Case Report: Clinical delineation of CACNA1D mutation: New cases and literature review
BackgroundCalcium ions are involved in several human cellular processes; nevertheless, the relationship between calcium channelopathies (CCs) and autism spectrum disorder (ASD) or intellectual disability (ID) has been previously investigated. We delineate the spectrum of clinical phenotypes and the...
| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2023-04-01
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| Series: | Frontiers in Neurology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fneur.2023.1131490/full |
| _version_ | 1797847227398356992 |
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| author | Alshaimaa Alzahrani Maha Alshalan Mohammed Alfurayh Abdulaziz Bin Akrish Najlaa A. Alsubeeh Fuad Al Mutairi Fuad Al Mutairi |
| author_facet | Alshaimaa Alzahrani Maha Alshalan Mohammed Alfurayh Abdulaziz Bin Akrish Najlaa A. Alsubeeh Fuad Al Mutairi Fuad Al Mutairi |
| author_sort | Alshaimaa Alzahrani |
| collection | DOAJ |
| description | BackgroundCalcium ions are involved in several human cellular processes; nevertheless, the relationship between calcium channelopathies (CCs) and autism spectrum disorder (ASD) or intellectual disability (ID) has been previously investigated. We delineate the spectrum of clinical phenotypes and the symptoms associated with a syndrome caused by an inherited gain-of-function mutation in CACNA1D in a family with a history of neuropsychiatric disorders. We also review the clinical and molecular phenotype of previously reported variants of CACNA1D.Case presentationWe report the case of a 9-year-old female patient, diagnosed with ASD, severe ID, hyperactivity, and aggressive impulsive behaviors. The father, who was a 65-year-old at the time of his death, had ID and developed major depressive disorder with catatonic features and nihilistic delusion, followed by rapidly progressive dementia. He died after experiencing prolonged seizures followed by post-cardiac arrest. The patient’s sister was a 30-year-old woman, known to have a severe ID with aggressive behaviors and sleep disorders. The sister has been diagnosed with bipolar disorder and psychosis. Through whole exome sequencing, a heterozygous previously identified and functionally characterized missense likely pathogenic variant was identified in the CACNA1D gene NM_001128840.3: c.2015C > T (p.Ser672Leu). These findings are consistent with the genetic diagnosis of autosomal dominant primary aldosteronism, seizures, and neurological abnormalities. This variant was found in the heterozygous status in the patient, her father, and her affected sister.ConclusionThis case report will help to determine the key clinical features of this syndrome, which exhibits variable clinical presentations. |
| first_indexed | 2024-04-09T18:07:55Z |
| format | Article |
| id | doaj.art-7031d07d400a4fdc9017f3283953b37c |
| institution | Directory Open Access Journal |
| issn | 1664-2295 |
| language | English |
| last_indexed | 2024-04-09T18:07:55Z |
| publishDate | 2023-04-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Neurology |
| spelling | doaj.art-7031d07d400a4fdc9017f3283953b37c2023-04-14T05:23:15ZengFrontiers Media S.A.Frontiers in Neurology1664-22952023-04-011410.3389/fneur.2023.11314901131490Case Report: Clinical delineation of CACNA1D mutation: New cases and literature reviewAlshaimaa Alzahrani0Maha Alshalan1Mohammed Alfurayh2Abdulaziz Bin Akrish3Najlaa A. Alsubeeh4Fuad Al Mutairi5Fuad Al Mutairi6Genetic and Precision Medicine Department, King Abdullah Specialized Children Hospital, King Abdulaziz Medical City, Ministry of National Guard Health Affairs (MNGHA), Riyadh, Saudi ArabiaGenetic and Precision Medicine Department, King Abdullah Specialized Children Hospital, King Abdulaziz Medical City, Ministry of National Guard Health Affairs (MNGHA), Riyadh, Saudi ArabiaCollege of Medicine, King Saud Bin Abdulaziz University for Health Sciences, Riyadh, Saudi ArabiaCollege of Medicine, King Saud Bin Abdulaziz University for Health Sciences, Riyadh, Saudi ArabiaGenetic and Precision Medicine Department, King Abdullah Specialized Children Hospital, King Abdulaziz Medical City, Ministry of National Guard Health Affairs (MNGHA), Riyadh, Saudi ArabiaGenetic and Precision Medicine Department, King Abdullah Specialized Children Hospital, King Abdulaziz Medical City, Ministry of National Guard Health Affairs (MNGHA), Riyadh, Saudi ArabiaKing Abdullah International Medical Research Center (KAIMRC), King Saud Bin Abdulaziz University for Health Sciences, Ministry of National Guard Health Affairs (MNGHA), Riyadh, Saudi ArabiaBackgroundCalcium ions are involved in several human cellular processes; nevertheless, the relationship between calcium channelopathies (CCs) and autism spectrum disorder (ASD) or intellectual disability (ID) has been previously investigated. We delineate the spectrum of clinical phenotypes and the symptoms associated with a syndrome caused by an inherited gain-of-function mutation in CACNA1D in a family with a history of neuropsychiatric disorders. We also review the clinical and molecular phenotype of previously reported variants of CACNA1D.Case presentationWe report the case of a 9-year-old female patient, diagnosed with ASD, severe ID, hyperactivity, and aggressive impulsive behaviors. The father, who was a 65-year-old at the time of his death, had ID and developed major depressive disorder with catatonic features and nihilistic delusion, followed by rapidly progressive dementia. He died after experiencing prolonged seizures followed by post-cardiac arrest. The patient’s sister was a 30-year-old woman, known to have a severe ID with aggressive behaviors and sleep disorders. The sister has been diagnosed with bipolar disorder and psychosis. Through whole exome sequencing, a heterozygous previously identified and functionally characterized missense likely pathogenic variant was identified in the CACNA1D gene NM_001128840.3: c.2015C > T (p.Ser672Leu). These findings are consistent with the genetic diagnosis of autosomal dominant primary aldosteronism, seizures, and neurological abnormalities. This variant was found in the heterozygous status in the patient, her father, and her affected sister.ConclusionThis case report will help to determine the key clinical features of this syndrome, which exhibits variable clinical presentations.https://www.frontiersin.org/articles/10.3389/fneur.2023.1131490/fullcase reportCACNA1D geneautism (ASC)pervasive development disorderchildhood neurologic disordersseizure |
| spellingShingle | Alshaimaa Alzahrani Maha Alshalan Mohammed Alfurayh Abdulaziz Bin Akrish Najlaa A. Alsubeeh Fuad Al Mutairi Fuad Al Mutairi Case Report: Clinical delineation of CACNA1D mutation: New cases and literature review Frontiers in Neurology case report CACNA1D gene autism (ASC) pervasive development disorder childhood neurologic disorders seizure |
| title | Case Report: Clinical delineation of CACNA1D mutation: New cases and literature review |
| title_full | Case Report: Clinical delineation of CACNA1D mutation: New cases and literature review |
| title_fullStr | Case Report: Clinical delineation of CACNA1D mutation: New cases and literature review |
| title_full_unstemmed | Case Report: Clinical delineation of CACNA1D mutation: New cases and literature review |
| title_short | Case Report: Clinical delineation of CACNA1D mutation: New cases and literature review |
| title_sort | case report clinical delineation of cacna1d mutation new cases and literature review |
| topic | case report CACNA1D gene autism (ASC) pervasive development disorder childhood neurologic disorders seizure |
| url | https://www.frontiersin.org/articles/10.3389/fneur.2023.1131490/full |
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