A 7-year-old girl presents with a progressive dystonia affecting her left leg, which makes her gait abnormal. Her symptoms are noted to be worse in the afternoon and evening and improve after a night’s sleep. A diagnosis of dopa-responsive dystonia (Segawa syndrome) is suspected. A pathogenic variant in which of the following genes is the most common cause of this autosomal dominant disorder?
A term infant born after an uncomplicated pregnancy and delivery presents at 9 months with delayed motor milestones and is later diagnosed with spastic quadriplegia. An MRI of the brain does not show evidence of hypoxic-ischemic injury or stroke. What is the most likely underlying etiology for this child’s cerebral palsy?
A 6-year-old boy with a known diagnosis of Tuberous Sclerosis Complex undergoes routine surveillance imaging. A brain MRI shows a new, growing but asymptomatic subependymal giant cell astrocytoma (SEGA). What is the most appropriate next step in management?
A 1-year-old child presents with developmental regression, intractable epilepsy, and an MRI of the brain showing findings consistent with Leigh syndrome. Subsequent genetic testing reveals a pathogenic variant in the POLG gene, confirming a diagnosis of Alpers-Huttenlocher syndrome. Which of the following medications is absolutely contraindicated in this child?
A 5-year-old boy presents with refractory status epilepticus. His brain MRI reveals extensive, multifocal hyperintense cortical-subcortical FLAIR/T2 abnormalities. He has no significant psychiatric symptoms or prominent dyskinesias. Cerebrospinal fluid analysis is positive for neuronal antibodies. Which type of autoimmune encephalitis is most likely in this patient?
A 14-year-old girl is diagnosed with a mitochondrial disorder after presenting with progressive myoclonic epilepsy and cerebellar ataxia. A muscle biopsy shows ragged red fibers. This clinical syndrome is known as Myoclonic Epilepsy with Ragged Red Fibers (MERRF). What is the most common underlying genetic variant for this condition?
A 9-year-old girl presents with a 3-week history of involuntary, dance-like movements of her limbs and emotional lability following a sore throat. What is the primary pathophysiologic mechanism believed to cause the neurologic manifestations of this disorder?
An 8-year-old child presents with vertical diplopia that is most noticeable when walking down stairs. On examination, you observe that the child maintains a compensatory head tilt away from the affected side to alleviate the double vision. Paralysis of which cranial nerve is the most likely cause of these specific findings?
A 9-year-old boy is evaluated for a 2-year history of progressive clumsiness. On examination, he has marked ataxia of his lower extremities, an explosive, dysarthric speech, absent deep tendon reflexes at the ankles, and high-arched feet. Which genetic mechanism is most likely responsible for his condition?
A 5-month-old male presents with infantile spasms and severe developmental delay. A brain magnetic resonance imaging scan shows lissencephaly. His 19-year-old sister has a history of seizures that began in adolescence and is found on imaging to have subcortical band heterotopia (“double cortex”). A pathogenic variant in which of the following genes best explains the differing phenotypes in this family?
