Very Early-Onset Schizophrenia in a Six-Year-Old Boy
Publication: American Journal of Psychiatry Residents' Journal
Very early-onset schizophrenia is characterized by hallucinations, delusions, and cognitive impairment in children less than 13 years old. The prevalence of very early-onset schizophrenia is unknown but is estimated to be 1:30,000 children. Very early-onset schizophrenia is the pediatric counterpart to early-onset schizophrenia, which affects adolescents 13–18 years old, and adult-onset schizophrenia, which affects individuals over 18 years old (1). Although the DSM does not differentiate between very early-onset schizophrenia, early-onset schizophrenia, and adult-onset schizophrenia, the age at onset of schizophrenia can have distinct clinical ramifications. Very early-onset schizophrenia tends to present insidiously, with a premorbid period characterized by developmental delay and diminished school performance. Oftentimes, children with very early-onset schizophrenia are misdiagnosed with pervasive developmental disorder before they develop florid psychosis (2). As very early-onset schizophrenia progresses, it shares more clinical features with early-onset schizophrenia and adult-onset schizophrenia, including hallucinations, delusions, and paranoia. However, it tends to be more severe and disabling than adult-onset schizophrenia, resulting in lower educational performance and poorer social relationships (1). It is also characterized by a higher rate of cytogenetic abnormalities than adult-onset schizophrenia (3), suggesting that affected individuals carry an even stronger genetic predisposition to schizophrenia. We describe the case of a 6-year-old boy with new-onset schizophrenia, who showed unusual behavior suggestive of psychotic symptoms as early as infancy.
Case
“Kyle” is a 6-year-old boy with a history of mild developmental delay who presented with one month of disorganized behavior, hallucinations, and developmental regression. At 3 months old, he began tracking objects his parents were unable to see. At 7 months old, he began visually fixating on unseen objects and would “open his eyes widely, become very excited, flap his arms, and tense his legs,” according to his mother. He did not begin walking until 20 months old and was referred to early intervention for gross motor delay. At age 3, he began talking to someone his parents could not see, leading them to believe he had an imaginary friend. While learning to read at age 5, he would say, “Stop mom! The words are talking back!” This possibly suggests an experience of auditory hallucinations. In kindergarten, he was held back due to poor attention but remained socially interactive without grossly abnormal behavior. Then, one month prior to admission, he developed frank hallucinations and severe social withdrawal. He frequently whispered to himself nonsensically and was so internally preoccupied that he often was unable to follow commands. The patient's family history was notable for 1) schizophrenia in a maternal cousin, two paternal cousins, and his paternal great grandmother; 2) bipolar disorder in two paternal cousins; and 3) autism in a paternal cousin and a paternal great aunt. His pediatrician performed a preliminary workup, including routine laboratory examination and a CT of the head, which were normal. The pediatrician referred the patient for admission to our hospital.
On initial evaluation, the child appeared thin and younger than his stated age. His mother stated that he had been eating only intermittently, resulting in significant weight loss and failure to thrive (body mass index=14.5, weight <10th percentile; height <3rd percentile). His behavior was notable for stereotyped pursing of his lips, repetitive blinking, and poor eye contact. The child was mumbling to himself, and upon questioning, his speech was impoverished and disorganized. His affect was flat and intermittently guarded. He endorsed visual hallucinations of “people in [his] eyes” who were “following [him] everywhere,” named “Shavonni, James, and Jack,” who appeared “black with yellow teeth and green eyes.” The child's mother endorsed that he had a history of paranoid delusions that people were chasing him or taking away his food. He expressed passive suicidal ideation, saying, “God said it's time for me to come to heaven,” as well as homicidal ideation toward an unclear target, saying “I'm gonna cut you up; I'm gonna kill you.” He did not exhibit self-injurious or violent behavior.
The patient received a comprehensive medical workup, including MRI of the brain, lumbar puncture (with oligoclonal bands, myelin basic protein, paraneoplastic, and N-methyl-D-aspartate receptor antibody testing), EEG, rheumatologic screening (with antinuclear antibody, C-reactive protein, erythrocyte sedimentation rate, ceruloplasmin, celiac, and thyroid testing), metabolic screening (with lactate, pyruvate, acylcarnitine, urine organic acid, and plasma amino acid testing), urine drug screen, and heavy metal panel, which were normal. The consulting psychiatrist deferred initiation of antipsychotic medications given the patient's age and instead started clonazepam for agitation control. Given the patient's unusually young age at presentation, possible lifelong symptoms, and a strong family history of mental illness, he was referred for genetic testing. Chromosome single nucleotide polymorphism microarray analysis showed a 22q11.2 deletion (low copy repeat-A/low copy repeat-D).
Discussion
22q11.2 deletion syndrome is the most common chromosomal microdeletion syndrome. The 22q11.2 region contains large areas of low copy repeats, which are subject to meiotic error, resulting in recombination and subsequently deletions, most commonly between low copy repeat-A and low copy repeat-D. The syndrome encompasses a wide spectrum of manifestations, including congenital heart defects; chronic infections; palatal, parathyroid, and gastrointestinal abnormalities; and behavioral differences. Oftentimes, children with 22q11.2 deletion syndrome have speech delay, with their first words at 24 months (4). Perhaps most concerning, 75% of individuals with 22q11.2 deletion syndrome are affected by psychiatric illness, most commonly autism, attention deficit hyperactivity disorder, anxiety, and psychosis. Specifically, patients with 22q11.2 deletion syndrome are at a 25-fold increased risk for developing a psychotic disorder compared with the general population, and nearly 25% of these patients develop schizophrenia (5).
Twin, family, and adoption studies have shown that hereditary factors have a strong influence on the development of schizophrenia (6). However, only several genomic regions have been linked to schizophrenia, and there have been no individual causative genes identified. The 22q11.2 microdeletions are the only confirmed copy number variation known to cause schizophrenia (7). The genetics of schizophrenia appear to be highly complex, with numerous genes of minor effect interacting with each other to produce the phenotype. Attention has most recently turned to the role of epigenetics in the development of disease (6). It has been hypothesized that the genes responsible for the development of schizophrenia might be abnormal transcriptional units that code for RNA regulators of protein coding gene expression, rather than abnormalities in the coding genome itself (8).
The above case not only underscores the heritability of schizophrenia, but also is noteworthy for the clinical signs that preceded the patient's first break psychotic episode. Delayed milestones in all domains, including motor, speech, social, and cognitive development, characterize the premorbid period of schizophrenia. This effect is more pronounced in those with very early-onset schizophrenia than in those with early-onset or adult-onset schizophrenia (9). Stereotyped behaviors, such as flapping and echolalia, are also frequently present and can lead to a misdiagnosis of pervasive developmental disorder (2). Additionally, the premorbid period of very early-onset schizophrenia is often punctuated by declining academic function, with accelerating deterioration when the acute psychotic phase approaches. In the above case, the patient presented with nearly all of these predictive clinical signs, including developmental delay, stereotypy, and a decline in academic performance necessitating withdrawal from kindergarten.
Many clinicians are hesitant to make a diagnosis of very-early onset schizophrenia, with an average of 2 years from onset of symptoms to diagnosis. One challenge to diagnosis lies in the decision to attribute hallucinations to a pathological process given that non-pathological hallucinations occur in 8% of children. Contextual information is essential in making these distinctions, with special attention to the preservation of social relationships, higher premorbid functioning, and environment-specific symptoms (2, 9). Once a diagnosis is made, considerable controversy exists surrounding the use of antipsychotics in children due to limited data on safety and efficacy. Antipsychotics are generally recommended for severe cases, with evidence to suggest that early initiation improves outcomes, especially control of positive symptoms. The present case highlights that subtle clinical signs, including developmental delay, stereotypy, academic decline, and possible hallucinations, can herald the development of very early-onset schizophrenia.
Key Points/Clinical Pearls
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Very early-onset schizophrenia is defined as the onset of schizophrenia in children less than 13 years of age; DSM criteria for diagnosis are the same as adult-onset schizophrenia.
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Very early-onset schizophrenia has a premorbid period characterized by global delay in domains of motor, speech, social, and cognitive development; it is often misdiagnosed as pervasive developmental disorder due to the presence of stereotypy.
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The genetics of schizophrenia are largely unknown; the 22q11.2 microdeletion is the only copy number variation associated with schizophrenia.
Acknowledgments
The authors thank Dr. Avram Mack for his mentorship of Dr. Roth and assistance with conceptualization of this article. The authors also thank Dr. Elaine Zackai for her mentorship of Dr. Matalon and her endlessly inspiring clinical acumen that led to the patient's diagnosis, as well as Donna McDonald-McGinn, M.S., CBC, for her groundbreaking work on the neuropsychological manifestations of 22q11 deletion syndrome.
References
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Squarcione C, Torti MC, Fabio FD, et al: 22q11 deletion syndrome: a review of the neuropsychiatric features and their neurobiological basis. Neuropsychiatr Dis Treat 2013; 9:1873–1884
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American Journal of Psychiatry Residents' Journal
Pages: 9 - 11
History
Published in print: February 01, 2017
Published online: 10 February 2017
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