Autosomal Recessive Spastic Ataxia of Charlevoix-Saguenay due to Novel Mutations in the SACS Gene.

Autosomal recessive spastic ataxia of Charlevoix-Saguenay (ARSACS) is characterized by triad of progressive cerebellar ataxia, progressive spasticity, and axonal/demyelinating peripheral neuropathy. Other manifestations include dysarthria, weakness in lower extremities and distal muscle wasting, foot deformities, retinal striation, prolapse of the mitral valve and rarely intellectual disability, hearing loss, and myoclonic epilepsy. We describe a patient who developed peripheral sensorimotor neuropathy in the absence of spasticity on initial presentation. He had nerve root enhancement on magnetic resonance imaging (MRI) lumbar spine, and nerve conduction studies were suggestive of demyelinating polyneuropathy. Patient had mild cerebellar atrophy on MRI and some delay of motor milestones. Over the course of several months, he developed spasticity, and genetic analysis together with clinical presentation was consistent with ARSACS. He was noted to have a pathogenic mutation c.8108G>A (p. Arg2703His) inherited from mother and a variant of uncertain significance c.7216T>C (p. Ser2406Pro) inherited from his father in SACS gene. Atypical cases may present later in life or in absence of one of the classical features at the time of presentation, which may make diagnosis difficult. Our patient had such an atypical presentation of ARSACS. Young patients with neuropathy and concomitant cerebellar atrophy on MRI should raise suspicion for hereditary spastic ataxia syndrome. Follow-up examination can often reveal additional findings to aid the diagnosis.

Limb-Girdle Muscular Dystrophy R9 due to a Novel Complex Insertion/Duplication Variant in FKRP Gene.

Limb-girdle muscular dystrophy R9 (LGMD2I, LGMDR9) is an autosomal recessive disorder caused by pathogenic variants in the fukutin-related protein (FKRP) gene. We describe a 17 year old boy with LGMDR9 whose symptoms began at age 5 years. Muscle histopathology, immunostaining, and western blotting were consistent with a dystroglycanopathy. Genetic testing identified maternal inheritance of the most common pathogenic FKRP variant c.826C>A (p.L276I). Also detected was a novel insertion and duplication on the paternally inherited FKRP allele: a single nucleotide insertion (c.948_949insC) and an eighteen nucleotide duplication (c.999_1017dup18) predicted to result in premature translation termination (p.E389*). Based on the clinical features and course of the patient, heterozygosity for the common pathogenic FKRP variant, and abnormal glycosylation of alpha-dystroglycan, we suggest that the novel FKRP insertion and duplication are pathogenic. This case expands the genetic heterogeneity of LGMDR9 and emphasize the importance of muscle biopsy for precise diagnosis.

Use of Head Computed Tomography (CT) in the Pediatric Emergency Department in Evaluation of Children With New-Onset Afebrile Seizure.

OBJECTIVE: Cranial computed tomography (CT) is not recommended in the routine evaluation of children with first afebrile seizure due to its low yield. The objective was to assess the current practice in our pediatric emergency department regarding the use of head CT in children with first afebrile seizure and to identify the factors that lead to ordering a head CT. METHODS: Medical records of patients between 1 month and 18 years old evaluated at our emergency department for presentation of first afebrile seizure between 2010 and 2014 were retrospectively reviewed. Data extracted include age, gender, seizure type, single or multiple seizures at presentation, seizure duration, predisposing conditions to seizures (ie, history of developmental delay), and whether a head CT was performed. Contingency tables with chi-square analyses were used to determine which variables were associated with increased use of head CT. RESULTS: Of 155 patients (88M/67F) included in the study, 72 (46.5%) underwent head CT and only 3 had clinically significant findings that did not require acute management. There were no differences in CT use by age, sex, seizure type, seizure number, seizure risk factors, or findings on physical examination. Head CT was performed more frequently in cases with seizures ≥5 minutes and unknown seizure duration ( P = .04). CONCLUSION: Despite existing evidence, the emergent head CT rate was high in our cohort. Children with seizure duration of ≥5 minutes or of unknown duration were more likely to undergo head CT in our emergency department.

Early-onset epileptic encephalopathy with myoclonic seizures related to 9q33.3-q34.11 deletion involving STXBP1 and SPTAN1 genes.

We describe a 10-month-old boy with early-onset epileptic encephalopathy who was found to have a hemizygous deletion in 9q33.3-q34.11 involving STXBP1 and SPTAN1 genes. He presented at the age of 2.5 months with frequent upper extremity myoclonus, hypotonia, and facial dysmorphisms. Interictal EEG showed multifocal polyspike and wave during wakefulness and sleep. Ictal EEG revealed low-amplitude generalized sharp slow activity, followed by diffuse attenuation. Metabolic testing was unrevealing. Brain MRI showed thinning of the corpus callosum with an absence of rostrum. This patient is the second reported case with 9q33.3-q34.11 deletion involving STXBP1 and SPTAN1 genes associated with epileptic encephalopathy and myoclonic seizures. Larger case series are needed to better delineate this association.