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Muscle biopsy has long been regarded as the cornerstone for diagnosing pediatric muscular disorders; however, it is invasive and may be limited by sampling error and inconclusive histopathological findings. This study aimed to evaluate whether whole-exome sequencing (WES) can effectively replace muscle biopsy as a first-line diagnostic approach in children with suspected neuromuscular disorders. Between January 2018 and December 2025, we prospectively enrolled 47 pediatric patients presenting with clinical features suggestive of muscular disorders at a tertiary medical center in Taiwan. The cohort included patients with suspected muscular dystrophies (n = 21), congenital myopathies (n = 23), and multiplex ligation-dependent probe amplification (MLPA)-negative Duchenne muscular dystrophy (DMD; n = 3). All patients underwent WES as the initial diagnostic test without prior muscle biopsy. Trio-based analysis using parental samples was performed in 29.8% of cases. Variant interpretation followed the American College of Medical Genetics and Genomics (ACMG) guidelines. WES identified a definitive molecular diagnosis in 72.3% of patients (34/47). Diagnostic yields varied by subgroup: 100% (3/3) in MLPA-negative DMD, 71.4% (15/21) in muscular dystrophies, and 69.6% (16/23) in congenital myopathies. Pathogenic or likely pathogenic variants were detected in 31 distinct genes, including COL6A1 and COL6A3, which are associated with Ullrich congenital muscular dystrophy. Notably, 58.8% of diagnosed patients (20/34) received molecular diagnoses that differed from their initial clinical impression, encompassing conditions such as ZSWIM6-associated neurodevelopmental disorders, GJB2-related hearing loss, OCRL-associated Lowe syndrome, and various metabolic or syndromic disorders. In all three MLPA-negative DMD cases, WES identified point mutations amenable to mutation-specific therapies. No patient required a muscle biopsy for diagnostic confirmation during the study period. First-tier WES demonstrates high diagnostic utility in pediatric muscular disorders while avoiding invasive muscle biopsy. The high rate of diagnostic reclassification underscores the substantial phenotypic overlap between primary neuromuscular diseases and other neurological or systemic conditions. These findings support the early implementation of genetic testing to enable accurate diagnosis and timely initiation of targeted therapies.

Mucopolysaccharidosis (MPS) is a lysosomal storage disease caused by genetic defects that result in deficiency of one specific enzyme activity, consequently impairing the stepwise degradation of glycosaminoglycans (GAGs). Except for MPS II, the other types of MPS have autosomal recessive inheritance in which two copies of an abnormal allele must be present in order for the disease to develop. In this study, we present the status of variant alleles and biochemistry results found in infants suspected of having MPS I, II, IVA, and VI. A total of 324 suspected infants, including 12 for MPS I, 223 for MPS II, 72 for MPS IVA, and 17 for MPS VI, who were referred for MPS confirmation from newborn screening centers in Taiwan, were enrolled. In all of these infants, one specific enzyme activity in dried blood spot filter paper was lower than the cut-off value in the first blood sample, as well asin a second follow-up sample. The confirmatory methods used in this study included Sanger sequencing, next-generation sequencing, leukocyte enzyme fluorometric assay, and GAG-derived disaccharides in urine using tandem mass spectrometry assays. The results showed that five, nine, and six infants had MPS I, II, and IVA, respectively, and all of them were asymptomatic. Thus, a laboratory diagnosis is extremely important to confirm the diagnosis of MPS. The other infants with identified nucleotide variations and reductions in leukocyte enzyme activities were categorized as being highly suspected cases requiring long-term and intensive follow-up examinations. In summary, the final confirmation of MPS depends on the most powerful biomarkers found in urine, i.e., the quantification of GAG-derived disaccharides including dermatan sulfate, heparan sulfate, and keratan sulfate, and analysis of genetic variants can help predict outcomes and guide treatment.

Weaver syndrome is a rare congenital overgrowth disorder caused by pathogenic EZH2 variants. This study reports a novel EZH2 variant associated with atypical manifestations, including severe bilateral camptodactyly and complex brain malformations. A 4-year-old Taiwanese female exhibited classical Weaver syndrome features including macrosomia, macrocephaly, hypertelorism, and developmental delay, plus atypical findings of severe bilateral camptodactyly and complex brain malformations. Neuroimaging revealed corpus callosum dysgenesis with rostral agenesis and genu hypoplasia, bilateral frontal lobe hypoplasia, and an arachnoid cyst. The patient demonstrated global developmental delay with marked motor impairment but less severely affected speech and cognition, consistent with mild intellectual disability. Whole-exome sequencing identified a novel de novo pathogenic variant in EZH2: c.449T>C (p.Ile150Thr), affecting a highly conserved amino acid within the SANT domain. This case broadens the clinical spectrum of Weaver syndrome by highlighting severe camptodactyly and complex brain malformations as possible EZH2-related manifestations. The corpus callosum dysgenesis suggests a wider role of EZH2 in neurodevelopment than previously recognized. The novel SANT domain variant may explain the severe phenotypic presentation. The novel EZH2 variant c.449T>C (p.Ile150Thr) expands the molecular and phenotypic spectrum of Weaver syndrome. These findings underscore the importance of comprehensive neuroimaging and molecular genetic testing in suspected cases, particularly atypical presentations.

Background/Objectives: Mucopolysaccharidosis (MPS) is a group of progressive lysosomal storage disorders affecting multiple organ systems. Although newborn screening enables early detection, early comprehensive imaging assessment during pre-symptomatic stages remains poorly understood. This study analyzed skeletal radiographic and cardiac and abdominal ultrasonographic findings in infants diagnosed by newborn screening to establish an integrated imaging assessment model. Methods: This retrospective study examined 277 screen-positive cases (15 MPS I, 113 MPS II, 127 MPS IVA, and 22 MPS VI) identified through newborn screening between 2015 and 2024. All patients underwent standardized skeletal radiography and cardiac and abdominal ultrasonography. Imaging findings were analyzed in conjunction with biochemical markers and clinical parameters. Results: Cardiac abnormalities were most prevalent in MPS I (33.3% ASD/PFO), whereas vertebral changes were more common in MPS IVA (16.5%) and MPS II (15.9%). We observed a number of significant correlations: vertebral abnormalities correlated with keratan sulfate levels, cardiac manifestations with dermatan sulfate levels, and abdominal findings with enzyme activity levels and urinary dimethylene blue ratios. Conclusions: This systematic analysis of multiple imaging modalities in infants diagnosed with MPS by newborn screening demonstrates that significant abnormalities can be detected during the presymptomatic stage. Correlations between imaging findings and biochemical markers provide new insights for early diagnosis and monitoring, and support implementing comprehensive imaging protocols during the initial screen-positive cases evaluation.

Background/Objectives: Achondroplasia is the most common skeletal dysplasia, affecting 1 in 25,000 births. Limited research exists on the assessment of functional independence using standardized tools in children and adolescents with achondroplasia. The WeeFIM scale provides a comprehensive evaluation of daily living skills across multiple functional domains. This study aimed to assess the functional independence levels in children and adolescents with achondroplasia using WeeFIM and analyze functional capabilities. Methods: This multicenter cross-sectional study included 46 participants aged 6–18 years with confirmed achondroplasia. Data were collected through standardized WeeFIM assessments from medical centers and online surveys (2021–2024). WeeFIM evaluates 18 functional items across 3 domains: self-care (8 items), mobility (5 items), and cognition (5 items), scored 1–7 (complete dependence to independence). Results: Participants included 26 males (56.5%) and 20 females (43.5%). Most (78.3%) were diagnosed during infancy. The mean functional scores were highest for cognition (34.0/35, 97.1%), followed by self-care (51.2/56, 91.4%) and mobility (31.5/35, 90.0%). Most participants achieved near-complete independence in cognitive functions. Mobility tasks, particularly stair climbing and bathtub transfers, showed the greatest challenges. Functional independence increased with age, with significant improvements during early childhood to adolescence transition. Conclusions: Children and adolescents with achondroplasia demonstrate high functional independence across daily activities, with cognitive abilities largely unaffected. Although specific mobility challenges exist, most participants achieve independence with appropriate accommodations. These findings provide valuable baseline data for clinical care planning and support optimistic functional outcomes for pediatric patients with achondroplasia.

Background: Silver–Russell syndrome (SRS) is a genetic disorder characterized by prenatal and postnatal growth retardation. Affected individuals commonly present with low birth weight, intrauterine growth restriction, postnatal short stature, hemihypotrophy, characteristic facial features, and body asymmetry. Methods: This study includes 24 Taiwanese children with SRS aged 2 years to 13 years and 3 months who were recruited at MacKay Memorial Hospital and other Taiwan hospitals between January 2013 and December 2024. Functional independence was assessed using the Functional Independence Measure for Children (WeeFIM) to evaluate self-care, mobility, and cognition domains. Results: The mean total WeeFIM score was 106.9 ± 23.2 (range: 54–126), with mean self-care, mobility, and cognition scores of 44.4 ± 13.8 (maximum 56), 32.4 ± 5.1 (maximum 35), and 30.2 ± 6.0 (maximum 35), respectively. The results of the restricted cubic spline analysis reveal a clear positive linear correlation before school age (approximately 72 months), followed by a plateau (p for nonlinearity < 0.05). Traceable molecular data were available for thirteen participants, of whom nine (69%) had loss of methylation at chromosome 11p15 (11p15LOM), and four (31%) had maternal uniparental disomy of chromosome 7 (upd(7)mat). Of the 24 children, 46% required assistance with bathing, which was strongly correlated with self-care ability and body height. In contrast, most of the children had independence in mobility tasks such as walking and stair climbing. However, some required support in cognitive tasks, including problem-solving, comprehension, and expression. Overall, the included children reached a functional plateau later than the normative population, with the greatest delays in self-care and mobility domains. Conclusions: This study highlights that Taiwanese children with SRS require support in self-care and cognitive tasks. Functional independence in self-care and mobility domains was positively associated with body height. The WeeFIM questionnaire effectively identified strengths and limitations, emphasizing the need for individualized support in daily activities.

Objective To investigate the prevalence and epidemiological characteristics of primary palmar hyperhidrosis (PPH) among adolescents in PR China. Methods A nationwide survey was performed, including all seven geological areas of Mainland China. Stratified cluster sampling was performed, and a cross-sectional epidemiological survey was applied via questionnaire among 10,000 college students in each geological area. Results The prevalence rate of PPH was 2.08 %. The prevalence in female adolescents was slightly higher than the prevalence in male adolescents (2.29 vs. 1.94 %). The prevalence of PPH in coastal areas was higher than the prevalence of PPH in inland areas (2.81 vs. 1.53 %). The peak age of onset is 7–15 years, accounting for 97.3 % of the PPH population. Positive family history was found in 25.40 % of PPH cases. In addition to palms, axillae and soles can also be affected. Conclusions PPH affects a larger group of individuals than previously reported. More measures should be taken to enhance the recognition, diagnosis, and treatment of PPH.

Background and Clinical Significance: Mucopolysaccharidosis type VII (MPS VII), an ultrarare lysosomal storage disorder caused by β-glucuronidase deficiency, presents significant therapeutic challenges. Given its extreme rarity and limited treatment experience in Asian populations, documenting long-term treatment outcomes is crucial for advancing clinical knowledge and improving patient care. Case Presentation: We report a 3-year follow-up of enzyme replacement therapy (ERT) in the first Taiwanese case of MPS VII. The patient, who initially presented with hydrops fetalis and developmental delay, was diagnosed at age 4 through genetic analysis, which revealed compound heterozygous variants of c.104C > A (p.Ser35Ter) and c.1454C > T (p.Ser485Phe) on the GUSB gene. ERT with vestronidase alfa was initiated at age 6. During the follow-up period, significant clinical improvements were observed, including elimination of oxygen dependency, with BiPAP needed only during sleep; changes in mobility, with 6-min walk test distance showing an initial decline from 130 to 70 m followed by partial recovery to 95 m after multiple orthopedic surgeries; and steady progression of growth parameters showed, with height increasing from 110 to 118 cm. Urinary glycosaminoglycan (GAG) levels measured by dimethylmethylene blue spectrophotometry decreased and stabilized. The patient’s cardiac and hepatic conditions remained stable, although splenomegaly persisted. No severe adverse events were reported during ERT. Conclusions: This case demonstrates the effectiveness and safety of long-term ERT in MPS VII, particularly in improving respiratory function and physical performance. Our experience highlights the importance of early diagnosis and treatment initiation, while providing valuable insights into the management of this ultrarare disease in the Asian population.

Background: Lesch–Nyhan syndrome (LNS) is a rare X-linked recessive metabolic disorder caused by mutations in the HPRT1 gene, resulting in hypoxanthine–guanine phosphoribosyltransferase (HPRT) deficiency. Early diagnosis is critical for optimizing management and improving outcomes. This study presents a case series of three Taiwanese patients diagnosed at a single medical center. Methods: Exome sequencing and biochemical testing were used to confirm the diagnoses. Early clinical manifestations, including hyperuricemia, hypotonia, and developmental delay, were documented during the initial stages of the disease. Results: All three patients had hyperuricemia, hypotonia, spasticity, and motor developmental delay. Pathogenic variants in the HPRT1 gene were identified in two patients, while the third was confirmed by biochemical testing. Two patients had orange-colored crystalline deposits in their diapers, indicative of hyperuricosuria. Self-injurious behavior had not yet developed in two patients due to their young age. Conclusions: Early clinical features such as hyperuricemia, hypotonia, and motor delay may suggest LNS in infancy. Molecular genetic testing, particularly whole exome sequencing, can facilitate an early diagnosis before specific manifestations occur, enabling timely interventions and improving patient outcomes.

Kabuki syndrome (KS) is a rare genetic disorder characterized by distinct facial features, intellectual disability, and multiple congenital anomalies. We conducted a comprehensive analysis of the genetic and phenotypic spectrum of KS in a Taiwanese patient group of 23 patients. KMT2D variants were found in 22 individuals, with missense (26.1%), nonsense (21.7%), and frameshift (17.4%) variants being the most prevalent. One patient had a KMT2D variant of uncertain significance. The most common clinical characteristics included distinct facial features (100%), intellectual disability (100%), developmental delay (95.7%), speech delay (78.3%), hypotonia (69.6%), congenital heart abnormalities (69.6%), and recurrent infections (65.2%). Other abnormalities included hearing loss (39.1%), seizures (26.1%), cleft palate (26.1%), and renal anomalies (21.7%). This study broadens the mutational and phenotypic spectrum of KS in the Taiwanese population, highlighting the importance of comprehensive genetic testing and multidisciplinary clinical evaluations for diagnosis and treatment.