First Successful Application of Preimplantation Genetic Diagnosis for Lethal Neonatal Rigidity and Multifocal Seizure Syndrome in Korea: A Case Report
Lethal neonatal rigidity and multifocal seizure syndrome (RMFSL) is a severe autosomal recessive epileptic encephalopathy characterized by rigidity, intractable multifocal seizures, microcephaly, apnea, and bradycardia immediately after birth. RMFSL is related to a mutation in breast cancer 1-associ...
| Main Authors: | , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Korean Society of Neonatology
2022-11-01
|
| Series: | Neonatal Medicine |
| Subjects: | |
| Online Access: | http://neo-med.org/upload/pdf/nm-2022-29-4-141.pdf |
| _version_ | 1811199209907421184 |
|---|---|
| author | Gyeong Eun Yeom Young Hwa Jung Soo Yeon Kim Sun Ah Choi Hunmin Kim Chang Won Choi |
| author_facet | Gyeong Eun Yeom Young Hwa Jung Soo Yeon Kim Sun Ah Choi Hunmin Kim Chang Won Choi |
| author_sort | Gyeong Eun Yeom |
| collection | DOAJ |
| description | Lethal neonatal rigidity and multifocal seizure syndrome (RMFSL) is a severe autosomal recessive epileptic encephalopathy characterized by rigidity, intractable multifocal seizures, microcephaly, apnea, and bradycardia immediately after birth. RMFSL is related to a mutation in breast cancer 1-associated ataxia telangiectasia mutated activation-1 protein (BRAT1). We report a case of a female infant born to non-consanguineous Korean parents who developed hypertonia, dysmorphic features, progressive encephalopathy with refractory seizures at birth, and worsening intermittent apnea, leading to intubation and death at 137 days of age. The initial repeated electroencephalographic findings were normal; however, a pattern of focal seizures emerged at 35 days of life. Rapid trio whole-exome sequencing revealed heterozygous mutations c.1313_1314delAG p.(Gln438Argfs*51) and c.1276C>T p. (Gln426*) in BRAT1. After genetic counseling for pregnancy planning, a preimplantation genetic diagnosis for targeted BRAT1 mutations was successfully performed, and a healthy baby was born. To our knowledge, this is the first reported case of a Korean patient with compound heterozygous mutations in BRAT1. An early and accurate genetic diagnosis can help provide timely treatment to patients and indicate the need for reproductive counseling for parents for family planning. |
| first_indexed | 2024-04-12T01:44:11Z |
| format | Article |
| id | doaj.art-8daa259d883e4cb1a80bf52344d33641 |
| institution | Directory Open Access Journal |
| issn | 2287-9412 2287-9803 |
| language | English |
| last_indexed | 2024-04-12T01:44:11Z |
| publishDate | 2022-11-01 |
| publisher | Korean Society of Neonatology |
| record_format | Article |
| series | Neonatal Medicine |
| spelling | doaj.art-8daa259d883e4cb1a80bf52344d336412022-12-22T03:53:07ZengKorean Society of NeonatologyNeonatal Medicine2287-94122287-98032022-11-0129414114810.5385/nm.2022.29.4.1411071First Successful Application of Preimplantation Genetic Diagnosis for Lethal Neonatal Rigidity and Multifocal Seizure Syndrome in Korea: A Case ReportGyeong Eun Yeom0Young Hwa Jung1Soo Yeon Kim2Sun Ah Choi3Hunmin Kim4Chang Won Choi5 Department of Pediatrics, Seoul National University Children’s Hospital, Seoul, Korea Department of Pediatrics, Seoul National University Bundang Hospital, Seongnam, Korea Department of Genomic Medicine, Seoul National University Children’s Hospital, Seoul, Korea Department of Pediatrics, Ewha Womans University Mokdong Hospital, Seoul, Korea Department of Pediatrics, Seoul National University Bundang Hospital, Seongnam, Korea Department of Pediatrics, Seoul National University Bundang Hospital, Seongnam, KoreaLethal neonatal rigidity and multifocal seizure syndrome (RMFSL) is a severe autosomal recessive epileptic encephalopathy characterized by rigidity, intractable multifocal seizures, microcephaly, apnea, and bradycardia immediately after birth. RMFSL is related to a mutation in breast cancer 1-associated ataxia telangiectasia mutated activation-1 protein (BRAT1). We report a case of a female infant born to non-consanguineous Korean parents who developed hypertonia, dysmorphic features, progressive encephalopathy with refractory seizures at birth, and worsening intermittent apnea, leading to intubation and death at 137 days of age. The initial repeated electroencephalographic findings were normal; however, a pattern of focal seizures emerged at 35 days of life. Rapid trio whole-exome sequencing revealed heterozygous mutations c.1313_1314delAG p.(Gln438Argfs*51) and c.1276C>T p. (Gln426*) in BRAT1. After genetic counseling for pregnancy planning, a preimplantation genetic diagnosis for targeted BRAT1 mutations was successfully performed, and a healthy baby was born. To our knowledge, this is the first reported case of a Korean patient with compound heterozygous mutations in BRAT1. An early and accurate genetic diagnosis can help provide timely treatment to patients and indicate the need for reproductive counseling for parents for family planning.http://neo-med.org/upload/pdf/nm-2022-29-4-141.pdfbrat1muscle hypertoniawhole exome sequencingpreimplantation diagnosis |
| spellingShingle | Gyeong Eun Yeom Young Hwa Jung Soo Yeon Kim Sun Ah Choi Hunmin Kim Chang Won Choi First Successful Application of Preimplantation Genetic Diagnosis for Lethal Neonatal Rigidity and Multifocal Seizure Syndrome in Korea: A Case Report Neonatal Medicine brat1 muscle hypertonia whole exome sequencing preimplantation diagnosis |
| title | First Successful Application of Preimplantation Genetic Diagnosis for Lethal Neonatal Rigidity and Multifocal Seizure Syndrome in Korea: A Case Report |
| title_full | First Successful Application of Preimplantation Genetic Diagnosis for Lethal Neonatal Rigidity and Multifocal Seizure Syndrome in Korea: A Case Report |
| title_fullStr | First Successful Application of Preimplantation Genetic Diagnosis for Lethal Neonatal Rigidity and Multifocal Seizure Syndrome in Korea: A Case Report |
| title_full_unstemmed | First Successful Application of Preimplantation Genetic Diagnosis for Lethal Neonatal Rigidity and Multifocal Seizure Syndrome in Korea: A Case Report |
| title_short | First Successful Application of Preimplantation Genetic Diagnosis for Lethal Neonatal Rigidity and Multifocal Seizure Syndrome in Korea: A Case Report |
| title_sort | first successful application of preimplantation genetic diagnosis for lethal neonatal rigidity and multifocal seizure syndrome in korea a case report |
| topic | brat1 muscle hypertonia whole exome sequencing preimplantation diagnosis |
| url | http://neo-med.org/upload/pdf/nm-2022-29-4-141.pdf |
| work_keys_str_mv | AT gyeongeunyeom firstsuccessfulapplicationofpreimplantationgeneticdiagnosisforlethalneonatalrigidityandmultifocalseizuresyndromeinkoreaacasereport AT younghwajung firstsuccessfulapplicationofpreimplantationgeneticdiagnosisforlethalneonatalrigidityandmultifocalseizuresyndromeinkoreaacasereport AT sooyeonkim firstsuccessfulapplicationofpreimplantationgeneticdiagnosisforlethalneonatalrigidityandmultifocalseizuresyndromeinkoreaacasereport AT sunahchoi firstsuccessfulapplicationofpreimplantationgeneticdiagnosisforlethalneonatalrigidityandmultifocalseizuresyndromeinkoreaacasereport AT hunminkim firstsuccessfulapplicationofpreimplantationgeneticdiagnosisforlethalneonatalrigidityandmultifocalseizuresyndromeinkoreaacasereport AT changwonchoi firstsuccessfulapplicationofpreimplantationgeneticdiagnosisforlethalneonatalrigidityandmultifocalseizuresyndromeinkoreaacasereport |