Does treatment with methylphenidate correlate with tremor severity for patient with possibly genetic dystonia: case report

Abstract

Objectives Dystonia is a movement disorder characterized by sustained or intermittent muscle contractions causing abnormal, often repetitive movements and/or postures. Dystonic movements are typically patterned and twisting, and may be associated with tremor. Dystonia is often initiated or worsened by voluntary action and associated with overflow muscle activation. Most forms of dystonia tend to worsen initially. There are various types of dystonia and one of isoleted dystonia type caused by ANO3 gene variants. Materials and Methods We report a teenage patient case with progressive tremor and dysarthria treated with methylphenidate. Results Our patient is a 17-year-old female, the main complaints being progressive hand and head shaking. The tremor is more prominent after physical and emotional exertion. Progressive dysarthria was also observed during the recent years, starting from 10 years of age. The patient’s mother had intellectual disability and died while giving birth to the patient’s sister. The patient has 4 sisters with developmental problems and/or intellectual disability. No tremors or other movement disorders have been documented in the family. The patient lives in a social community home and is under the supervision of a child and adolescent psychiatrist due to her intellectual disability, schooling difficulties, attention-deficit/hyperactivity disorder (ADHD) and hair self-picking from 10 years of age. She has also been diagnosed with ulcerative colitis and is taking mesalasine for the treatment. Hand tremor has been progressing during follow-up time: the patient experiences difficulties in writing or handling a fork and a spoon, she also drops and spills out food while eating. The girl’s intellectual abilities (IQ) were assessed with Wechsler Intelligence Scale for Children–III (WISC-III) twice in 5-year period: verbal IQ showed increasing scores (70 --> 82), and nonverbal IQ showed regression (80 --> 73), total IQ remaining quite stable (72 --> 76). Neurological examination showed unvoluntary tongue movements, hyperreflexia in lower limbs and mild tremor in hands. Muscle tone was found to be normal so far. No structural Whole exome sequencing (WES) was performed and heterozygous variant of unknown significance NM_031418.4(ANO3):c.[1943A>G];[1943=], p.Asn648Ser was found. Unfortunately, it was not possible to do segregation analysis. The patient was prescribed methylphenidate XL 18 mg/d for ADHD, and improvement of tremor was noticed. Unfortunately, due to elongated QTc interval on ECG, now methylphenidate treatment is contraindicated for this patient. Conclusions The detected variant of ANO3 gene may be the cause the patient’s dystonia phenotype. Further follow-up of the patient is planned. We hypothesize that methylphenidate possibly improved dystonia symptoms, but more studies are needed. We are also seeking for other treating modalities to control the symptoms.