Usher syndrome with psychotic symptoms: Two cases in the same family


Chih-Chiang Chiu, MD, Department of Psychiatry, Taipei City Psychiatric Center, ♯309, Songde Road, Taipei, Taiwan. Email:


Abstract  Usher syndrome is a heterogeneous autosomal recessive disorder characterized by hearing and visual sensory impairment. Retinitis pigmentosa is essential for its diagnosis. There are only a few reports describing patients with Usher syndrome presenting with psychotic features and the etiology of its psychiatric manifestation is still unknown. Herein, the authors report variable congenital hearing impairment and progressive visual loss occurring in five of seven family members and two of them meeting the diagnostic criteria of Usher syndrome with psychotic features. Furthermore, the authors compare their psychiatric symptoms with other reports and the possible etiologies of psychotic symptoms are discussed.


Usher syndrome is a heterogeneous autosomal recessive disorder characterized by dual sensory impairment, that is, profound congenital hearing impairment and progressive visual loss due to retinal degeneration. Retinitis pigmentosa is essential for the diagnosis of Usher syndrome.1 Two types established by Charles Usher are forms which can be divided clinically.1 Patients with Usher syndrome type I have severe congenital hearing impairment, vestibular dysfunction, and retinal degeneration since the first decade. Others with type II have moderate hearing impairment, preserved vestibular function, and relative late onset retinitis pigmentosa. Gene mutations in several locations (1q, 3q, 5q, 10q, 11q, 21q etc.) associated with Usher syndrome2 have been reported. However, most genetic researches emphasize sensory impairment. There are only a limited number of reports with descriptions about the psychotic features of Usher syndrome, in which queer behaviors, irritability, anxiety, depression, Capgras syndrome, schizophrenia-like symptoms, function deterioration course, and withdrawing from work have been found.3–5 Even though these patients are deaf, auditory hallucinations are suspected. Nevertheless, the etiology of its psychiatric manifestation is still unknown and rarely discussed by professionals. Until now, only one report, which found central nervous system changes in a case of Usher’s syndrome with schizophrenia-like mental disorder, was Asian people.6 Herein, the authors report that variable congenital hearing impairment and progressive visual loss occur in five of seven family members and two of them meet the diagnostic criteria of Usher syndrome and present with psychotic symptoms.


A 35-year-old female with her highest education level being elementary school, suffered from congenital hearing impairment and progressive loss of vision to light sensation. She used hearing aids and communicated with other people using few words and body language. She worked in a factory for 3 years after elementary school, and stopped working due to visual impairment at about 16 years old. Retinitis pigmentosa was confirmed by the ophthalmologist. Her general function had deteriorated and disturbance behavior gradually increased since 24 years of age. Frequent self-talking and shouting into the air like arguing and fighting with someone else were combined. Nevertheless, she was still oriented and was able to care for herself in daily life well. She was brought to visit psychiatrists at the age of 24 and hospitalized once for her aggressive behaviors towards her grandmother. Symptoms of suspected visual and auditory hallucinations, irritability and function deterioration were noted without negative symptoms. After consulting a neurologist, no abnormal finding of neurological exam was revealed. In addition, no specific abnormal result was revealed throughout the authors’ routine tests during admission, such as blood biochemistry, urine and stool examination, chest X-ray, and electrocardiogram. However, her brain computed tomography (CT) showed general mild brain atrophy, and electroencephalogram revealed non-specific findings of diffuse mild slow waves. Although a standard intelligence quotient test could not be conducted, borderline to lower intelligence rather than moderate to severe mental retardation was suspected according to her simple occupational ability and limitations of performing complicated tasks before psychotic symptoms flared-up. Thereafter, haloperidol 15 mg and valproic acid 1000 mg were prescribed but irregularly administered by her after being discharged from hospital. Although self-talking was noted intermittently, the irritability and aggressive behavior decreased. Furthermore, she suffered from a function deterioration course which working, simple tasks, and meaningful communication that would be easy for her at the age of 24 now became impossible.


Her 32-year-old brother suffered from congenital nearly complete deafness, delayed speech, and gradual visual loss to only light sensation since 15 years old. He graduated from a special high school, performing strongly. He communicated with others using sign language, a few words, and by writing, although some words he said or wrote were difficult to recognize. However, disturbing and destructive behaviors developed gradually at about 17 years old. Similar features to his sister were noted, such as self-talking to an empty chair and writing to workers that someone would poison or do harm to him, so that auditory hallucination and persecutory delusion were suspected, but no definite negative symptom was found. There were no abnormal findings in his routine tests and neurological tests during admission. Also, his brain electrography was within the normal range. However, he and his family refused to allow further brain CT examination. It was also difficult to evaluate his intelligence. Borderline to lower intelligence was suspected because of his preserved function of daily life, meaningful communication with writing and sign language, and good performance at special school. Haloperidol 20 mg improved his disturbing behaviors, but had a limited effect on self-talking. Delusion of persecutory persisted, but did not affect his daily life. There was no definite function deterioration noted.


Although there was neither alcohol dependence nor any other substance abuse history in these two cases, their father had the problem of alcohol dependence instead of sensory impairment and died from liver disease several years earlier. Both their mother and the eldest brother had one-eye-blindness without hearing impairment and with suspected borderline to lower intelligence. The other elder brother had night blindness and had graduated from college. The youngest sister was the only sibling without sensory impairment and she had a normal range of intelligence. No other psychiatric disorders, including schizophrenia and substance abuse, nor medical disease histories, were found in this family (Fig. 1).

Figure 1.

The family tree for these two cases with Usher syndrome. Gray color – Two patients with Usher syndrome. Gray color in half – The mother and the eldest brother have one-eye-blindness but without hearing impairment. Slashed shadowed in half – The other elder brother has night blindness and graduated from college. Dotted shadowed in half – The father had alcohol dependence. There is no detailed information about their grandparents.

Based on teenage onset of retinitis pigmentosa, no profound hearing impairment, and family history, these two cases presented here fit with the diagnostic criteria of Usher syndrome type II. According to previous case reports,3–6 the most common presented psychiatric symptoms in patients with Usher syndrome are disturbing behaviors and suspected auditory hallucinations. There are two cases3–6 suspected of type II Usher syndrome according to their latter onset courses and one diagnosed as type I in childhood. There is no significant consistency in type and psychotic symptoms in these cases. Otherwise, the two present cases’ symptoms of disturbing behaviors and auditory hallucinations are similar to previous reports.

The etiology of the psychotic symptoms in Usher syndrome remains unclear. Usher syndrome is clinically and genetically heterogeneous, although two clinical types have been described. Moreover, studies of relationship between genotype and phenotype are still going on. Two genetic loci associated to Usher syndrome, 11q in type I and 5q in type II, are also reported in schizophrenia and, therefore, imply a relationship between these two diseases.6 Further genetic studies to explore the possibility linkage are warranted. Interestingly, the psychotic symptoms of these two cases developed at a similar age to that of patients with schizophrenia.

In addition, the influence of sensory deprivation itself in these patients should be taken into consideration when we discuss the etiology of their psychotic symptoms. In this family, only these two members that meet the full criteria for Usher syndrome have psychotic symptoms. Whether or not the presence of psychotic symptoms might be related to more severe sensory deprivation should be studied. Furthermore, the organic deficit may be another possible causing factor. Significant decrease in intracranial volume and in size of the brain and cerebellum with a trend toward an increase in the size of the subarachnoid spaces are found in patients with Usher syndrome, which reveals that the disease process involved the entire brain and is not limited to the posterior fossa or auditory and visual systems.7 Those also suggest that the psychosis of Usher syndrome might be secondary to a general degeneration involving whole brain more diffusely.

According to the hypothesis described above, it is still difficult to truly understand the etiology of the present cases. However, there is a variety of sensory impairment and intelligence problems in other family members. The psychotic symptoms of these two cases are followed by their sensory deprivation. Also, brain atrophy is noted in the CT scan of this sister. Taken together, the possible etiology of these two cases presenting with psychotic symptoms in the Usher syndrome may be due to the intertwining of three possible effects: inheritance, sensory deprivation, and organic deficit of brain.

Making diagnosis of people with dual sensory impairment should be conducted carefully due to their limited communication. Changes of behaviors, contents of communication, and deterioration of their function are important clues to suspect the existence of psychotic symptoms. Accordingly, the prevalence rate of Usher syndrome may range from 2 to 6.2 per 100 0008,9 and nearly 23.3%9 patients are psychotic. Although there is no data which reveals the prevalence rate of Usher syndrome among Asian people, more attention should be paid to evaluating the mental status of patients with variable sensory impairment, such as Usher syndrome, due to its high prevalence rate of psychosis and difficulty in being diagnosed.