[source]
pmid = PMID:28966590
title = TUBB2B Mutation in an Adult Patient with Myoclonus-Dystonia
[diagnosis]
disease_id = OMIM:610031
disease_label = Cortical dysplasia, complex, with other brain malformations 7
[text]
A 31-year-old, right-handed, Caucasian woman of Northern European ancestry presented to the Neurogenetics Clinic at the
National Institutes of Health (Bethesda, MD, USA) for evaluation of myoclonus-dystonia. Her parents were neurologically healthy;
however, her sister had died at age 30 years of genetically confirmed Friedreich ataxia. The patient herself did not
carry a pathologic FXN expansion. She was born at full-term via an uncomplicated vaginal delivery after an uneventful pregnancy,
weighing 3.35 kg. Her Apgar scores at 1 and 5 minutes were 8 and 9. She had minor motor delays throughout infancy,
such as not crawling until 10 months and a tremor with minimal head tilt by 12 months. At this time, she was diagnosed with mild cerebral palsy.
At 24 months, she began walking and speaking, but required physical therapy for balance problems.

Cervical dystonia became apparent at age 16 years, presenting with involuntary left head tilt and left torticollis.
Subsequently, she developed intermittent upper body myoclonus, confirmed to be nonepileptic in nature by EEG.
Her movement disorder has been static since that time, and has been treated symptomatically with trihexyphenidyl.
Carbidopa/levodopa had been briefly tried without any symptomatic improvement.
She was taking Ritalin for attention deficit disorder for many years. She graduated from a high school that emphasized
special education and attended 1 year of community college. She has been working full-time as a receptionist.
At age 30 years, she had her first generalized, tonic-clonic seizure.
She was started on 750 mg of levetiracetam 2 times daily for seizure prophylaxis, and remains seizure free.
During the most recent neurological exam (age 31 years), the patient displayed mild cognitive impairment (Montreal Cognitive Assessment Test Score: 22/30).
Her speech was fluent and grammatically correct. Her occipital frontal circumference was 57 cm (approximately 1 standard deviation
above the mean for her gender and height). Her gaze was slightly dysconjugate, though her extraocular movements were otherwise intact.
She had a slight left laterocollis and mild left torticollis with hypertrophic right sternocleidomastoid and trapezius muscles.
Occasional myoclonic jerks were apparent in her neck, trunk, and upper extremities. She had a low amplitude, high frequency postural tremor in her left hand.
Muscle tone and bulk were normal throughout. Reflexes were 2+ and symmetric. Babinski reflex was negative bilaterally.
Musculoskeletal examination demonstrated bilateral genu valgum deformity, left hip dysplasia, and dextroscoliosis with lumbar hyperlordosis.

Skin biopsy showed no evidence of a storage disorder, and all blood panels were within normal limits (complete blood count, complete metabolic panel,
amino acids, thyroid stimulating hormone, free thyroxine 4, ceruloplasmin, heavy metals, organic acids, and triglycerides).
Brain MRI revealed numerous structural abnormalities, suggestive of a neuronal migrational disorder (Fig.1).
Isolated lissencephaly was noted with asymmetric temporal and parietal pachygyria. Enlarged and dysmorphic lateral ventricles, dysmorphic basal ganglia,
dysmorphic hippocampi, and mild superior vermian cerebellar dysplasia were also present. Her corpus callosum and cerebellar hemispheres appeared structurally normal
MR images illustrate pachygyria in horizontal (a) and coronal (b) sections in the brain of the patient.
a Irregular cortical surface with asymmetrically enlarged gyri is indicated by white arrows; the lateral ventricles are enlarged and dysmorphic
in appearance with dysmorphic basal ganglia (white stars). The hippocampi appear dysmorphic and asymmetrical (white triangles in b), while the
superior cerebellar vermis is mildly dysplastic (white circle in a).