Background and Objectives:Relative to the pediatric population, there is very limited information about Dravet Syndrome (DS) in adults. In addition to some of the gait abnormalities reported in children with DS (such as crouch gait and ataxia), adults with this condition have other gait and motor disturbances. Our primary objective was to examine gait and motor manifestations in older adults with DS.Methods:This study has a prospective arm where 6 patients (mean age 32-years-old) were examined through a modified version of the Unified Parkinson’s Disease Rating Scale (mUPDRS) in 2014 and again in 2019. mUPDRS scores were assigned to gait, resting tremors, facial expression, arising from a chair, posture, and body bradykinesia. The cross-sectional arm includes mUPDRS testing in patients that were not evaluated in 2014, and an instrumental gait analysis (IGA). These cross-sectional tests were done in the 2019-2020 period. The IGA was performed using the ProtoKinetics software with a gait mat built with sensors and two cameras capturing the sagittal and coronal planes. The IGA was performed in a group of 17 patients with DS (mean age: 31-years-old), the control group consisted of 81 healthy individuals, whose mean age was 62-years-old. Regression analyses were performed for the IGA and mUPDRS data.Results:Five out of six participants evaluated prospectively over 5 years experienced worsening of their parkinsonian manifestations, including gait. Two patients (47 and 51 years old) who were initially ambulatory, could no longer walk 5 years later. The cross-sectional analysis of mUPDRS in a larger group of adults showed that worse scores for arising from a chair (p= 0.04), body bradykinesia (p= 0.01), and gait (p= 0.0003) were positively associated with age. The IGA cross-sectional arm revealed that all 17 adults with DS had abnormal gait parameters in all domains tested. This group of patients performed worse than the healthy and older control group.Discussion:Although seizures may decrease in older adults with DS, this prospective and cross-sectional study showed that their motor symptoms and gait become progressively worse as they age.

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Background: Children with biallelic mutations in TRNT1 have multi-organ involvement with congenital sideroblastic anemia, -B-cell immunodeficiency, periodic fevers, and developmental delay (SIFD) as well as seizures, ataxia and sensorineural hearing loss. The TRNT1 gene encodes the CCA-adding enzyme essential for maturation of both nuclear and mitochondrial transfer RNAs accounting for phenotypic pleitropy. Neurodegenerative Leigh syndrome has not been previously reported. Methods:Case summary: A Portuguese boy presented with global developmental delay, 2 episodes of infantile Leigh encephalopathy at 8 mo and 4 yr responsive to high-dose steroids, slow neurodegeneration of cognitive, language and motor functions with optic atrophy, pigmentary retinopathy, spasticity, dystonia, and focal dyscognitive seizures, pancytopenia, transfusion dependent sideroblastic anemia, recurrent febrile infections (pulmonary, gastrointestinal), hypernatremia, with tracheostomy dependence at age 5 yr, malabsorption and TPN dependence at 9 yr, and survival to early adulthood. Neuroimaging showed symmetric hemorrhagic lesions in the thalamus, brain stem (periaqueductal grey) and cerebellum consistent with Leigh syndrome but no lactate peak on MRS. Results: Whole exome sequencing identified a homozygous missense pathogenic variant in TRNT1, c.668T>C (p.I223T) in the affected individual. Conclusions: This report expands the neurological phenotype of TRNT1 mutations and highlights the importance of considering this gene in the evaluation of Leigh syndrome.

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