Posts tagged 22q11.2 deletion syndrome

UC Davis MIND Institute research finds rigorous evaluations are needed to accurately diagnose autism in children with 22q11.2 deletion syndrome

Children with a genetic disorder called 22q11.2 deletion syndrome, who frequently are believed to also have autism, often may be misidentified because the social impairments associated with their developmental delay may mimic the features of autism, a study by researchers with the UC Davis MIND Institute suggests.

The study is the first to examine autism in children with chromosome 22q11.2 deletion syndrome, in whom the prevalence of autism has been reported at between 20 and 50 percent, using rigorous gold-standard diagnostic criteria. The research found that none of the children with 22q11.2 deletion syndrome “met strict diagnostic criteria” for autism.

The researchers said the finding is important because treatments designed for children with autism, such as widely used discrete-trial training methods, may exacerbate the anxiety that is commonplace among the population.

Rather, evaluations should be performed to assess autism and guide the selection of appropriate therapies based on the children’s symptoms, such as language and communication delay, the researchers said. The study, “Social impairments in Chromosome 22q11.2 Deletion Syndrome (22q11.2DS): Autism Spectrum Disorder or a different Endophenotype?” is published online today in Springer’s Journal of Autism and Developmental Disorders.

A high prevalence of autism spectrum disorder has been reported in children with 22q11.2 deletion syndrome – as high as 50 percent based on parent-report measures. Children diagnosed with 22q11.2 deletion syndrome – or 22q – may experience mild to severe cardiac anomalies, weakened immune systems and malformations of the head and neck and the roof of the mouth, or palate. They also experience developmental delay, with IQs in the borderline-to-low-average range. They characteristically experience significant anxiety and appear socially awkward.

“The results of our study show that of the children involved in our study no child actually met strict diagnostic criteria for an autism spectrum disorder,” said Kathleen Angkustsiri, study lead author and assistant professor of developmental-behavioral pediatrics at the MIND Institute.

“This is very important because the literature cites rates of anywhere from 20 to 50 percent of children with the disorder also have an autism spectrum disorder. Our findings lead us to question whether this is the correct label for these children who clearly have social impairments. We need to find out what interventions are most appropriate for their difficulties.”

The disorder’s name also describes its location on the 22^nd chromosome as well as the nature of the genetic mutation, which is associated with a variety of anatomical and intellectual deficits.  It has previously been known as Velocardiofacial Syndrome and Di George Syndrome, for the pediatric endocrinologist who described it in the 1960s.

The risk of 22q is about 1 in 2000 in the general population. The condition is seen in individuals of all backgrounds. Notably, people with 22q are at significantly heightened risk of developing mental-health disorders in adolescence and young adulthood. A person with 22q has a 30 times greater risk of developing schizophrenia than individuals in the general population.

“Because of the high rates of psychiatric disorders in childhood and adulthood, 22q is a very special population for prospective study looking at what’s happening throughout childhood that might either increase risk or provide protection against some of the later developing serious psychiatric illnesses, such as schizophrenia, that are associated with the disorder,” said Tony J. Simon, professor of psychiatry and behavioral sciences and director of the chromosome 22q11.2 deletion program at the MIND Institute.

The study was conducted among individuals recruited through the website of the Cognitive Analysis and Brain Imaging Laboratory (CABIL), which Simon directs. Simon and Angkustsiri said that the parents of children with 22q deletion syndrome often had commented that their children “seemed different” from other children with autism diagnoses, but that they hadn’t discovered a better diagnosis.

The clinical impression of the MIND Institute’s 22q deletion syndrome team, which includes psychologists Ingrid Leckliter and Janice Enriquez, was that the children were experiencing significant social impairments, but their presentation diverged from that of children with autism. To determine whether the children met the criteria for classic autism, they decided to test a subset of the children recruited from participants in a larger study of neurocognitive functioning, based on stringent methods and using multiple testing instruments.

The researchers selected 29 children –16 boys and 13 girls – for additional scrutiny, administering two tests. The Autism Diagnostic Observation Schedule (ADOS), a gold-standard assessment for autism, was administered to the children. The Social Communication Questionnaire (SCQ), a 40-question parent screening tool for communication and social functioning based on the gold-standard Autism Diagnostic Interview-Revised, was administered to their parents.

Typically, a diagnosis of autism spectrum disorder requires elevated scores on both a parent report measure, such as the SCQ, and a directly administered assessment such as the ADOS.  Prior studies of autism in chromosome 22q11.2 deletion syndrome have only used parent report measures.

Only five of the 29 children had scores in the elevated range on the ADOS diagnostic tool. Four of the five had significant anxiety. Only two – 7 percent – had SCQ scores above the cut off. No child had both SCQ and ADOS scores in the relevant ranges that would lead to an ASD diagnosis.

 “Over the years, a number of children came to us as part of the research or the clinical assessments that we perform, and their parents told us that they had an autism spectrum diagnosis. It’s quite clear that children with the disorder do have social impairments,” Simon said. “But it did seem to us that they did not have a classic case of autism spectrum disorder. They often have very high levels of social motivation. They get a lot of pleasure from social interaction, and they’re quite socially skilled.”

Simon said that the team also noted that the children’s social deficits might be more a function of their developmental delay and intellectual disability than autism.

“If you put them with their younger siblings’ friends they function very well in a social setting,” Simon continued, “and they interact well with an adult who accommodates their expectations for social interaction.”

Angkustsiri said that further study is needed to assess more appropriate treatments for children with 22q, such as improving their communication skills, treating their anxiety, helping them to remain focused and on task.

 “There are a variety of different avenues that might be pursued rather than treatments that are designed to treat children with autism,” Angkustsiri said. “There are readily available, evidence-based treatments that may be more appropriate to help maximize these children’s potential.”

(Source: ucdmc.ucdavis.edu)

Scientists at the Centre for Addiction and Mental Health (CAMH) and University Health Network (UHN) have found a new link between early-onset Parkinson’s disease and a piece of DNA missing from chromosome 22. The findings help shed new light on the molecular changes that lead to Parkinson’s disease.

The study appears online today in JAMA Neurology.

Among people aged 35 to 64 who were missing DNA from a specific part of chromosome 22, the research team found a marked increase in the number of cases of Parkinson’s disease, compared to expected rates of Parkinson’s disease in the general population from the same age group.

The deletion, which occurs when a person is born with about 50 genes missing on one chromosome 22, is associated with 22q11.2 deletion syndrome. People with this condition may have heart or other birth defects, learning or speech difficulties, and some develop schizophrenia. It occurs in an estimated 1 in 2,000 to 4,000 births, but is believed to be under-diagnosed.

“22q11.2 deletion syndrome has been fairly well studied in childhood and adolescence, but less is known about its effects as people age,” said Dr. Anne Bassett, Director of CAMH’s Clinical Genetics Research Program and Director of the Dalglish Family Hearts and Minds Clinic at UHN, the world’s first clinic dedicated to adults with 22q11.2 deletion syndrome. A few cases of patients with the syndrome who had Parkinson’s disease symptoms had been previously reported, which suggested that the two conditions might be linked.

Parkinson’s disease is one of the most common neurodegenerative disorders worldwide, typically affecting people over the age of 65. Earlier onset of Parkinson’s disease, before age 50, is rare and has been associated with several other genetic changes that are not on chromosome 22.

The researchers studied 159 adults with 22q11.2 deletion syndrome to discover how many had been clinically diagnosed with Parkinson’s disease. For three individuals with the deletion and Parkinson’s disease who were deceased, brain tissue was also examined.

“Through a post-mortem examination, we were able to show that all three patients had a loss of neurons that was typical of that seen in Parkinson’s disease. The examination also helped to show that the symptoms of Parkinson’s disease were not related to side effects of the medications commonly used to treat schizophrenia,” added Dr.Rasmus Kiehl, neuropathologist in UHN’s Laboratory Medicine Program, who co-authored the report with CAMH graduate student Nancy Butcher. The team also found that Parkinson’s disease in 22q11.2 deletion syndrome is associated with abnormal accumulations of protein called Lewy bodies in the brain in some, but not all cases, just as in another genetic form of Parkinson’s disease.

The findings highlight the complexity of clinical care when both Parkinson’s disease and 22q11.2 deletion syndrome are present. “Our results may inform best practices in the clinic in these cases,” said Dr. Bassett, Senior Scientist in CAMH’s Campbell Family Mental Health Research Institute.

Because patients with 22q11.2DS who have schizophrenia are often prescribed anti-psychotic medications, they may experience side-effects such as tremors and muscle stiffness, similar to symptoms of Parkinson’s disease.

As a result, the researchers found that anti-psychotic use delayed the diagnosis of Parkinson’s disease – and the opportunity for treatment – by up to 10 years.

For people with early-onset Parkinson’s disease, who also have other features that could indicate 22q11.2 deletion syndrome, clinical genetic testing for the deletion on chromosome 22 should be considered, the researchers suggest.

“Our discovery that the 22q11.2 deletion syndrome is associated with Parkinson’s disease is very exciting,” said Dr. Anthony Lang, Director of the Movement Disorders Program at the Krembil Neuroscience Centre of Toronto Western Hospital. “The varying pathology that we found is reminiscent of certain other genetic causes of Parkinson’s disease, and opens new directions to search for novel genes that could cause its more common form. Studies of patients with 22q11.2 deletion syndrome before they ever develop clinical features of Parkinson’s disease may not only provide important information on the effectiveness of screening methods for early detection of the disease, but also allow for future ‘neuroprotective treatments’ to be introduced at the ultimate time when they can have a chance to make an important impact on preventing the disease or slowing its course.” 

“Most people with 22q11.2 deletion syndrome will not develop Parkinson’s disease,” emphasizes Dr. Bassett. “But it does occur at a rate higher than in the general population. We will now be on the look-out for this so we can provide the best care for patients.”

(Source: camh.ca)