Characteristics of Developmental and Epileptic Encephalopathy Associated with <i>PACS2</i> p.Glu209Lys Pathogenic Variant—Our Experience and Systematic Review of the Literature
Background: Developmental and epileptic encephalopathies (DEE) encompass a group of rare diseases with hereditary and genetic causes as well as acquired causes such as brain injuries or metabolic abnormalities. The phosphofurin acidic cluster sorting protein 2 (PACS2) is a multifunctional protein wi...
| Main Authors: | , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2024-02-01
|
| Series: | Biomolecules |
| Subjects: | |
| Online Access: | https://www.mdpi.com/2218-273X/14/3/270 |
| _version_ | 1797241868001476608 |
|---|---|
| author | Adina Stoian Zoltan Bajko Rodica Bălașa Sebastian Andone Mircea Stoian Ioana Ormenișan Carmen Muntean Claudia Bănescu |
| author_facet | Adina Stoian Zoltan Bajko Rodica Bălașa Sebastian Andone Mircea Stoian Ioana Ormenișan Carmen Muntean Claudia Bănescu |
| author_sort | Adina Stoian |
| collection | DOAJ |
| description | Background: Developmental and epileptic encephalopathies (DEE) encompass a group of rare diseases with hereditary and genetic causes as well as acquired causes such as brain injuries or metabolic abnormalities. The phosphofurin acidic cluster sorting protein 2 (PACS2) is a multifunctional protein with nuclear gene expression. The first cases of the recurrent c.625G>A pathogenic variant of <i>PACS2</i> gene were reported in 2018 by Olson et al. Since then, several case reports and case series have been published. Methods: We performed a systematic review of the PUBMED and SCOPUS databases using Preferred Reporting Items for Systematic Review and Meta-Analyses (PRISMA) guidelines. Our search parameters included DEE66 with a pathogenic <i>PACS2</i> gene p.Glu209Lys mutation published cases to which we added our own clinical experience regarding this pathology. Results: A total of 11 articles and 29 patients were included in this review, to which we added our own experience for a total of 30 patients. There was not a significant difference between sexes regarding the incidence of this pathology (M/F: 16/14). The most common neurological and psychiatric symptoms presented by the patients were: early onset epileptic seizures, delayed global development (including motor and speech delays), behavioral disturbances, limited intellectual capacity, nystagmus, hypotonia, and a wide-based gait. Facial dysmorphism and other organs’ involvement were also frequently reported. Brain MRIs evidenced anomalies of the posterior cerebellar fossa, foliar distortion of the cerebellum, vermis hypoplasia, white matter reduction, and lateral ventricles enlargement. Genetic testing is more frequent in children. Only 4 cases have been reported in adults to date. Conclusions: It is important to maintain a high suspicion of new pathogenic gene variants in adult patients presenting with a characteristic clinical picture correlated with radiologic changes. The neurologist must gradually recognize the distinct evolving phenotype of DEE66 in adult patients, and genetic testing must become a scenario with which the neurologist attending adult patients should be familiar. Accurate diagnosis is required for adequate treatment, genetic counseling, and an improved long-term prognosis. |
| first_indexed | 2024-04-24T18:30:09Z |
| format | Article |
| id | doaj.art-7eb2fbfb7e3243179995c0d836571eec |
| institution | Directory Open Access Journal |
| issn | 2218-273X |
| language | English |
| last_indexed | 2024-04-24T18:30:09Z |
| publishDate | 2024-02-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Biomolecules |
| spelling | doaj.art-7eb2fbfb7e3243179995c0d836571eec2024-03-27T13:27:49ZengMDPI AGBiomolecules2218-273X2024-02-0114327010.3390/biom14030270Characteristics of Developmental and Epileptic Encephalopathy Associated with <i>PACS2</i> p.Glu209Lys Pathogenic Variant—Our Experience and Systematic Review of the LiteratureAdina Stoian0Zoltan Bajko1Rodica Bălașa2Sebastian Andone3Mircea Stoian4Ioana Ormenișan5Carmen Muntean6Claudia Bănescu7Department of Pathophysiology, George Emil Palade University of Medicine, Pharmacy, Science and Technology of Targu Mures, 540139 Targu Mures, RomaniaDepartment of Neurology, George Emil Palade University of Medicine, Pharmacy, Science and Technology of Targu Mures, 540139 Targu Mures, RomaniaDepartment of Neurology, George Emil Palade University of Medicine, Pharmacy, Science and Technology of Targu Mures, 540139 Targu Mures, RomaniaDepartment of Neurology, George Emil Palade University of Medicine, Pharmacy, Science and Technology of Targu Mures, 540139 Targu Mures, RomaniaDepartment of Anesthesia and Intensive Care, George Emil Palade University of Medicine, Pharmacy, Science and Technology of Targu Mures, 540139 Targu Mures, Romania1st Neurology Clinic, Mures County Emergency Hospital, 540142 Targu Mures, RomaniaDepartment of Pediatrics, George Emil Palade University of Medicine, Pharmacy, Science and Technology of Targu Mures, 540142 Targu Mures, RomaniaDepartment of Genetics, George Emil Palade University of Medicine, Pharmacy, Science and Technology of Targu Mures, 540142 Targu Mures, RomaniaBackground: Developmental and epileptic encephalopathies (DEE) encompass a group of rare diseases with hereditary and genetic causes as well as acquired causes such as brain injuries or metabolic abnormalities. The phosphofurin acidic cluster sorting protein 2 (PACS2) is a multifunctional protein with nuclear gene expression. The first cases of the recurrent c.625G>A pathogenic variant of <i>PACS2</i> gene were reported in 2018 by Olson et al. Since then, several case reports and case series have been published. Methods: We performed a systematic review of the PUBMED and SCOPUS databases using Preferred Reporting Items for Systematic Review and Meta-Analyses (PRISMA) guidelines. Our search parameters included DEE66 with a pathogenic <i>PACS2</i> gene p.Glu209Lys mutation published cases to which we added our own clinical experience regarding this pathology. Results: A total of 11 articles and 29 patients were included in this review, to which we added our own experience for a total of 30 patients. There was not a significant difference between sexes regarding the incidence of this pathology (M/F: 16/14). The most common neurological and psychiatric symptoms presented by the patients were: early onset epileptic seizures, delayed global development (including motor and speech delays), behavioral disturbances, limited intellectual capacity, nystagmus, hypotonia, and a wide-based gait. Facial dysmorphism and other organs’ involvement were also frequently reported. Brain MRIs evidenced anomalies of the posterior cerebellar fossa, foliar distortion of the cerebellum, vermis hypoplasia, white matter reduction, and lateral ventricles enlargement. Genetic testing is more frequent in children. Only 4 cases have been reported in adults to date. Conclusions: It is important to maintain a high suspicion of new pathogenic gene variants in adult patients presenting with a characteristic clinical picture correlated with radiologic changes. The neurologist must gradually recognize the distinct evolving phenotype of DEE66 in adult patients, and genetic testing must become a scenario with which the neurologist attending adult patients should be familiar. Accurate diagnosis is required for adequate treatment, genetic counseling, and an improved long-term prognosis.https://www.mdpi.com/2218-273X/14/3/270PACS2brain atrophyneurological regressionepileptic encephalopathydevelopmental and epileptic encephalopathy |
| spellingShingle | Adina Stoian Zoltan Bajko Rodica Bălașa Sebastian Andone Mircea Stoian Ioana Ormenișan Carmen Muntean Claudia Bănescu Characteristics of Developmental and Epileptic Encephalopathy Associated with <i>PACS2</i> p.Glu209Lys Pathogenic Variant—Our Experience and Systematic Review of the Literature Biomolecules PACS2 brain atrophy neurological regression epileptic encephalopathy developmental and epileptic encephalopathy |
| title | Characteristics of Developmental and Epileptic Encephalopathy Associated with <i>PACS2</i> p.Glu209Lys Pathogenic Variant—Our Experience and Systematic Review of the Literature |
| title_full | Characteristics of Developmental and Epileptic Encephalopathy Associated with <i>PACS2</i> p.Glu209Lys Pathogenic Variant—Our Experience and Systematic Review of the Literature |
| title_fullStr | Characteristics of Developmental and Epileptic Encephalopathy Associated with <i>PACS2</i> p.Glu209Lys Pathogenic Variant—Our Experience and Systematic Review of the Literature |
| title_full_unstemmed | Characteristics of Developmental and Epileptic Encephalopathy Associated with <i>PACS2</i> p.Glu209Lys Pathogenic Variant—Our Experience and Systematic Review of the Literature |
| title_short | Characteristics of Developmental and Epileptic Encephalopathy Associated with <i>PACS2</i> p.Glu209Lys Pathogenic Variant—Our Experience and Systematic Review of the Literature |
| title_sort | characteristics of developmental and epileptic encephalopathy associated with i pacs2 i p glu209lys pathogenic variant our experience and systematic review of the literature |
| topic | PACS2 brain atrophy neurological regression epileptic encephalopathy developmental and epileptic encephalopathy |
| url | https://www.mdpi.com/2218-273X/14/3/270 |
| work_keys_str_mv | AT adinastoian characteristicsofdevelopmentalandepilepticencephalopathyassociatedwithipacs2ipglu209lyspathogenicvariantourexperienceandsystematicreviewoftheliterature AT zoltanbajko characteristicsofdevelopmentalandepilepticencephalopathyassociatedwithipacs2ipglu209lyspathogenicvariantourexperienceandsystematicreviewoftheliterature AT rodicabalasa characteristicsofdevelopmentalandepilepticencephalopathyassociatedwithipacs2ipglu209lyspathogenicvariantourexperienceandsystematicreviewoftheliterature AT sebastianandone characteristicsofdevelopmentalandepilepticencephalopathyassociatedwithipacs2ipglu209lyspathogenicvariantourexperienceandsystematicreviewoftheliterature AT mirceastoian characteristicsofdevelopmentalandepilepticencephalopathyassociatedwithipacs2ipglu209lyspathogenicvariantourexperienceandsystematicreviewoftheliterature AT ioanaormenisan characteristicsofdevelopmentalandepilepticencephalopathyassociatedwithipacs2ipglu209lyspathogenicvariantourexperienceandsystematicreviewoftheliterature AT carmenmuntean characteristicsofdevelopmentalandepilepticencephalopathyassociatedwithipacs2ipglu209lyspathogenicvariantourexperienceandsystematicreviewoftheliterature AT claudiabanescu characteristicsofdevelopmentalandepilepticencephalopathyassociatedwithipacs2ipglu209lyspathogenicvariantourexperienceandsystematicreviewoftheliterature |