| Dae-Hyun Jang | 8 Articles |
Pediatric rehabilitation
Cerebral palsy (CP) is the most common motor disability in children, characterized by diverse clinical manifestations and often uncertain etiology, which has spurred increasing interest in genetic diagnostics. This review synthesizes findings from various studies to enhance understanding of CP’s genetic underpinnings. The discussion is structured around five key areas: monogenic causes and copy number variants directly linked to CP, differential genetic disorders including atypical CP and mimics, ambiguous genetic influences, co-occurrence with other neurodevelopmental disorders, and polygenic risk factors. Case studies illustrate the clinical application of these genetic insights, underscoring the complexity of diagnosing CP due to the phenotypic overlap with other conditions and the potential for misdiagnosis. The review highlights the significant role of advanced genetic testing in distinguishing CP from similar neurodevelopmental disorders and assessing cases with unclear clinical presentations. Furthermore, it addresses the ongoing challenges in establishing a consensus on genetic contributors to CP, the need for comprehensive patient phenotyping, and the integration of rigorous genetic and functional studies to validate findings. This comprehensive examination of CP genetics aims to pave the way for more precise diagnostics and personalized treatment plans, urging continued research to overcome the current limitations and refine diagnostic criteria within this field.
Vanishing white matter (VWM) disease is an autosomal recessive disorder that affects the central nervous system of a patient, and is caused by the development of pathogenic mutations in any of the EIF2B1-5 genes. Any dysfunction of the EIF2B1-5 gene encoded eIF2B causes stress-provoked episodic rapid neurological deterioration in the patient, followed by a chronic progressive disease course. We present the case of a patient with an infantileonset VWM with the pre-described specific clinical course, subsequent neurological aggravation induced by each viral infection, and the noted consequent progression into a comatose state. Although the initial brain magnetic resonance imaging did not reveal specific pathognomonic signs of VWM to distinguish it from other types of demyelinating leukodystrophy, the next-generation sequencing studies identified heterozygous missense variants in EIF2B3, including a novel variant in exon 7 (C706G), as well as a 0.008% frequency reported variant in exon 2 (T89C). Hence, the characteristic of unbiased genomic sequencing can clinically affect patient care and decisionmaking, especially in terms of the consideration of genetic disorders such as leukoencephalopathy in pediatric patients.
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Patients with a duplication from 7q36 to the terminus or a deletion of 9p24 have been reported, whereas those harboring both mutations have not. Here, we report a patient with simultaneous de novo 7q36.1-q36.3 duplication and 9p24.3 deletion. A 6-year-old boy presented with speech developmental delay, microcephaly, and dysmorphic features, including a long face and small nose. Chromosome and array comparative genomic hybridization analyses revealed 46,XY,dup(7)(q36.1-q36.3) and del(9)(p24.3). The sizes of the duplication and deletion were 9.9 Mb and 1.9 Mb, respectively. The duplication of chromosome 7 contained 68 known genes, of which 3 are related with entries in the Developmental Disorders Genotype-to-Phenotype (DDG2P) database. The deletion of chromosome 9 contained 6 known genes, of which 2 are in the DDG2P database. We investigated the genotype and phenotype in this patient, and reviewed the relevant literatures for possible clinical presentation in these variations. Citations Citations to this article as recorded by
To investigate the factors influencing the development of self-care activity, and the association between mobility and self-care activity in children with cerebral palsy (CP). A total of 63 CP children aged ≥4 years, were studied retrospectively. Children with severe intellectual disability or behavioral problems were excluded. The relationship between the Gross Motor Function Classification System (GMFCS), the Manual Ability Classification System (MACS), and the Pediatric Evaluation of Disability Inventory (PEDI) was analyzed. Simple and multiple linear regression analyses were conducted for continuous variables, such as verbal intelligence quotient (IQ) and PEDI subscales. Final evaluation was done for 25 children, ranging from 4 to 11 years of age. According to GMFCS levels, the differences in PEDI-self-care scores, showed statistically borderline significance (p=0.051). Conversely, differences in PEDI-self-care scores according to CP types and MACS levels were not statistically significant. Simple linear regression analysis showed that PEDI mobility and PEDI social function significantly influence the PEDI self-care. Multiple linear regression analysis showed that PEDI mobility was the only factor significantly influencing PEDI self-care in children aged ≥7 years (R2=0.875, p=0.03). Mobility is important for the acquisition of self-care abilities in children with CP aged ≥7 years. Citations Citations to this article as recorded by
Cerebrotendinous xanthomatosis is a rare autosomal recessive disease that involves multiple organs, including the peripheral nervous system. The present study is the first to report the ultrasonographic findings of peripheral nerves in a patient with cerebrotendinous xanthomatosis. The patient presented with bilateral Achilles tendon enlargement and foot hypesthesia. Sonographic examination revealed hypoechoic, swollen peripheral nerves with enlarged bilateral Achilles tendons. Since the ultrasonographic findings revealed peripheral involvement, the diagnosis of cerebrotendinous xanthomatosis was established after laboratory and genetic studies along with clinical findings. Citations Citations to this article as recorded by
Next-generation sequencing, such as whole-genome sequencing, whole-exome sequencing, and targeted panel sequencing have been applied for diagnosis of many genetic diseases, and are in the process of replacing the traditional methods of genetic analysis. Clinical exome sequencing (CES), which provides not only sequence variation data but also clinical interpretation, aids in reaching a final conclusion with regards to genetic diagnosis. Sequencing of genes with clinical relevance rather than whole exome sequencing might be more suitable for the diagnosis of known hereditary disease with genetic heterogeneity. Here, we present the clinical usefulness of CES for the diagnosis of hereditary spastic paraplegia (HSP). We report a case of patient who was strongly suspected of having HSP based on her clinical manifestations. HSP is one of the diseases with high genetic heterogeneity, the 72 different loci and 59 discovered genes identified so far. Therefore, traditional approach for diagnosis of HSP with genetic analysis is very challenging and time-consuming. CES with TruSight One Sequencing Panel, which enriches about 4,800 genes with clinical relevance, revealed compound heterozygous mutations in Citations Citations to this article as recorded by
To evaluate the clinical differences between patients with diabetes mellitus (DM) who have asymptomatic carpal tunnel syndrome (CTS) and those who have symptomatic CTS. Sixty-three patients with DM were assessed using the Boston Carpal Tunnel Questionnaire (BCTQ), nerve conduction studies (NCS), and ultrasonographic evaluation of the cross-sectional area (CSA) of the median nerve. According to the BCTQ responses and NCS results, the patients were divided into the following three groups: group 1 (n=16), in which NCS results did not reveal CTS; group 2 (n=19), in which NCS results revealed CTS but the group scored 0 points on the BCTQ (asymptomatic); and group 3 (n=28), in which NCS results revealed CTS and the group scored >1 point on the BCTQ (symptomatic). The clinical findings, NCS results, and CSA of the median nerve were compared among the three groups. There were no significant differences in age, DM duration, glycated hemoglobin levels, and presence of diabetic polyneuropathy among the three groups. The peak latency of the median sensory nerve action potential was significantly shorter in group 1 than in groups 2 and 3 (p<0.001); however, no difference was observed between groups 2 and 3. CSA of the median nerve at the carpal tunnel in group 2 was significantly larger than that in group 1 and smaller than that in group 3 (p<0.05). The results of our study suggest that the symptoms of CTS in patients with diabetes are related to CSA of the median nerve, which is consistent with swelling of the nerve. Citations Citations to this article as recorded by
To evaluate the pathophysiological mechanism of hemifacial spasm (HFS), we performed electrophysiological examinations, such as supraorbital nerve stimulation with orbicularis oris muscle recording and lateral spread tests, after suppressing the patient's central nervous system by administering intravenous diazepam. Six patients with HFS were recruited. Supraorbital nerve stimulation with orbicularis oris muscle recording and the lateral spread test were performed, followed by intravenous application of 10 mg diazepam to achieve facial motor neuron suppression. Subsequently, we repeated the two electrophysiological experiments mentioned above at 10 and 20 minutes after the patients had received the diazepam intravenously. Orbicularis oris muscle responses were observed in all patients after supraorbital nerve stimulation and lateral spread tests. After the diazepam injection, no orbicularis oris muscle response to supraorbital nerve stimulation was observed in one patient, and the latencies of this response were evident as a slowing tendency with time in the remaining five patients. However, the latencies of the orbicularis oris muscle responses were observed consistently in all patients in the lateral spread test. Our results suggest that ectopic excitation/ephaptic transmission contributes to the pathophysiological mechanisms of HFS. This is because the latencies of the orbicularis oris muscle responses in the lateral spread test were observed consistently in the suppressed motor neuron in our patients. Citations Citations to this article as recorded by
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