Shedding light on the phenotypic–genotypic correlation of rare treatable and potentially treatable pediatric movement disorders
Abstract Background Advances in genetic science have led to the identification of many rare treatable pediatric movements disorders (MDs). We explored the phenotypic–genotypic spectrum of pediatric patients presenting with MDs. By this, we aimed at raising awareness about such rare disorders, especi...
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| Format: | Article |
| Language: | English |
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SpringerOpen
2022-04-01
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| Series: | Egyptian Journal of Medical Human Genetics |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s43042-022-00286-w |
| _version_ | 1818644989294411776 |
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| author | Dina Amin Saleh Azza Abd El Moneim Attia |
| author_facet | Dina Amin Saleh Azza Abd El Moneim Attia |
| author_sort | Dina Amin Saleh |
| collection | DOAJ |
| description | Abstract Background Advances in genetic science have led to the identification of many rare treatable pediatric movements disorders (MDs). We explored the phenotypic–genotypic spectrum of pediatric patients presenting with MDs. By this, we aimed at raising awareness about such rare disorders, especially in our region. Over the past 3 years, we reviewed the demographic data, clinical profile, molecular genetics and other diagnostic workups of pediatric patients presenting with MDs. Results Twelve patients were identified; however, only six patients were genetically confirmed. The phenomenology of MDs ranged from paroxysmal kinesigenic choreoathetosis (1 patient), exercise-induced dyskinesia (2 patients), ataxia (2 patients) and dystonia (2 patients). Whole-exome sequencing in addition to the functional studies for some patients revealed a specific genetic diagnosis being responsible for their MDs. The genetic diagnosis of our patients included infantile convulsions and paroxysmal choreoathetosis syndrome and episodic ataxia due to “pathogenic homozygous mutation of PRRT2 gene,” glucose transporter type 1 deficiency-exercise induced dyskinesia due to “De Novo pathogenic heterozygous missense mutation of exon 4 of SLC2A1 gene,” aromatic L amino acid decarboxylase deficiency due to “pathogenic homozygous mutation of the DDC gene,” myopathy with extrapyramidal signs due to “likely pathogenic homozygous mutations of the MICU1 gene,” mitochondrial trifunctional protein deficiency due to “homozygous variant of uncertain significance (VUS) of HADHB gene” and glutaric aciduria II with serine deficiency due to “homozygous VUS for both ETFDH and PHGDH genes.” After receiving the treatment as per recognized treatment protocols, two patients showed complete resolution of symptoms and the rest showed variable responses. Conclusion Identifying the genetic etiology of our patients guided us to provide either disease-specific treatment or redirected our management plan. Hence, highlighting the value of molecular genetic analysis to avoid the diagnostic odyssey and identify treatable MDs. |
| first_indexed | 2024-12-17T00:23:36Z |
| format | Article |
| id | doaj.art-40d49acc00c245c89117ba8e421b241c |
| institution | Directory Open Access Journal |
| issn | 2090-2441 |
| language | English |
| last_indexed | 2024-12-17T00:23:36Z |
| publishDate | 2022-04-01 |
| publisher | SpringerOpen |
| record_format | Article |
| series | Egyptian Journal of Medical Human Genetics |
| spelling | doaj.art-40d49acc00c245c89117ba8e421b241c2022-12-21T22:10:31ZengSpringerOpenEgyptian Journal of Medical Human Genetics2090-24412022-04-0123111610.1186/s43042-022-00286-wShedding light on the phenotypic–genotypic correlation of rare treatable and potentially treatable pediatric movement disordersDina Amin Saleh0Azza Abd El Moneim Attia1Department of Pediatrics, Faculty of Medicine, Ain Shams UniversityDepartment of Histology and Cell Biology, Faculty of Medicine, Ain Shams UniversityAbstract Background Advances in genetic science have led to the identification of many rare treatable pediatric movements disorders (MDs). We explored the phenotypic–genotypic spectrum of pediatric patients presenting with MDs. By this, we aimed at raising awareness about such rare disorders, especially in our region. Over the past 3 years, we reviewed the demographic data, clinical profile, molecular genetics and other diagnostic workups of pediatric patients presenting with MDs. Results Twelve patients were identified; however, only six patients were genetically confirmed. The phenomenology of MDs ranged from paroxysmal kinesigenic choreoathetosis (1 patient), exercise-induced dyskinesia (2 patients), ataxia (2 patients) and dystonia (2 patients). Whole-exome sequencing in addition to the functional studies for some patients revealed a specific genetic diagnosis being responsible for their MDs. The genetic diagnosis of our patients included infantile convulsions and paroxysmal choreoathetosis syndrome and episodic ataxia due to “pathogenic homozygous mutation of PRRT2 gene,” glucose transporter type 1 deficiency-exercise induced dyskinesia due to “De Novo pathogenic heterozygous missense mutation of exon 4 of SLC2A1 gene,” aromatic L amino acid decarboxylase deficiency due to “pathogenic homozygous mutation of the DDC gene,” myopathy with extrapyramidal signs due to “likely pathogenic homozygous mutations of the MICU1 gene,” mitochondrial trifunctional protein deficiency due to “homozygous variant of uncertain significance (VUS) of HADHB gene” and glutaric aciduria II with serine deficiency due to “homozygous VUS for both ETFDH and PHGDH genes.” After receiving the treatment as per recognized treatment protocols, two patients showed complete resolution of symptoms and the rest showed variable responses. Conclusion Identifying the genetic etiology of our patients guided us to provide either disease-specific treatment or redirected our management plan. Hence, highlighting the value of molecular genetic analysis to avoid the diagnostic odyssey and identify treatable MDs.https://doi.org/10.1186/s43042-022-00286-wAtaxiaDyskinesiaDystoniaGenotypeMovement disordersPhenotype |
| spellingShingle | Dina Amin Saleh Azza Abd El Moneim Attia Shedding light on the phenotypic–genotypic correlation of rare treatable and potentially treatable pediatric movement disorders Egyptian Journal of Medical Human Genetics Ataxia Dyskinesia Dystonia Genotype Movement disorders Phenotype |
| title | Shedding light on the phenotypic–genotypic correlation of rare treatable and potentially treatable pediatric movement disorders |
| title_full | Shedding light on the phenotypic–genotypic correlation of rare treatable and potentially treatable pediatric movement disorders |
| title_fullStr | Shedding light on the phenotypic–genotypic correlation of rare treatable and potentially treatable pediatric movement disorders |
| title_full_unstemmed | Shedding light on the phenotypic–genotypic correlation of rare treatable and potentially treatable pediatric movement disorders |
| title_short | Shedding light on the phenotypic–genotypic correlation of rare treatable and potentially treatable pediatric movement disorders |
| title_sort | shedding light on the phenotypic genotypic correlation of rare treatable and potentially treatable pediatric movement disorders |
| topic | Ataxia Dyskinesia Dystonia Genotype Movement disorders Phenotype |
| url | https://doi.org/10.1186/s43042-022-00286-w |
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