Explore the vast range of titles available.

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.

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: 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/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: 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.

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.

Background and Objectives: Chromosomal microarray offers superior sensitivity for identification of submicroscopic copy number variants (CNVs) and is recommended for the initial genetic testing of patients with autism spectrum disorder (ASD). This study aims to determine the diagnostic yield of array comparative genomic hybridization (array-CGH) in ASD patients from a cohort of Chinese patients in Taiwan. Materials and Methods: Enrolled in this study were 80 ASD children (49 males and 31 females; 2–16 years old) followed up at Taipei MacKay Memorial Hospital between January 2010 and December 2020. The genomic DNA extracted from blood samples was analyzed by array-CGH via the Affymetrix GeneChip Genome-Wide Human single nucleotide polymorphism (SNP) and NimbleGen International Standards for Cytogenomic Arrays (ISCA) Plus Cytogenetic Arrays. The CNVs were classified into five groups: pathogenic (pathologic variant), likely pathogenic (potential pathologic variant), likely benign (potential normal genomic variant), benign (normal genomic variant), and uncertain clinical significance (variance of uncertain significance), according to the American College of Medical Genetics (ACMG) guidelines. Results: We identified 47 CNVs, 31 of which in 27 patients were clinically significant. The overall diagnostic yield was 33.8%. The most frequently clinically significant CNV was 15q11.2 deletion, which was present in 4 (5.0%) patients. Conclusions: In this study, a satisfactory diagnostic yield of array-CGH was demonstrated in a Taiwanese ASD patient cohort, supporting the clinical usefulness of array-CGH as the first-line testing of ASD in Taiwan.

Mucopolysaccharidosis type IVA (MPS IVA or Morquio A) is an autosomal recessive disorder and is one of the lysosomal storage diseases. Patients with MPS IVA have a striking skeletal phenotype but normal intellect. The phenotypic continuum of MPS IVA ranges from severe and rapid progress to mild and slow progress. The diagnosis of MPS IVA is usually suspected based on abnormal bone findings and dysplasia on physical examination and radiographic investigation in the preschool years. In the past, only supportive care was available. Due to the early and severe skeletal abnormalities, the orthopedic specialist was usually the main care provider. However, patients need aggressive monitoring and management of their systemic disease. Therefore, they need an interdisciplinary team for their care, comprising medical geneticists, cardiologists, pulmonary specialists, gastroenterologists, otolaryngologists, audiologists, and ophthalmologists. After the US Food and Drug Administration approved elosulfase alfa in 2014, patients older than 5 years could benefit from this treatment. Clinical trials showed clinically meaningful improvements with once-a-week intravenous dosing (2.0 mg/kg per week), significantly improving the 6min walk test, the 3min stair climb test, and respiratory function when compared with placebo. Elosulfase alfa is well-tolerated, and there is a good response indicated by decreasing urine glycosaminoglycans.

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.