The epilepsy phenotype of ST3GAL3‐related developmental and epileptic encephalopathy
Abstract Objective ST3GAL3‐related developmental and epileptic encephalopathy (DEE‐15) is an autosomal recessive condition characterized by intellectual disability, language and motor impairments, behavioral difficulties, stereotypies, and epilepsy. Only a few cases have been reported, and the epile...
| Main Authors: | , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Wiley
2023-06-01
|
| Series: | Epilepsia Open |
| Subjects: | |
| Online Access: | https://doi.org/10.1002/epi4.12747 |
| _version_ | 1797813827124854784 |
|---|---|
| author | Robyn Whitney Puneet Jain Rajesh RamachandranNair Kevin C. Jones Hassan Kiani Mark Tarnopolsky Brandon Meaney |
| author_facet | Robyn Whitney Puneet Jain Rajesh RamachandranNair Kevin C. Jones Hassan Kiani Mark Tarnopolsky Brandon Meaney |
| author_sort | Robyn Whitney |
| collection | DOAJ |
| description | Abstract Objective ST3GAL3‐related developmental and epileptic encephalopathy (DEE‐15) is an autosomal recessive condition characterized by intellectual disability, language and motor impairments, behavioral difficulties, stereotypies, and epilepsy. Only a few cases have been reported, and the epilepsy phenotype is not fully elucidated. Methods A retrospective chart review of two siblings with ST3GAL3‐related DEE was completed. In addition, we reviewed all published cases of ST3GAL3‐related congenital disorder of glycosylation. Results Two brothers presented with global developmental delay, motor and language impairment, hypotonia, and childhood‐onset seizures. Seizures started between 2.5 and 5 years and had tonic components. Both siblings had prolonged periods of seizure freedom on carbamazepine. Tremor was present in the younger sibling. Whole exome sequencing revealed two novel pathogenic variants in ST3GAL3, (a) c.302del, p.Phe102Serfs*34 and (b) c.781C>T, p.Arg261*, which were inherited in trans. Magnetic resonance imaging showed T2 hyperintensities and restricted diffusion in the brainstem and middle cerebellar peduncle in the older sibling, also described in two reported cases. A review of the literature revealed 24 cases of ST3GAL3‐related CDG. Twelve cases had information about seizures, and epilepsy was diagnosed in 8 (67%). The median age of seizure onset was 5.5 months. Epileptic spasms were most common (67%). Four children were diagnosed with Infantile Epileptic Spasms syndrome and Lennox Gastaut syndrome (57%). Most children (n = 6, 75%) had seizures despite anti‐seizure medication treatment. Significance Seizures related to ST3GAL3‐related DEE often occur in infancy and may present as epileptic spasms. However, seizure onset may also occur outside of infancy with mixed seizure types and show good response to treatment with prolonged seizure freedom. Tremor may also be uniquely observed in this condition. |
| first_indexed | 2024-03-13T07:58:26Z |
| format | Article |
| id | doaj.art-c83a2b715f8a4f6eb4d18639673abe15 |
| institution | Directory Open Access Journal |
| issn | 2470-9239 |
| language | English |
| last_indexed | 2024-03-13T07:58:26Z |
| publishDate | 2023-06-01 |
| publisher | Wiley |
| record_format | Article |
| series | Epilepsia Open |
| spelling | doaj.art-c83a2b715f8a4f6eb4d18639673abe152023-06-02T03:50:17ZengWileyEpilepsia Open2470-92392023-06-018262363210.1002/epi4.12747The epilepsy phenotype of ST3GAL3‐related developmental and epileptic encephalopathyRobyn Whitney0Puneet Jain1Rajesh RamachandranNair2Kevin C. Jones3Hassan Kiani4Mark Tarnopolsky5Brandon Meaney6Division of Neurology Department of Paediatrics McMaster University Hamilton Ontario CanadaEpilepsy Program Division of Neurology Department of Paediatrics Hospital for Sick Children University of Toronto Toronto Ontario CanadaDivision of Neurology Department of Paediatrics McMaster University Hamilton Ontario CanadaDivision of Neurology Department of Paediatrics McMaster University Hamilton Ontario CanadaDivision of Neurology Department of Paediatrics McMaster University Hamilton Ontario CanadaDivision of Neuromuscular and Neurometabolic Disorders Department of Paediatrics McMaster University Hamilton Ontario CanadaDivision of Neurology Department of Paediatrics McMaster University Hamilton Ontario CanadaAbstract Objective ST3GAL3‐related developmental and epileptic encephalopathy (DEE‐15) is an autosomal recessive condition characterized by intellectual disability, language and motor impairments, behavioral difficulties, stereotypies, and epilepsy. Only a few cases have been reported, and the epilepsy phenotype is not fully elucidated. Methods A retrospective chart review of two siblings with ST3GAL3‐related DEE was completed. In addition, we reviewed all published cases of ST3GAL3‐related congenital disorder of glycosylation. Results Two brothers presented with global developmental delay, motor and language impairment, hypotonia, and childhood‐onset seizures. Seizures started between 2.5 and 5 years and had tonic components. Both siblings had prolonged periods of seizure freedom on carbamazepine. Tremor was present in the younger sibling. Whole exome sequencing revealed two novel pathogenic variants in ST3GAL3, (a) c.302del, p.Phe102Serfs*34 and (b) c.781C>T, p.Arg261*, which were inherited in trans. Magnetic resonance imaging showed T2 hyperintensities and restricted diffusion in the brainstem and middle cerebellar peduncle in the older sibling, also described in two reported cases. A review of the literature revealed 24 cases of ST3GAL3‐related CDG. Twelve cases had information about seizures, and epilepsy was diagnosed in 8 (67%). The median age of seizure onset was 5.5 months. Epileptic spasms were most common (67%). Four children were diagnosed with Infantile Epileptic Spasms syndrome and Lennox Gastaut syndrome (57%). Most children (n = 6, 75%) had seizures despite anti‐seizure medication treatment. Significance Seizures related to ST3GAL3‐related DEE often occur in infancy and may present as epileptic spasms. However, seizure onset may also occur outside of infancy with mixed seizure types and show good response to treatment with prolonged seizure freedom. Tremor may also be uniquely observed in this condition.https://doi.org/10.1002/epi4.12747congenital disorder of glycosylationdevelopmental and epileptic encephalopathygeneticsgenotypeST3GAL3 |
| spellingShingle | Robyn Whitney Puneet Jain Rajesh RamachandranNair Kevin C. Jones Hassan Kiani Mark Tarnopolsky Brandon Meaney The epilepsy phenotype of ST3GAL3‐related developmental and epileptic encephalopathy Epilepsia Open congenital disorder of glycosylation developmental and epileptic encephalopathy genetics genotype ST3GAL3 |
| title | The epilepsy phenotype of ST3GAL3‐related developmental and epileptic encephalopathy |
| title_full | The epilepsy phenotype of ST3GAL3‐related developmental and epileptic encephalopathy |
| title_fullStr | The epilepsy phenotype of ST3GAL3‐related developmental and epileptic encephalopathy |
| title_full_unstemmed | The epilepsy phenotype of ST3GAL3‐related developmental and epileptic encephalopathy |
| title_short | The epilepsy phenotype of ST3GAL3‐related developmental and epileptic encephalopathy |
| title_sort | epilepsy phenotype of st3gal3 related developmental and epileptic encephalopathy |
| topic | congenital disorder of glycosylation developmental and epileptic encephalopathy genetics genotype ST3GAL3 |
| url | https://doi.org/10.1002/epi4.12747 |
| work_keys_str_mv | AT robynwhitney theepilepsyphenotypeofst3gal3relateddevelopmentalandepilepticencephalopathy AT puneetjain theepilepsyphenotypeofst3gal3relateddevelopmentalandepilepticencephalopathy AT rajeshramachandrannair theepilepsyphenotypeofst3gal3relateddevelopmentalandepilepticencephalopathy AT kevincjones theepilepsyphenotypeofst3gal3relateddevelopmentalandepilepticencephalopathy AT hassankiani theepilepsyphenotypeofst3gal3relateddevelopmentalandepilepticencephalopathy AT marktarnopolsky theepilepsyphenotypeofst3gal3relateddevelopmentalandepilepticencephalopathy AT brandonmeaney theepilepsyphenotypeofst3gal3relateddevelopmentalandepilepticencephalopathy AT robynwhitney epilepsyphenotypeofst3gal3relateddevelopmentalandepilepticencephalopathy AT puneetjain epilepsyphenotypeofst3gal3relateddevelopmentalandepilepticencephalopathy AT rajeshramachandrannair epilepsyphenotypeofst3gal3relateddevelopmentalandepilepticencephalopathy AT kevincjones epilepsyphenotypeofst3gal3relateddevelopmentalandepilepticencephalopathy AT hassankiani epilepsyphenotypeofst3gal3relateddevelopmentalandepilepticencephalopathy AT marktarnopolsky epilepsyphenotypeofst3gal3relateddevelopmentalandepilepticencephalopathy AT brandonmeaney epilepsyphenotypeofst3gal3relateddevelopmentalandepilepticencephalopathy |