the general population, hypovitaminosis D is more prevalent among children with systemic lupus erythematosus (SLE), which can be associated with sun exposure avoidance, long-term corticosteroid treatment, and renal disease. Therefore, we launched this study to assess the correlation between 25 (OH) D3 (VitD3) levels and the disease activity of children with SLE (cSLE) in Taiwan. Methods: From September to December 2018, we recruited 31 cSLE patients from the Pediatric Out-patient Department of Taichung Veterans General Hospital. Their basic data, including SLE disease index 2000 (SLEDAI-2K) score, laboratory values, prescribed drugs and VitD3 levels were collected and analyzed statistically. Results: The mean serum VitD3 concentration was 19.7 ± 7.9 ng/mL and SLEDAI-2K 6.2 ± 5.0. Those patients (N = 16) with an SLEDAI-2K≦4 had higher VitD3 levels when compared to those (N = 15) with an SLEDAI-2K>4 (22.9 ± 7.7 vs 16.3 ± 6.7 points, p = 0.020). Five patients not taking systemic corticosteroids (SCS) had significantly higher VitD3 levels and lower SLEDAI-2K than those who took SCS (N = 26). Additionally, we found VitD3 levels to be negatively correlated to SLEDAI-2K (rs = −0.55, p = 0.001) and daily SCS dosages (rs = −0.49, p = 0.005). Conclusion: This study shows that VitD3 deficiency is common in patients with cSLE. It was also noted that serum VitD3 levels negatively correlate to SLEDAI-2K, which can be partially explained by less usage of SCS. [ABSTRACT FROM AUTHOR]

Background: There is growing evidence linking low levels of vitamin D3 to an increased risk of many autoimmune diseases. Compared to the general population, hypovitaminosis D is more prevalent among children with systemic lupus erythematosus (SLE), which can be associated with sun exposure avoidance, long-term corticosteroid treatment, and renal disease. Therefore, we launched this study to assess the correlation between 25 (OH) D3 (VitD3) levels and the disease activity of children with SLE (cSLE) in Taiwan. Methods: From September to December 2018, we recruited 31 cSLE patients from the Pediatric Out-patient Department of Taichung Veterans General Hospital. Their basic data, including SLE disease index 2000 (SLEDAI-2K) score, laboratory values, prescribed drugs and VitD3 levels were collected and analyzed statistically. Results: The mean serum VitD3 concentration was 19.7 ± 7.9 ng/mL and SLEDAI-2K 6.2 ± 5.0. Those patients (N = 16) with an SLEDAI-2K≦4 had higher VitD3 levels when compared to those (N = 15) with an SLEDAI-2K>4 (22.9 ± 7.7 vs 16.3 ± 6.7 points, p = 0.020). Five patients not taking systemic corticosteroids (SCS) had significantly higher VitD3 levels and lower SLEDAI-2K than those who took SCS (N = 26). Additionally, we found VitD3 levels to be negatively correlated to SLEDAI-2K (rs = -0.55, p = 0.001) and daily SCS dosages (rs = -0.49, p = 0.005). Conclusion: This study shows that VitD3 deficiency is common in patients with cSLE. It was also noted that serum VitD3 levels negatively correlate to SLEDAI-2K, which can be partially explained by less usage of SCS. [ABSTRACT FROM AUTHOR]

Clustered regularly interspaced short palindromic repeats and CRISPR-associated protein 9 (CRISPR-Cas9) is an ancient prokaryotic defense system that precisely cuts foreign genomic DNA under the control of a small number of guide RNAs. The CRISPR-Cas9 system facilitates efficient double-stranded DNA cleavage that has been recently adopted for genome editing to create or correct inherited genetic mutations causing disease. Congenital heart disease (CHD) is generally caused by genetic mutations such as base substitutions, deletions, and insertions, which result in diverse developmental defects and remains a leading cause of birth defects. Pediatric CHD patients exhibit a spectrum of cardiac abnormalities such as septal defects, valvular defects, and abnormal chamber development. CHD onset occurs during the prenatal period and often results in early lethality during childhood. Because CRISPR-Cas9-based genome editing technology has gained considerable attention for its potential to prevent and treat diseases, we will review the CRISPR-Cas9 system as a genome editing tool and focus on its therapeutic application for CHD.

Abstract Background Childhood-onset systemic lupus erythematosus (cSLE) is a kind of chronic inflammatory disease characterized by a highly abnormal immune system. This study aimed to detect the serum levels of Th (T helper) cytokines (IL-2, IL-4, IL-5, IL-6, IL-9, IL-10, IL-13, IL-17A, IL-17F, IL-21, IL-22, IFN-γ and TNF-α) in cSLE and healthy controls, and then to elucidate their association with clinical manifestations, disease activity and laboratory parameters. In order to provide clues for early diagnosis and timely intervention treatment of cSLE patients. Methods A total of 33 children with cSLE and 30 healthy children were enrolled in this study. Children in the cSLE group were classified into the inactive or active cSLE group according to their SLE disease activity index 2000 (SLEDAI-2 K) score. Th cytokine profiles in the peripheral blood were detected and analysed. Results Levels of IL-2, IL-10 and IL-21 in the cSLE group were significantly higher than those in the healthy control group (P

Background: This work aims to describe the clinico-radiological phenotype of UBTF c.628G>A (p.Glu210Lys) pathogenic variant-related neurodegeneration in childhood. Methods: We describe the progress of clinical and neuroimaging features in a male individual who had childhood-onset neuroregression and carried the heterozygous UBTF c.628G>A (p.Glu210Lys) pathogenic variant. Clinical cases reported in the literature are reviewed. Results: Fifteen individuals, from 14 reported cases and the index case, were noted. The median age at onset of neurodegeneration was 3 years. Clinical phenotype was consistent among the affected individuals, with progressive motor, speech, cognitive, and social–emotional regression together with ataxia and prominent pyramidal and extrapyramidal symptoms and signs in early to middle childhood. All individuals had the same brain MRI features in terms of symmetric and diffuse T2 high signal intensity over the bilateral subcortical, periventricular, and peritrigonal white matter and progressive cortical and subcortical supratentorial atrophy. Two individuals were reported to have bilateral thalamic involvement. All individuals had profound intellectual disability with loss of verbal and/or ambulatory functions during follow-up. Conclusions: Individuals with the heterozygous UBTF c.628G>A (p.Glu210Lys) pathogenic variant had consistent clinical progress and neuroimaging features. Familiarity with this clinico-radiological phenotype may allow earlier diagnosis of this rare disease.

Background: Childhood-onset systemic lupus erythematosus (cSLE) is a kind of chronic inflammatory disease characterized by a highly abnormal immune system. This study aimed to detect the serum levels of Th (T helper) cytokines (IL-2, IL-4, IL-5, IL-6, IL-9, IL-10, IL-13, IL-17A, IL-17F, IL-21, IL-22, IFN-γ and TNF-α) in cSLE and healthy controls, and then to elucidate their association with clinical manifestations, disease activity and laboratory parameters. In order to provide clues for early diagnosis and timely intervention treatment of cSLE patients.Methods: A total of 33 children with cSLE and 30 healthy children were enrolled in this study. Children in the cSLE group were classified into the inactive or active cSLE group according to their SLE disease activity index 2000 (SLEDAI-2 K) score. Th cytokine profiles in the peripheral blood were detected and analysed.Results: Levels of IL-2, IL-10 and IL-21 in the cSLE group were significantly higher than those in the healthy control group (P < 0.05, P < 0.01 and P < 0.01, respectively). Expression of IL-2, IL-10 and IL-21 in the active cSLE group was significantly higher than that in the healthy control group (P < 0.05, P < 0.01 and P < 0.05, respectively), but that of IL-22 expression was markedly lower in the active cSLE group than in the healthy control group (P < 0.001). IL-21 in the inactive SLE group was significantly higher than that in the healthy control group (P < 0.05), and levels of IL-2 and IL-10 in the active cSLE group were significantly higher than those in the inactive cSLE group (P < 0.01 and P < 0.05). In-depth analysis showed that after excluding age, gender and drug interference, the levels of IL-2 (P < 0.05), IL-6 (P < 0.05) and IL-10 (P < 0.05) were still positively correlated with SLEDAI-2 K scores. However, the levels of IL-6 (P < 0.05) and IFN- γ (P < 0.05) were still negatively correlated with CD4+/CD8+, and the concentration of IL-6 (P < 0.05) was still positively correlated with the occurrence of nephritis.Conclusion: This study provides a theoretical basis for the discovery of effective methods to regulate imbalance in T lymphocyte subsets in cSLE, which may lead to new approaches for the diagnosis of cSLE. [ABSTRACT FROM AUTHOR]

Background: Dystonia is a relatively common feature of spinocerebellar ataxia 3 (SCA3). Childhood onset of SCA3 is rare and typically associated with either relatively large, or homozygous, CAG repeat expansions. Case report: We describe a 10-year-old girl with SCA3, who presented with tongue dystonia in addition to limb dystonia and gait ataxia due to a heterozygous expansion of 84 repeats in ATXN3. Discussion: Diagnosis of the SCAs can be challenging, and even more so in children. Tongue dystonia has not previously been documented in SCA3.

Background and purpose: Childhood‐onset autosomal dominant cerebellar ataxia type 7 (SCA7) is a severe disease which leads to premature loss of ambulation and death. Early diagnosis of SCA7 is of major importance for genetic counselling and still relies on specific genetic testing, driven by clinical expertise. However, the precise phenotype and natural history of paediatric SCA7 has not yet been fully described. Our aims were to describe the natural history of SCA7 in a large multicentric series of children of all ages, and to find correlates to variables defining this natural history. Methods: We collected and analysed clinical data from 28 children with proven SCA7. All had clinical manifestations of SCA7 and either a definite number of CAG repeats in ATXN7 or a long expansion > 100 CAG. Results: We identified four clinical presentation patterns related to age at onset. Children of all age groups had cerebellar atrophy and retinal dystrophy. Our data, combined with those in the literature, suggest that definite ranges of CAG repeats determine paediatric SCA7 subtypes. The number of CAG repeats inversely correlated to all variables of the natural history. Age at gait ataxia onset correlated accurately to age at loss of walking ability and to age at death. Conclusion: SCA7 in children has four presentation patterns that are roughly correlated to the number of CAG repeats. Our depiction of the natural history of SCA7 in children may help in monitoring the effect of future therapeutic trials. [ABSTRACT FROM AUTHOR]

Sodium voltage-gated channel α subunit 5 (SCN5A)-mutations may cause an array of arrhythmogenic syndromes most frequently as an autosomal dominant trait, with incomplete penetrance, variable expressivity and male predominance. In the present study, we retrospectively describe a group of Mexican patients with SCN5A-disease causing variants in whom the onset of symptoms occurred in the pediatric age range. The study included 17 patients with clinical diagnosis of primary electrical disease, at least one SCN5A pathogenic or likely pathogenic mutation and age of onset SCN5A mutation carriers were affected (overall penetrance 53.3%), and penetrance was higher in males (63.3%, 19 affected/30 mutation carriers) than in females (33.3%, 5 affected/15 carriers). In conclusion, pediatric patients with SCNA-disease causing variants presented mainly as overlap syndrome, with predominant loss-of-function phenotypes of sick sinus syndrome (SSS), progressive cardiac conduction disease (PCCD) and ventricular arrhythmias.

Objective: Childhood-onset systemic lupus erythematosus (cSLE) is usually a more severe and aggressive disease than adult-onset SLE (aSLE), but cellular and subcellular reasons for these differences are not well understood. The present study analyzed Th subsets, STAT1/STAT5 signaling response, and cytokine profiles of cSLE.Methods: FOXP3+ regulatory (Treg) and effector Th subsets, expression and phosphorylation of STAT1/STAT5 in Th, and cytokine profiles were measured in the peripheral blood of patients with cSLE and healthy controls (HC), using flow cytometry and immunoassay on a biochip.Results: Significant correlation between expression of the activation marker HLA-DR and decreased Th counts, an increase in the percentage of FOXP3+ Th, and a decrease in the activated Treg (aTreg) subset among them were found in cSLE. In contrast to our previous findings in aSLE, no significant differences in percentages and a significant decrease in the numbers of the naive-resting Treg (rTreg) subset compared to HC were found. The percentages of CD25- cells, possibly reflecting interleukin 2 depletion, were significantly increased in cSLE aTreg, but not in the rTreg subset. Consistent with the results of our previous studies in aSLE, increased expression of STAT1, along with significant correlation between decreased Th counts and their increased basal phosphorylation of STAT5, were also found in cSLE.Conclusion: Our results suggest that the key difference in Treg homeostasis between cSLE and aSLE is in the rTreg subset. However, perturbed aTreg homeostasis, increased levels of STAT1 protein, and homeostatic STAT5 signaling appear to be intrinsic characteristics of the disease, present in cSLE and aSLE alike. [ABSTRACT FROM AUTHOR]

• North Sea progressive myoclonus epilepsy (NS-PME), a disease caused by mutations in the GOSR2 gene, is exacerbated by heat. • Consistently, a Drosophila fruitfly model for NS-PME shows heat-induced seizure-like behavior. • Membrin , the Drosophila orthologue of GOSR2, is required in glia, but not in neurons to prevent heat-induced seizures. • Sodium barbital treatment to NS-PME flies decreased heat-induced seizures. • The fly model can be used to understand the pathophysiology of NS-PME and to identify treatment strategies. Progressive myoclonic epilepsies (PMEs) comprise a group of rare disorders of different genetic aetiologies, leading to childhood-onset myoclonus, myoclonic seizures and subsequent neurological decline. One of the genetic causes for PME, a mutation in the gene coding for Golgi SNAP receptor 2 (GOSR2), gives rise to a PME-subtype prevalent in Northern Europe and hence referred to as North Sea Progressive Myoclonic Epilepsy (NS-PME). Treatment for NS-PME, as for all PME subtypes, is symptomatic; the pathophysiology of NS-PME is currently unknown, precluding targeted therapy. Here, we investigated the pathophysiology of NS-PME. By means of chart review in combination with interviews with patients (n = 14), we found heat to be an exacerbating factor for a majority of NS-PME patients (86%). To substantiate these findings, we designed a NS-PME Drosophila melanogaster model. Downregulation of the Drosophila GOSR2-orthologue Membrin leads to heat-induced seizure-like behaviour. Specific downregulation of GOSR2/Membrin in glia but not in neuronal cells resulted in a similar phenotype, which was progressive as the flies aged and was partially responsive to treatment with sodium barbital. Our data suggest a role for GOSR2 in glia in the pathophysiology of NS-PME. [ABSTRACT FROM AUTHOR]

At least 15 candidate genes have been implicated in hypoparathyroidism (HP). However, comprehensive screening of causative genes for HP is lacking. Here, we investigated the genotype spectrum in a large group of Chinese patients with childhood onset HP. A total of 173 patients with childhood onset HP were analyzed using targeted next‐generation sequencing (NGS), including 15 candidate genes combined with multiplex ligation‐dependent probe amplification (MLPA) of the TBX1 gene. Twenty‐seven pathogenic or likely pathogenic mutations in five genes (TBX1, AIRE, GATA3, FAM111A, and CASR) including 13 novel variants in 23 patients, and 12 variants of uncertain clinical significance in five genes (GATA3, CASR, FAM111A, GCM2, and PTH) in 11 patients, were identified by NGS. Additionally, an entire gene deletion of TBX1 in 25 patients was found by TBX1‐MLPA. Combined with clinical data, 26 (15.0%) cases of DiGeorge syndrome (OMIM #188400), nine (5.2%) autoimmune polyglandular syndrome type 1 (OMIM #240300), eight (4.6%) autosomal dominant hypocalcemia type 1 (OMIM #601198), four (2.3%) hypoparathyroidism‐deafness‐renal dysplasia syndrome (OMIM #146255), and one (0.6%) Kenny‐Caffey syndrome type 2 (OMIM #127000) were verified. Among them, 16 of 26 (61.5%) DiGeorge syndrome cases were undiagnosed due to the lack of obvious clinical clues before genetic testing. The onset age of patients with mutations (median [interquartile range], 2.8 [0.1, 9.6] years) was significantly earlier than those without mutations (13.0 [8.8, 15.0] years) (p < 0.001). Family history, early onset age, especially prior to 5 years old, and extraparathyroid manifestations were clues for hereditary HP. The combined targeted NGS and TBX‐1 MLPA were conveniently and effectively used for comprehensive genetic screening in this large Chinese cohort of childhood onset HP patients. Genetic defects were identified in 27.7% of early‐onset HP patients, including four kinds of syndromic HP and one isolated HP. A total of 13 novel mutations were detected, which expands the mutation spectrum of hypoparathyroidism. © 2019 American Society for Bone and Mineral Research. [ABSTRACT FROM AUTHOR]

The genetic background of Ménière's disease (MD) was studied in one patient with childhood‐onset MD and his grandfather affected with middle age–onset MD. Whole‐exome sequencing was performed and the data were compared to 76 exomes from unrelated subjects without MD. Thirteen rare inner ear expressed variants with pathogenic estimations were observed in the case of childhood‐onset MD. These variants were in genes involved in the formation of cell membranes or the cytoskeleton and in genes participating in cell death or gene‐regulation pathways. His grandfather shared two of the variants: p.Y273N in HMX2 and p.L229F in TMEM55B. HMX2 p.Y273N was considered the more likely candidate for MD, as the gene is known to affect both hearing and vestibular function. The variant in the HMX2 gene may affect inner ear development and structural integrity and thus might predispose to the onset of MD. As there was a significant difference in onset between the patients, an accumulation of defects in several pathways is probably responsible for the exceptionally early onset of the disease, and the genetic etiology of childhood‐onset MD is most likely multifactorial. This is the first molecular genetic study of childhood‐onset MD. [ABSTRACT FROM AUTHOR]

Movement disorders are increasingly being recognized as a manifestation of childhood-onset mitochondrial diseases (MDs). However, the spectrum and characteristics of these conditions have not been studied in detail in the context of a well-defined cohort of patients. We retrospectively explored a cohort of individuals with childhood-onset MDs querying the Nationwide Italian Collaborative Network of Mitochondrial Diseases database. Using a customized online questionnaire, we attempted to collect data from the subgroup of patients with movement disorders. Complete information was available for 102 patients. Movement disorder was the presenting feature of MD in 45 individuals, with a mean age at onset of 11 years. Ataxia was the most common movement disorder at onset, followed by dystonia, tremor, hypokinetic disorders, chorea, and myoclonus. During the disease course, most patients (67.7%) encountered a worsening of their movement disorder. Basal ganglia involvement, cerebral white matter changes, and cerebellar atrophy were the most commonly associated neuroradiological patterns. Forty-one patients harbored point mutations in the mitochondrial DNA, 10 carried mitochondrial DNA rearrangements, and 41 cases presented mutations in nuclear-DNA-encoded genes, the latter being associated with an earlier onset and a higher impairment in activities of daily living. Among our patients, 32 individuals received pharmacological treatment; clonazepam and oral baclofen were the most commonly used drugs, whereas levodopa and intrathecal baclofen administration were the most effective. A better delineation of the movement disorders phenotypes starting in childhood may improve our diagnostic workup in MDs, fine tuning management, and treatment of affected patients.

Background: Approximately 15–20% cases of systemic lupus erythematosus (SLE) are diagnosed in children. There have been a few studies reporting the epidemiological data of pediatric-onset SLE (cSLE) in China, neither comparing the differences between cSLE and adult-onset SLE (aSLE). The aim of this study was to describe the impact of age of onset on clinical features and survival in cSLE patients in China based on the Chinese SLE Treatment and Research group (CSTAR) database. Methods: We made a prospective study of 225 cSLE patients (aged < 16 years) and 1759 patients aged 16–50 years based on CSTAR registry. We analyzed initial symptoms, clinical presentations, SLE disease activity, damages, and outcomes of cSLE, as well as compared with aSLE patients. Results: The mean age of cSLE patients was 12.16 ± 2.92 years, with 187 (83.1%) females. Fever (P < 0.001) as well as mucocutaneous (P < 0.001) and renal (P = 0.006) disorders were found to be significantly more frequent in cSLE patients as initial symptoms, while muscle and joint lesions were significantly less common compared to aSLE subjects (P < 0.001). The cSLE patients were found to present more frequently with malar rash (P = 0.001; odds ratio [OR], 0.624; 95% confidence interval [CI], 0.470–0.829) but less frequently with arthritis (P < 0.001; OR, 2.013; 95% CI, 1.512–2.679) and serositis (P = 0.030; OR, 1.629; 95% CI, 1.053–2.520). There was no significant difference in SLE disease activity index scores between cSLE and aSLE groups (P = 0.478). Cox regression indicated that childhood onset was the risk factor for organ damage in lupus patients (hazard ratio 0.335 [0.170–0.658], P = 0.001). The survival curves between the cSLE and aSLE groups had no significant difference as determined by the log-rank test (0.557, P = 0.455). Conclusions: cSLE in China has different clinical features and more inflammation than aSLE patients. Damage may be less in children and there is no difference in 5- year survival between cSLE and aSLE groups.

The incidence of childhood-onset Basedow's (Graves') disease is approximately 5% of all cases. Herein, we report a teenage female patient diagnosed with childhood-onset Graves' disease immediately following general anesthesia. Her signs and symptoms included tachycardia immediately prior to general anesthesia, delirium upon emerging from anesthesia, persistent postoperative tachycardia and anxiety, and prolonged nausea and vomiting. [ABSTRACT FROM AUTHOR]

Atopic eczema is one of the most prevalent diseases worldwide. It is a common dermatological disorder that affects 17.8 million individuals in the USA, up to 20% of children and up to 3% of adults. Recent data show that the incidence of the disease is still rising, both in children and adults, especially in low-income countries. Atopic dermatitis in adults consists of childhood-onset (COAD) and adult or late-onset types (LOAD). Prior research has described differences in clinical features, laboratory data, and response to treatment between COAD and LOAD. Most studies have been done on an ambulatory population that mostly contains patients with mild to moderate disease.Objective: The aim of the study was to describe the differences between adults hospitalized with COAD and LOAD.Methods: Data were analyzed from a retrospective cohort of 107 adult AD patients who were hospitalized from 2009 to 2017. Analysis of data included epidemiology, clinical and laboratory characteristics, and response to treatment.Results: Of the total sample, 87 (81%) patients were diagnosed with LOAD, and 20 (19%) patients were diagnosed with COAD. The median age was 66 years for all patients, 42 years for COAD patients, and 77 years for LOAD patients. The prevalence of atopy was lower in the LOAD group than in the COAD group (33.8 vs. 68.8% for family history, 35.5 vs. 84.8% for personal history). A higher incidence of head, neck, and flexural involvement was found in COAD patients. LOAD patients had lower immunoglobulin E levels and responded better to phototherapy.Conclusions: Elderly patients with LOAD constitute the majority of adults hospitalized with AD. As in ambulatory AD patients, there are significant differences in medical background, clinical picture, laboratory characteristics, and response to treatment between hospitalized LOAD and COAD patients. There is a need to determine diagnostic criteria and treatment guidelines for these patients. [ABSTRACT FROM AUTHOR]

Background: The risk factors for rapid growth and early metastasis of papillary thyroid carcinoma (PTC) and the role of coexisting Graves' disease in the clinical course of PTC remain uncertain in children. Case Description: We report on a Japanese girl, whose PTC rapidly grew and metastasized within 4 years. Graves' disease was diagnosed by the presence of serum TSH receptor antibodies at 8 years of age when thyroid ultrasonography detected no nodules. After 4 years of effective treatment with thiamazole, multifocal nodules – up to 47 mm in diameter – were detected on thyroid ultrasonography. Chest CT scan revealed multiple metastatic lesions in the lung. After total thyroidectomy, PTC was pathologically diagnosed. The patient underwent two courses of radioactive iodine (RAI) treatment, but the pulmonary metastatic lesions did not take up the RAI. Molecular analyses of the PTC tissue identified a TFG/NTRK1 chimeric gene and disclosed the preserved expression of TSHR and the reduced expression of SLC5A5 compared with non-tumor thyroid tissue. Conclusions: Rapid growth and early metastasis of PTC with coexisting Graves' disease in this patient can be related to a combination of multiple factors including preserved TSHR expression, reduced SLC5A5 expression, and TFG/NTRK1 rearrangement. [ABSTRACT FROM AUTHOR]

Summary: Objective: Parental depression significantly impacts children's health and well‐being. This study aimed to (1) estimate the prevalence of depressive symptoms, at six time points, among mothers over the first 10 years after their child was diagnosed with epilepsy; (2) identify trajectories of maternal depressive symptoms over time; and (3) identify baseline factors associated with each trajectory. Methods: Data came from the Health‐Related Quality of Life in Children with Epilepsy Study (HERQULES), a Canada‐wide prospective cohort study. Data on child, parent, and family characteristics were collected at the time of diagnosis, and follow‐ups at 0.5, 1, 2, 8, and 10 years. Maternal depressive symptoms were measured using the Center for Epidemiological Studies Depression Scale. Trajectories of depressive symptoms were evaluated using latent class growth modeling, and multinomial logistic regression was used to identify baseline factors associated with each trajectory. Results: A total of 356 mothers participated in the study, of whom 57% scored in the at‐risk range for major depression disorder (period‐prevalence). Four unique trajectories were identified as follows: "Low‐Stable" (29% of mothers), "Intermediate‐Stable" (46%), "High‐Stable" (20%), and "High‐Decreasing" (5%). Positive family environment was consistently associated with a better trajectory of depressive symptoms over time; other significant factors included type of seizures, child cognitive comorbidity, maternal age, and maternal education. Significance: A substantial proportion of mothers of children with epilepsy are at risk for depression, and this risk is stable over the long term. Family environment at the time of diagnosis has long‐term and persistent effects and may be an ideal target for interventions. [ABSTRACT FROM AUTHOR]

Background: Dystonia is a relatively common feature of spinocerebellar ataxia 3 (SCA3). Childhood onset of SCA3 is rare and typically associated with either relatively large, or homozygous, CAG repeat expansions. Case report: We describe a 10-year-old girl with SCA3, who presented with tongue dystonia in addition to limb dystonia and gait ataxia due to a heterozygous expansion of 84 repeats in ATXN3. Discussion: Diagnosis of the SCAs can be challenging, and even more so in children. Tongue dystonia has not previously been documented in SCA3. [ABSTRACT FROM AUTHOR]

Schizophrenia occurs very uncommonly in children younger than 13 years. The disease is preceded by premorbid difficulties, familial vulnerability, and a prodromal phase. The occurrence of positive psychotic symptoms such as delusions and hallucinations depends on the level of cognitive development of child. Furthermore, at times it is very difficult to differentiate the psychopathology and sustain a diagnosis of schizophrenia in view of similarities with disorders such as autism, mood disorders, and obsessive compulsive disorders. Here, we present three case studies with varying presentation of childhood‑onset psychosis/schizophrenia and associated management issues. [ABSTRACT FROM AUTHOR]

Aim Nephrotic syndrome is the most common childhood glomerular disorder, but data on the associated complications are limited and predisposing risk factors have not been fully defined. The aim of this study was to evaluate disease- and treatment-related acute and chronic complications in patients with childhood idiopathic nephrotic syndrome (INS), and to identify the risk factors involved in the development of complications. Methods This single-center study was performed at the pediatric nephrology department of a tertiary pediatric hospital in Turkey. The study included 411 patients with a diagnosis of childhood INS, 128 of whom had disease-related and treatment-related complications. Patients diagnosed and followed-up between January 2010 and January 2022 were evaluated retrospectively. Results Complications occurred in 31.1% of the 411 patients. Mean age at the time of diagnosis was 7.54 ± 4.37 years, and the male/female ratio was 0.9:1. Among the patients with complications, 96.9% were disease-related, and 50.8% were treatment-related complications. In older age, high proteinuria level, a low estimated glomerular filtration rate (eGFR) level at diagnosis, and female gender were significant risk factors for complication development (P = 0.000, P = 0.006, P = 0.04, and P = 0.07, respectively). Chronic kidney disease (CKD) developed in 7% of patients and 2.9% of patients had end-stage renal disease (ESRD). Additionally, three of 12 patients with progressive ESRD underwent transplantation. Also the incidence of ESRD was significantly higher in the patients with complications than in those without complications (P < 0.05). Conclusion The present findings suggest that careful monitoring of patients with childhood INS at risk for complications and implementation of personalized treatment programs can improve long-term outcomes, especially in patients that progress to ESRD and are followed-up with dialysis or transplantation as targeted therapy., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2023, Karakaya et al.)

Abstract: Objectives: A high incidence of Axis II personality disorders is described in patients with bipolar disorder; however, their relationship to mood state remains uncertain. Methods: A total of 966 outpatients with bipolar disorder gave informed consent and filled out the Personality Disorder Questionnaire, 4th edition (PDQ4) and a questionnaire on demographics and course of illness prior to Bipolar Treatment Outcome Network entry at average age 41 years. Patients were rated at each visit for depression on the Inventory of Depressive Symptoms‐Clinician version (IDS‐C) and for mania on the Young Mania Rating Scale (YMRS). In a subgroup, the PDQ4 was retaken during periods of depression and euthymia. Results: Patients met criteria for most personality disorders at a much higher rate when they took the PDQ4 while depressed compared to while euthymic, and scores were significantly related to the severity of depression (IDS) and of mania (YMRS) assessed within 2 weeks of taking the PDQ. Even when euthymic, more than quarter to half of the patients met criteria for a cluster A, B or C personality disorder. Conclusions: A wide range of personality disorders occur in bipolar patients, but are highly dependent on filling out the form while depressed compared to while euthymic. How this relates to having a personality disorder assessed using a structured clinical interview remains to be tested. However, higher PDQ4 scores are related to an earlier age of onset of bipolar disorder and other factors portending a more difficult course of bipolar disorder, and the optimal treatment of these patients remains to be illuminated. [ABSTRACT FROM AUTHOR]

Objectives This systematic review aimed to 1) describe the quality of life (QOL) of parents of children with childhood-onset epilepsy (CWE), 2) identify factors associated with parental QOL, and 3) evaluate the association between parents' QOL and children's psychological well-being. Methods We conducted a comprehensive search of MEDLINE, EMBASE, and PsycINFO and conducted forward and backward citation tracking. A total of 15 articles met inclusion criteria. Parents' QOL was compared with population norms, healthy controls, and parents of children with other chronic conditions. Factors associated with parental QOL were systematically evaluated. Results Heterogeneity in study design and reporting prevented a meta-analytic synthesis of results. The majority of studies found that parents of CWE had poorer QOL relative to healthy controls or population norms and similar QOL as parents of children with other chronic conditions. In addition, poorer parental QOL was consistently associated with greater parental anxiety and depressive symptoms and poorer socioeconomic status and child QOL. Mothers had poorer QOL relative to fathers. Seizure control was not consistently associated with parental QOL. Results highlight the impact of family environment and psychosocial factors. Significance This review suggests that parents of CWE have compromised QOL. The results are in line with previous research showing the interdependent nature of psychosocial and medical factors, with psychosocial factors playing a critical role in child and parental QOL and well-being. Interventions targeting the family unit are warranted, and healthcare providers should be aware of the bidirectional relationship of epilepsy, family environment, and child/parent health and well-being. [ABSTRACT FROM AUTHOR]

Purpose: Epilepsy in childhood extends far beyond seizures and affects child and parental well-being. The long-term impact of childhood-onset epilepsy on parental well-being is unknown. This study assessed health-related quality of life (HRQOL) in mothers 10 years after their child's diagnosis of epilepsy.Methods: Data come from the Health-Related Quality of Life in Children with Epilepsy Study, a multicenter prospective cohort study of children with newly diagnosed epilepsy. Mothers completed a mailed questionnaire at the 10-year follow-up, which included the Short-Form Health Survey (SF-12-v2) to evaluate the physical and mental health components of their HRQOL. Block-wise linear regressions identified child/epilepsy, maternal/family, and maternal psychosocial factors associated with mothers' HRQOL.Results: A total of 159 mothers participated in this study (46% of the sample assessed at baseline). At follow-up, 69% of youth had been seizure free for the past 5 years. Mothers scored similarly to population norms (mean: 50, SD: 10) on the mental health subscale (mean: 49.5, SD: 9.3) and significantly better on the physical health subscale (mean: 53.0, SD: 7.6). Better family resources were associated with higher (better) scores on the physical health subscale (B = 0.20; 95% CI 0.03, 0.36). Better family functioning (B = 0.34; 95% CI 0.06, 0.62), fewer maternal depressive symptoms (B = 0.33; 95% CI 0.20, 0.47), and perception of less stress (B = 0.70; 95% CI 0.52, 0.88) were associated with higher (better) scores on the mental health subscale.Conclusion: Ten years after the diagnosis of epilepsy in children, the HRQOL of mothers was similar to reports from women in the general population. This study identified factors contributing to better maternal HRQOL and highlights the importance of family environment over epilepsy-related variables. [ABSTRACT FROM AUTHOR]

Background: Although growth hormone deficiency (GHD) is an important issue in pediatric patients, adult GHD (AGHD) is a neglected field of endocrinology in China. The aim of this study is to characterize the clinical, hormonal, and radiological features in childhood-onset AGHD (CO AGHD) in a single center in China and to compare them with counterparts from Japan. Methods: The medical records of 78 Chinese patients with CO AGHD were reviewed and compared with data from the HypoCCS database study from Japan (N = 69). Results: The majority of our patients had pituitary stalk interruption, while hypothalamo-pituitary tumors were the most common cause of CO AGHD in Japan. Chinese patients had a lag of 6 years for diagnosis. The majority of both groups had multiple pituitary hormone deficiencies. Body mass index and lipid profiles were similar between the 2 patient groups. Dyslipidemia and hyperuricemia were the most common metabolic disturbances in Chinese patients. Conclusions: Our findings confirm that there are possible regional differences in the etiology, metabolic characteristics, and hormonal status in CO AGHD patients in different countries in Asia. [ABSTRACT FROM AUTHOR]

Background Information on long-term follow up of childhood-onset anorexia nervosa is scarce. This study investigated long-term (>10 years) course, outcome and prognostic factors for hospitalized childhood-onset anorexia nervosa restricting type ( ANR). Methods Forty-one ANR girls admitted to a single regional center participated. Median age at first admission was 13.3 years (range, 8.6-15.6 years). The longitudinal clinical course was retrospectively determined for a median follow-up period of 17.1 years (range, 10.4-21.1 years). We analyzed physical, psychological, and social variables to predict partial remission ( PR) and full remission ( FR). Results The completion rate of follow up >10 years was high at 97%. At final evaluation ( n = 38), distribution of prognosis was as follows: FR, n = 27 (71%); PR, n = 6 (16%); and non-remission, n = 5 (13%). The cumulative ratio of PR and FR increased during the first 5-6 years, and gradually reached a plateau at around 10 years. More than 10 years after the onset, one patient eventually achieved FR, and one patient died. Seven patients were rehospitalized and two died due to suicide during the entire follow up. On multivariate analysis, family disorders/problems rating score was a significant predictor of PR and FR. Conclusions This study included hospitalized ANR children aged ≤15 years, the youngest cohort ever reported. Long-term prognosis is generally favorable, but the mortality rate was 5%. Careful long-term follow up >10 years is needed to evaluate outcome of childhood-onset ANR, and family therapy is important in high-risk patients with family disorders/problems. [ABSTRACT FROM AUTHOR]

Asthma that starts in adulthood differs from childhood-onset asthma in that it is often non-atopic, more severe and associated with a faster decline in lung function. Understanding of the underlying mechanism of adult-onset asthma and identification of specific phenotypes may further our understanding of pathophysiology and treatment response, leading to better targeting of both existing and new approaches for personalised management. Pivotal studies in past years have led to sustained progress in many areas, ranging from risk factors for development, identification of different phenotypes, and introduction of new therapies. This review highlights and discusses literature on adult-onset asthma, with special focus on the differences from childhood-onset asthma, risk factors for development, phenotypes of adult-onset asthma and new approaches for personalised management.

Basal ganglia stroke secondary to mineralizing angiopathy of lenticulostriate arteries is a well-recognized clinical entity following minor head trauma in children. Recurrences are uncommon, and the majority of these recurrences occur within a few months of initial insult. We report a 2-year-old boy who developed recurrence of basal ganglia stroke after a latency of 18 months from the time of first unrecognized insult at 6 months of age. The case brings forth the need to recognize the condition of basal ganglia stroke secondary to mineralizing angiopathy considering the risk of recurrence to occur as far as 18 months after the first stroke. [ABSTRACT FROM AUTHOR]

The individual profiled here (M.S.) suffered an episode of severe oxygen deprivation (anoxia) at the age of eight, damaging memory relevant structures in the mid-temporal lobes, including the hippocampus bilaterally. The resulting anterograde amnesia was characterized by profound deficits in autobiographical memory, but also a compromised ability to acquire new facts and information (semantic memory), resulting in the formation of idiosyncratic and naïve beliefs about the natural world that have persisted into his adult years. This article presents an interview with M.S. in which many of these idiosyncratic beliefs are detailed, and argues that they can be broadly viewed as the interaction of; 1) intact frontal lobe functioning that supports the application of rational analysis to his lived experience, and 2) an impoverished factual knowledge base upon which to construct sophisticated and evidence-based models of his lived experience and of natural world processes. [ABSTRACT FROM AUTHOR]

Background Suicide attempts are common in patients with bipolar disorder (BD), and consistently associated with female gender and certain unfavorable BD illness characteristics. Findings vary, however, regarding effects of BD illness subtype and yet other illness characteristics upon prior suicide attempt rates. We explored the effects of demographics and BD illness characteristics upon prior suicide attempt rates in patients stratified by BD illness subtype (i.e., with bipolar I disorder (BDI) versus bipolar II disorder (BDII)). Methods Outpatients referred to the Stanford BD Clinic during 2000–2011 were assessed with the Systematic Treatment Enhancement Program for BD Affective Disorders Evaluation. Rates of prior suicide attempt were compared in patients with and without diverse demographic and BD illness characteristics stratified by BD subtype. Results Among 494 BD outpatients (mean ± SD age 35.6 ± 13.1 years; 58.3% female; 48.6% BDI, 51.4% BDII), overall prior suicide attempt rates in were similar in BDI versus BDII patients, but approximately twice as high in BDI (but not BDII) patients with compared to without lifetime eating disorder, and in BDII (but not BDI) patients with compared to without childhood BD onset. In contrast, current threshold-level suicidal ideation and lifetime alcohol use disorder robustly but less asymmetrically increased prior suicide attempt risk across BD subtypes. Limitations American tertiary bipolar disorder clinic referral sample, cross-sectional design. Conclusions Further studies are needed to assess the extent to which varying clinical characteristics of samples of patients with BDI and BDII could yield varying prior suicide attempt rates in patients with BDI versus BDII. [ABSTRACT FROM AUTHOR]

Primary brain calcification (PBC) is a neurodegenerative disorder characterized by idiopathic calcification of the basal ganglia that is rare in children and adolescents. This report describes a 16-year-old boy who complained of progressive walking difficulty and gait disturbance for 3 years. Physical examination showed positive reaction to ankle clonus and increased deep tendon reflex on both legs. There was no family history of metabolic disorder or neurologic diseases. Brain computed tomography (CT) and brain magnetic resonance imaging (MRI) revealed extensive calcifications in the bilateral cerebral white matter, basal ganglia, thalamus and dentate nucleus of the cerebellum. Laboratory and genetic studies showed nothing of note. This case report describes an unusual case of sporadic primary brain calcification, diagnosed in adolescence by the presence of gait difficulty and mild mental retardation and its review. [ABSTRACT FROM AUTHOR]

Objective: It remains unclear whether very early onset psychosis (VEOP; ≤12years of age) and early onset psychosis (EOP; onset 13-17years of age) are homogeneous in their clinical presentation. We investigated the predictive value of age of psychosis onset for severity, functioning and demographic variation by: 1) comparing groups based on traditional cut-offs for age of psychosis onset, and 2) using receiver operating characteristic (ROC)-curve calculations, without a priori age of onset cut-offs.Method: Participants were 88 (45 female, 43 male) children and adolescents with a recent onset of psychosis (age range=6.7-17.5years; M=13.74, SD=2.37).Results: The VEOP group had significantly shorter duration of untreated illness and untreated psychosis, and lower functioning than the EOP group. The VEOP and EOP groups did not differ significantly on gender proportion, urbanicity, psychotic diagnosis, family history of psychotic disorder, psychotic, depressive and anxiety symptoms or IQ. When applying ROC-curves to the lowest three quartiles of positive psychotic symptoms scores, the optimal age-cut-off was 14.0years (sensitivity=0.62; specificity=0.75). For the highest quartile of functioning scores, the optimal differentiating cut-off for age of psychosis onset was 14.7years (sensitivity=0.71; specificity=0.70).Conclusions: Larger samples of patients, assessed at presentation and followed-up, are necessary to clearly examine clinical presentation and outcome as a function of social and neural development to better understand if the differentiation between VEOP and EOP is justified. This will aid the development of predictive diagnostic tools, more accurate prognosis prediction, and age-tailored therapeutic interventions. [ABSTRACT FROM AUTHOR]