Olfactory Disorder in Children With 22q11 Deletion Syndrome

Abstract

OBJECTIVE-22q11 deletion syndrome, a common human interstitial deletion syndrome (1:5000), is associated with a heterogeneous physical phenotype, including several factors that markedly increase the risk for olfactory disorder. Despite its potential consequences, pediatric studies of impaired olfaction are rare, and odor detection in children with 22q11 deletion syndrome has not yet been examined. METHODS-TheUniversity of Pennsylvania Smell Identification Test was administered to 62 children, including 39 with 22q11 deletion syndrome and 23 neurotypical control siblings who ranged in age from 5.3 to 14.8 years. Lowered smell detection accuracy among affected children was predicted.RESULTS-Substantially more children with 22q11 deletion syndrome (68%) as compared with neurotypical control subjects (13%) had University of Pennsylvania Smell Identification Test scores ≥2 SDs below the standardization sample mean. Frequency of impairment in younger versus older children did not differ. The score distributions of children with and without velopharyngeal insufficiency did not differ; however, markedly lower score variance among children with velopharyngeal insufficiency suggested its negative impact on olfaction. Posthoc error analyses revealed that affected children had special difficulty detecting smells that are associated with fumes and smoke.CONCLUSIONS-Odor detection failures are ubiquitous among children with 22q11 deletion syndrome and are not associated with developmental delay or performance characteristics of younger affected children. Additional studies are needed to examine further the impact on olfaction of velopharyngeal insufficiency and compromised nasal airway patency. Children with 22q11 deletion syndrome should be evaluated routinely for olfactory disorder. When deficits are identified, caregivers should be warned of potential dangers that are associated with this type of sensory impairment. 22Q11 DELETION SYNDROME (22q11DS), also referred to as DiGeorge or velocardiofacial syndrome, results from a meiotic deletion at the q11.2 site on chromosome 22. It is estimated to occur in at least 1:5000 live births 1 and may be substantially more prevalent. 2 22q11DS results in the loss of ~30 gene copies 3 and a broadly heterogeneous physical phenotype, most typically including structural velopharyngeal anomalies, craniofacial or heart anomalies, and/ or immunologic deficits secondary to thymic irregularities. 4 Interest in the early neurologic and neurocognitive development of children with 22q11DS increased dramatically after reports of higher-than-expected rates of schizophrenia among affected adults. 5Clues regarding the source of neurocognitive differences in 22q11DS may reside in its genetic profile. Among the 30 deleted gene copies are 4 that have a direct and an indirect impact on production and release of glutamate, γ-aminobutyric acid (GABA), and dopa-mine, the 3 neurotransmitters that selectively subserve pathways that link basal ganglia and frontal/ prefrontal cortex 6 and that are impli...

Fetal phenotype associated with the 22q11 deletion

“…To date, this malformation has never been reported in the literature in the context of 22q11 deletion. However, a pediatric study [Sobin et al, ] identified a specific difficulty in detecting smells associated with fumes and smoke in 39 children with 22q11 deletions. An evaluation for olfactory disorders could thus be of interest when examining children with 22q11 deletion.…”

Evidence of Olfactory Deficits as Part of the Phenotypic Spectrum of Nonsyndromic Orofacial Clefting

“…27 Most critically, safety hazards exist for individuals with olfactory dysfunction. Hyposmia and anosmia have been demonstrated to reduce the ability to correctly identify smoke and noxious fumes, 7 possibly delaying the response to life threatening situations.…”

“…Individuals with velocardiofacial syndrome, for example, demonstrate a significant decrease in the ability to correctly identify specific odors (e.g., smoke) compared with controls. 7 Kallmann syndrome (OMIM#147950) is characterized by anosmia as well as occasional clefting of the primary and/or secondary palate. 8 Mutations in FGFR1 , a gene involved in olfactory bulb morphogenesis, 9,10 have been identified in Kallmann syndrome cases 11 as well as cases of nonsyndromic clefting.…”

Converging levels of analysis on a genomic hotspot for psychosis: Insights from 22q11.2 Deletion Syndrome

“…22qDS is characterized by a diverse assortment of neurocognitive deficits, ranging from overall reduced IQ, to abnormal results on assays of more specific endophenotypes such as prepulse inhibition (Kiley-Brabeck and Sobin, 2006; Sobin et al, 2005a, 2005b; Vorstman et al, 2009a; Vorstman et al, 2009b) tasks of spatial and attention-switching (Simon et al, 2005a; Sobin et al, 2006), and time perception (Drew et al, 2011). Although 22qDS patients have lower Full Scale IQ relative to typically developing children, verbal skills tend to be better preserved than non-verbal skills on both IQ and academic achievement measures in children with 22qDS (Bearden et al, 2001b; Moss et al, 1999; Swillen et al, 1999).…”