Background: De novo mutations in the GABBR2 (Gamma-Aminobutyric acid Type B Receptor Subunit 2) gene have recently been reported to be associated with a form of early-infantile epileptic encephalopathy (EIEE59; OMIM# 617904), as well as a Rett syndrome (RTT)-like disorder defined as a neurodevelopmental disorder with poor language and loss of hand skills (NDPLHS; OMIM# 617903). Methods: We describe a pediatric case carrying a de novo GABBR2 pathogenic variant and showing a phenotype encompassing RTT, epilepsy, generalized hypotonia with a paroxysmal limb dystonia. Results: A 11-year-old girl, born to non-consanguineous parents after an uneventful pregnancy, had developmental delay and generalized hypotonia. At age 3.5 months she presented with infantile spasms with an electroencephalographic pattern of hypsarrhythmia. After treatment with clonazepam and prednisolone, she became seizure-free with a slow background electrical activity. Brain magnetic resonance imaging was normal. Paroxysmal dystonic posturing of the extremities, especially the upper limbs, have been observed since the age of 3 years. Motor stereotypies, non-epileptic episodes of hyperventilation and breath-holding were also reported. The girl suffered from feeding difficulties requiring gastrostomy at the age of 8. Exome sequencing (ES) revealed a de novo GABBR2 pathogenic variant (NM_005458:c.G2077T:p.G693W). Conclusion: Paroxysmal limb dystonias, especially in the context of neurodevelopmental disorder featuring epilepsy, generalized hypotonia and RTT-like features should lead to the suspect of GABBR2 mutations.

Paroxysmal limb dystonias associated with GABBR2 pathogenic variant: A case-based literature review

D'Onofrio G.;Cali' E.;Accogli A.;Zara F.;Striano P.;
2022

Abstract

Background: De novo mutations in the GABBR2 (Gamma-Aminobutyric acid Type B Receptor Subunit 2) gene have recently been reported to be associated with a form of early-infantile epileptic encephalopathy (EIEE59; OMIM# 617904), as well as a Rett syndrome (RTT)-like disorder defined as a neurodevelopmental disorder with poor language and loss of hand skills (NDPLHS; OMIM# 617903). Methods: We describe a pediatric case carrying a de novo GABBR2 pathogenic variant and showing a phenotype encompassing RTT, epilepsy, generalized hypotonia with a paroxysmal limb dystonia. Results: A 11-year-old girl, born to non-consanguineous parents after an uneventful pregnancy, had developmental delay and generalized hypotonia. At age 3.5 months she presented with infantile spasms with an electroencephalographic pattern of hypsarrhythmia. After treatment with clonazepam and prednisolone, she became seizure-free with a slow background electrical activity. Brain magnetic resonance imaging was normal. Paroxysmal dystonic posturing of the extremities, especially the upper limbs, have been observed since the age of 3 years. Motor stereotypies, non-epileptic episodes of hyperventilation and breath-holding were also reported. The girl suffered from feeding difficulties requiring gastrostomy at the age of 8. Exome sequencing (ES) revealed a de novo GABBR2 pathogenic variant (NM_005458:c.G2077T:p.G693W). Conclusion: Paroxysmal limb dystonias, especially in the context of neurodevelopmental disorder featuring epilepsy, generalized hypotonia and RTT-like features should lead to the suspect of GABBR2 mutations.
File in questo prodotto:
Non ci sono file associati a questo prodotto.

I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/11567/1090568
 Attenzione

Attenzione! I dati visualizzati non sono stati sottoposti a validazione da parte dell'ateneo

Citazioni
  • ???jsp.display-item.citation.pmc??? 0
  • Scopus 0
  • ???jsp.display-item.citation.isi??? 0
social impact