Comorbid Bipolar Disorder and Usher Syndrome

Abstract

To the Editor: Co-occurrence of psychiatric disorder and rare syndromes with known gene loci can facilitate critical pathophysiologic insights and might have important therapeutic implications as well.1 Usher syndrome is the most common type of deaf-blindness. It is a group of genetically distinct disorders phenotypically associated with dual sensory impairments as a result of congenital sensorineural hearing loss and progressive visual impairment from retinitis pigmentosa. Rarely, Usher syndrome may be associated with mental subnormality and infertility. Twenty-three percent of these patients have a psychiatric illness, mainly schizophrenia.1,2 Pathogenic Usher protein complex is a group of proteins that are neurosensory receptors at the outer hair cells of the inner ear and the retinal photoreceptor cells and are encoded by different genes present on the chromosomes 1, 8, and 14.3,4 Mutation of any one of the multiple genes in these chromosomes leads to the symptom complex of Usher syndrome. Although co-occurrence of psychosis with Usher syndrome has been reported,5–7 co-occurrence of bipolar disorder has not been reported. For the first time, we report a patient with bipolar disorder and Usher syndrome and the treatment implications. Case report. Mr A, a 25-year-old man, presented to our hospital in December 2007 with a history of elated mood, overactivity, overtalkativeness, overfamiliarity, delusions of grandiosity, decreased need for sleep, and decreased appetite for the past 3 months. In the past, Mr A had experienced 2 episodes of mania that responded to treatment with haloperidol, with complete remission of symptoms. He also had a history of congenital hearing impairment and night blindness. There was a family history suggestive of congenital deafness and night blindness in a first-degree relative. Results of investigations, namely, hemogram, liver function tests, kidney function tests, and serum electrolytes, were normal. Magnetic resonance imaging did not reveal structural abnormalities. He was evaluated using the Mini International Neuropsychiatric Inventory8 and diagnosed as having bipolar affective disorder with psychotic symptoms (ICD-10). He had a score of 16 on the Young Mania Rating Scale (YMRS).9 Audiometry showed sensorineural hearing loss for 4–8 kHz, and ophthalmic examination revealed retinitis pigmentosa, suggestive of Usher syndrome. Mr A was started on treatment with lithium 600 mg/d for management of bipolar disorder. Subsequently, he developed hyperpigmented papular and pustular lesions involving the skin and buccal mucosa. Dermatologic opinion was sought, resulting in a diagnosis of pemphigus vulgaris, and treatment with prednisolone 30 mg/d was advised. In view of this, lithium treatment was stopped and treatment with risperidone 4 mg/d and valproate 1000 mg/d was started. He improved with this medication and at the end of 2 weeks had a score of 4 on the YMRS. Mr A had no new skin lesion, and he maintained euthymia at the end of 1 year. To the best of our knowledge, this is the first report of the co-occurrence of Usher syndrome and bipolar disorder. Our patient had high-frequency sensory neural hearing loss and atypical retinitis pigmentosa suggestive of Usher syndrome. He developed significant side effects when lithium treatment was started. One should be cautious of dermatologic side effects when starting lithium treatment in patients with comorbid Usher syndrome. This report exemplifies the need for systematic assessment of patients with bipolar disorder in liaison with other specialties for comorbid conditions whenever indicated. Interestingly, chromosomes 8 and 14 are also implicated in linkage studies of bipolar disorder.10 Further molecular biologic studies of such patients with comorbid bipolar disorder might facilitate better understanding of the pathogenesis of bipolar disorder.