Early‐onset bradykinetic rigid syndrome and reflex seizures in a child with PURA syndrome

Abstract

PURA syndrome is a distinct form of developmental encephalopathy, characterized by early-onset hypotonia, severe developmental delay, intellectual disability, epilepsy and respiratory and gastrointestinal disorders. We report a child with PURA syndrome, harbouring a previously described mutation, whose phenotype included two peculiar aspects: (1) hypokinetic-rigid syndrome, which was part of the clinical presentation from an early stage of the disease, and (2) reflex seizures, consisting of a series of spasms. We provide detailed clinical description and video recordings demonstrating both these aspects that are newly described in PURA syndrome. The early clinical features described here may therefore be included in the complex phenotype associated with PURA gene mutations and may help in the early diagnosis of patients. Furthermore, PURA syndrome should be considered in the differential diagnosis of early-onset bradykinetic rigid syndromes.

Expanding the phenotype of PURA‐related developmental epileptic encephalopathy

“…However, the observation of an early‐onset bradykinetic syndrome by Solazzi et al . [1] is indeed a novel finding, not reported previously. In their patient, hypo/bradykinesia was observed at the age of 11 months, associated with limb rigidity, hypomimia and severe global developmental delay.…”

“…In conclusion, the paper by Solazzi et al . [1] adds novel features to the phenotypic spectrum of PURA‐related DEE, possibly contributing to an early diagnosis that should ultimately prompt referral of the patients for genetic testing. Furthermore, it highlights the usefulness and need for detailed “deep” phenotyping studies of complex DEEs, not only for more precise and timely diagnosis, but also to ultimately identify genotype‐phenotype correlations, at present lacking in PURA‐related DEE, and reconstruct the natural history of this condition.…”

“…In the series of Solazzi et al [1] and in about 18% of the series of Johannesen et al [3], the clinical picture featured both reflex seizures and a startle response to acoustic stimuli, suggesting that diffuse cortical hyperxcitability might contribute to the pathophysiology of both phenomena, similarly to what has been hypothesized for other forms of genetic encephalopathies, such as encephalopathy associated with pathogenic KCNQ2 variants which can display exaggerated startle attacks in 38% of individuals [11]. In conclusion, the paper by Solazzi et al [1] adds novel features to the phenotypic spectrum of PURA-related DEE, possibly contributing to an early diagnosis that should ultimately prompt referral of the patients for genetic testing. Furthermore, it highlights the usefulness and need for detailed "deep" phenotyping studies of complex DEEs, not only for more precise and timely diagnosis, but also to ultimately identify genotype-phenotype correlations, at present lacking in PURA-related DEE, and reconstruct the natural history of this condition.…”

“…Interestingly, in some patients, a reflex mechanism was observed only for a transitory period, raising the issue of a possible under-estimation of this phenomenon, particularly in those subjects presenting with very frequent seizures, non-epileptic motor disorders and severe intellectual disability. In the series of Solazzi et al [1] and in about 18% of the series of Johannesen et al [3], the clinical picture featured both reflex seizures and a startle response to acoustic stimuli, suggesting that diffuse cortical hyperxcitability might contribute to the pathophysiology of both phenomena, similarly to what has been hypothesized for other forms of genetic encephalopathies, such as encephalopathy associated with pathogenic KCNQ2 variants which can display exaggerated startle attacks in 38% of individuals [11]. In conclusion, the paper by Solazzi et al [1] adds novel features to the phenotypic spectrum of PURA-related DEE, possibly contributing to an early diagnosis that should ultimately prompt referral of the patients for genetic testing.…”

“…To the Editor, We have read with great interest the report by Solazzi et al (Early-onset bradykinetic rigid syndrome and reflex seizures in a child with PURA syndrome. Epileptic Disord 2021; 23: 745-8) [1] who describe a previously unreported child affected by PURA-related developmental and epileptic encephalopathy (PURArelated DEE) harbouring a known pathogenic variant, whose phenotype included two peculiar features, i.e. onset of hypokinetic-rigid syndrome at an early age and reflex seizures.…”