Two novel mouse models mimicking minor deletions in 22q11.2 deletion syndrome revealed the contribution of each deleted region to psychiatric disorders.

22q11.2 deletion syndrome (22q11.2DS) is a disorder caused by the segmental deletion of human chromosome 22. This chromosomal deletion is known as high genetic risk factors for various psychiatric disorders. The different deletion types are identified in 22q11.2DS patients, including the most common 3.0-Mb deletion, and the less-frequent 1.5-Mb and 1.4-Mb deletions. In previous animal studies of psychiatric disorders associated with 22q11.2DS mainly focused on the 1.5-Mb deletion and model mice mimicking the human 1.5-Mb deletion have been established with diverse genetic backgrounds, which resulted in the contradictory phenotypes. On the other hand, the contribution of the genes in 1.4-Mb region to psychiatric disorders is poorly understood. In this study, we generated two mouse lines that reproduced the 1.4-Mb and 1.5-Mb deletions of 22q11.2DS [Del(1.4 Mb)/+ and Del(1.5 Mb)/+] on the pure C57BL/6N genetic background. These mutant mice were analyzed comprehensively by behavioral tests, such as measurement of locomotor activity, sociability, prepulse inhibition and fear-conditioning memory. Del(1.4 Mb)/+ mice displayed decreased locomotor activity, but no abnormalities were observed in all other behavioral tests. Del(1.5 Mb)/+ mice showed reduction of prepulse inhibition and impairment of contextual- and cued-dependent fear memory, which is consistent with previous reports. Furthermore, apparently intact social recognition in Del(1.4 Mb)/+ and Del(1.5 Mb)/+ mice suggests that the impaired social recognition observed in Del(3.0 Mb)/+ mice mimicking the human 3.0-Mb deletion requires mutations both in 1.4-Mb and 1.5 Mb regions. Our previous study has shown that Del(3.0 Mb)/+ mice presented disturbance of behavioral circadian rhythm. Therefore, we further evaluated sleep/wakefulness cycles in Del(3.0 Mb)/+ mice by electroencephalogram (EEG) and electromyogram (EMG) recording. EEG/EMG analysis revealed the disturbed wakefulness and non-rapid eye moving sleep (NREMS) cycles in Del(3.0 Mb)/+ mice, suggesting that Del(3.0 Mb)/+ mice may be unable to maintain their wakefulness. Together, our mouse models deepen our understanding of genetic contributions to schizophrenic phenotypes related to 22q11.2DS.

Sleep patterns and problems among children with 22q11 deletion syndrome.

BACKGROUND: To delineate sleep habits and problems in children with 22q11.2 deletion syndrome (22q11DS). METHODS: Thirty children, age 1-15 (mean 6.8) years, participated in the study, which was an internet-based anonymous survey of parents of children with 22q11DS administered via the 22q11.2 Foundation. The main outcome was the Childhood Sleep Habits Questionnaire (CSHQ). RESULTS: Scores on the CSHQ demonstrated clinically significant sleep problems in 29 of the 30 children. When compared with previously reported normative values for typically developing children of the same age, children with 22q11DS had significantly greater sleep problems. Only 30% of children had previously undergone sleep study. While about half of children had tried a medication for sleep, it usually was not felt to be helpful. In contrast, parents reported that behavioral interventions, such as consistent bedtime routine and appropriate sleep environment, were helpful. This is one of the first studies to specifically address sleep problems other than obstructive sleep apnea in children with 22q11DS. CONCLUSIONS: The findings suggest children with 22q11DS may have a higher risk of experiencing clinical sleep problems, compared to typically developing children. Consideration of additional screening and treatment of sleep disorders in children with 22q11DS is warranted.

Seeing Eye to Eye With Threat: Atypical Threat Bias in Children With 22q11.2 Deletion Syndrome.

Individuals with 22q11.2 deletion syndrome (22q11DS) show high rates of anxiety associated with their increased risk of developing schizophrenia. Biased attention is associated with anxiety and is important to investigate in those with 22q11DS given this association. We analyzed attention bias to emotional faces in 7- to 17-year olds with 22q11DS and typically developing controls (TD) using a dot probe threat bias paradigm. We measured response time, eye tracking, and pupilometry. Those with 22q11DS showed no significant changes in early versus late trials, whereas those who were TD showed differing patterns in both gaze and pupilometry over time. The patterns in those who are TD may indicate adaptation that is lacking or slower in individuals with 22q11DS.

Neurocognitive profile and onset of psychosis symptoms in children, adolescents and young adults with 22q11 deletion syndrome: A longitudinal study.

BACKGROUND: The neurobehavioral phenotype of 22q11.2 deletion syndrome (22q11DS) includes cognitive dysfunction and high rates of psychotic symptoms and schizophrenia. Existing research has mainly considered changes in IQ, especially its decline, as a psychosis predictor. The aim of this study was to investigate, in a longitudinal perspective, the relationship between neuropsychological abilities (not only IQ but also executive functioning, language and visual-motor integration abilities) and onset of psychotic symptoms in a sample of children, adolescents and young adults with 22q11DS. In addition, the role of comorbid psychiatric disorders at baseline was taken into account. METHODS: 75 participants with 22q11DS, aged between 6 and 27 years at baseline, were included. Eighteen of the 75 participants had developed psychosis at the one year follow-up (onset psychosis-OP) and constituted the first group; 57 participants who had not developed a psychosis at the one year follow-up (without onset psychosis-WOP) constituted the second group. RESULTS: At baseline, group OP showed lower IQ (both full scale and verbal and performance scale) and more perseverative errors as well as a reduced number of correct categories on the Wisconsin Card Sorting Test (WCST) compared to group WOP. In addition, at baseline, group OP showed a higher frequency of depressive disorders than group WOP. CONCLUSION: Even if with caution, results suggest neuropsychological deficits and depressive symptoms should be considered and monitored as possible clinical signs for the onset of psychosis in children, adolescents and young adults with 22q11DS.

The 22q11.2 deletion syndrome as a model for idiopathic scoliosis - A hypothesis.

Adolescent idiopathic scoliosis (AIS), defined as a lateral deviation of the spine of at least ten degrees, is a classic enigma in orthopaedics and affects 1-4% of the general population. Despite (over) a century of intensive research, the etiology is still largely unknown. One of the major problems in all existing AIS research is the fact that most patients come to medical attention after onset of the curve. Therefore, it is impossible to know whether current investigated parameters are causative, or an effect of the scoliosis. Moreover, up until now there is no known animal model that captures the core features of AIS. In order to identify causal pathways leading to AIS we propose another approach, which has been of great value in other medical disciplines: To use a subset of the population, with a higher risk for a certain disease as a "model" for the general population. Such a "model" may allow the identification of causative mechanisms that might be applicable to the general population. The 22q11.2 deletion syndrome (22q11.2DS) is the most common microdeletion syndrome and occurs in ∼1:3000-6000 children and 1:1000 pregnancies. Nearly half of the population of patients with 22q11.2DS develop a scoliosis that in most cases resembles AIS as far as age at onset and curve pattern. We postulate that within 22q11.2DS certain causal pathways leading to scoliosis can be identified and that these are applicable to the general population.

Individuals with 22q11.2 deletion syndrome show intact prediction but reduced adaptation in responses to repeated sounds: Evidence from Bayesian mapping.

One of the most common copy number variants, the 22q11.2 microdeletion, confers an increased risk for schizophrenia. Since schizophrenia has been associated with an aberrant neural response to repeated stimuli through both reduced adaptation and prediction, we here hypothesized that this may also be the case in nonpsychotic individuals with a 22q11.2 deletion. We recorded high-density EEG from 19 individuals with 22q11.2 deletion syndrome (12-25 years), as well as 27 healthy volunteers with comparable age and sex distribution, while they listened to a sequence of sounds arranged in a roving oddball paradigm. Using posterior probability maps and dynamic causal modelling we tested three different models accounting for repetition dependent changes in cortical responses as well as in effective connectivity; namely an adaptation model, a prediction model, and a model including both adaptation and prediction. Repetition-dependent changes were parametrically modulated by a combination of adaptation and prediction and were apparent in both cortical responses and in the underlying effective connectivity. This effect was reduced in individuals with a 22q11.2 deletion and was negatively correlated with negative symptom severity. Follow-up analysis showed that the reduced effect of the combined adaptation and prediction model seen in individuals with 22q11.2 deletion was driven by reduced adaptation rather than prediction failure. Our findings suggest that adaptation is reduced in individuals with a 22q11.2 deletion, which can be interpreted in light of the framework of predictive coding as a failure to suppress prediction errors.

[Voice and speech of children with 22q11 deletion syndrome]. / Voz y habla de los niños con sindrome de delecion de 22q11.

INTRODUCTION: The 22q11 deletion syndrome (S22q11) is a genetic disorder caused by the loss of a fragment of the chromosome 22. The clinical manifestations associated with the syndrome are diverse, including learning difficulties and alterations in voice, speech and language. However, to date we have not found any study that evaluates these aspects in the Spanish population with S22q11. PATIENTS AND METHODS: We evaluate the voice and speech of a sample of 10 boys and 7 girls, aged 3 years and 3 months to 13 years and 9 months old (mean age: 9,4 ± 3,5 years old) with S22q11, with voice recordings and a phonological and phonetic evaluation. Also, semistructured type interview is administered to parents. RESULTS: Most children of our series, both male and female, with S22q11 have a deeper voice than expected by gender and age, except for male children over 12 years. In terms of intensity, all of them are within the parameters of normality in spontaneous conversation. Almost all of them showed alterations in voice quality, mainly due to hypernasality. Regarding the speech, there are major difficulties in the articulation of fricatives, affricates and vibrant rhotic consonant clusters + /r/. Likewise, children, especially the youngest ones, make use of glottal stops to replace consonants. CONCLUSIONS: In the studied sample, most of the children with S22q11 have specific voice and speech alterations.

TITLE: Voz y habla de los niños con sindrome de delecion de 22q11.Introduccion. El sindrome de delecion de 22q11 (S22q11) es un trastorno genetico causado por la perdida de un fragmento del cromosoma 22. Las manifestaciones clinicas que presenta quien lo padece son diversas, incluyendo dificultades del aprendizaje y alteraciones de la voz, el habla y el lenguaje. No obstante, hasta ahora no hemos encontrado ningun estudio que evalue estos aspectos en la poblacion española con el S22q11. Pacientes y metodos. Se evalua la voz y el habla de una muestra de 10 niños y 7 niñas, de 3 años y 3 meses a 13 años y 9 meses (edad media: 9,4 ± 3,5 años), con el S22q11, a traves de registros de voz y de una prueba de evaluacion fonologica y fonetica. Ademas, se realiza una entrevista semiestructurada a los padres. Resultados. La mayoria de los niños y las niñas con el S22q11 tienen una voz mas grave de lo esperable por su sexo y edad, a excepcion de los niños varones con mas de 12 años. En cuanto a la intensidad, todos ellos se encuentran dentro de los parametros de normalidad en la conversacion espontanea. Todos presentan alteraciones del timbre, principalmente por hipernasalidad. Respecto al habla, hay mayores dificultades en la articulacion de las fricativas, las africadas, la rotica vibrante (/r/) y los grupos consonanticos + /r/. Asimismo, los niños, sobre todo los mas pequeños, utilizan las oclusivas gloticas para sustituir consonantes. Conclusiones. En la muestra estudiada, la mayoria de los niños con el S22q11 presenta alteraciones especificas tanto de la voz como del habla.

Consideraciones anestésicas en pacientes con microdeleción del cromosoma 22q11 / Anesthetic issues in patients mycrodeletion syndrome produced by the deletion of chromosome 22q11

The syndrome produced by the deletion of chromosome 22q11 corresponds to a pattern of anomalies that occurs when a specific region of chromosome 22 is lost, specifically called 22q11.2. This microdeletion corresponds to the most frequent chromosomal alteration in humans, which has a prevalence of 1 per 4,000 live births. This includes a great variety of phenotypes, many of them subclinical, among which the Di George syndrome and the Velocardiofacial syndrome stand out. The main cause of mortality is of cardiac origin. Embryologically, this microdeletion is associated with alterations in the differentiation and migration of the pharyngeal system, with consequent craniofacial, cardiac, airway, thymus and parathyroid alterations, among others. In this sense, these patients present a higher risk of complications such as inmunodeficiency, hypocalcemia and hemorrhagic risk. From the surgical and anesthetic point of view, they can present cardiopathies of greater complexity of correction, which in some cases is also related to anatomical airway alterations which can constitute an important challenge when operating this type of patients. Considering the above, there is an increase in perioperative risk which could increase mortality. The objective of this review is to present the characteristics and behavior of this group of patients in the correction of their heart diseases, so that they are known by the anesthesiologists who work in the cardiovascular area.

El síndrome de microdeleción 22q11 corresponde a un patrón de anomalías que se produce al perderse una región específica del cromosoma 22, específicamente llamada 22q11.2. Esta microdeleción corresponde a la alteración genética más frecuente en humanos la cual tiene una prevalencia de 1 cada 4.000 recién nacidos vivos. Incluye una gran variedad de fenotipos, muchos de ellos subclínicos, entre los que destaca el síndrome Di George y el síndrome Velocardiofacial. La principal causa de mortalidad es de origen cardíaco. Embriológicamente la microdeleción se asocia a alteraciones en diferenciación y migración del aparato faríngeo, con las consiguientes alteraciones cráneo-faciales, cardíacas, de vía aérea, timo y paratiroides, entre otras. En ese sentido, presentan mayor frecuencia de complicaciones tales como infecciones, hipocalcemia y riesgo hemorrágico. Desde el punto de vista quirúrgico y anestésico pueden presentar cardiopatías de mayor complejidad de corrección, asociado o no a alteraciones anatómicas en vía aérea lo que puede constituir un importante desafío al momento de intervenir. Lo anterior aumenta el riesgo perioperatorio, lo que podría derivar en aumento de la mortalidad. El objetivo de esta revisión es presentar las características y comportamiento de este grupo de pacientes en la corrección de sus cardiopatías, de modo que sean un aporte para los anestesiólogos que se desempeñan en el área cardiovascular.

Musical auditory processing, cognition, and psychopathology in 22q11.2 deletion syndrome.

Chromosome 22q11.2 deletion syndrome (22q11DS) is associated with impairment in multiple domains of cognition and risk for several psychiatric disorders. Musical auditory processing is highly heritable, and is impaired in individuals with schizophrenia and other neurodevelopmental disorders, but has never been studied in 22q11DS, notwithstanding anecdotal evidence of its sparing. We aimed to characterize musical auditory processing in 22q11DS and explore potential relationships with other cognitive domains, musical engagement, and psychiatric disorders. The Distorted Tunes Task and Global Musical Sophistication Index were used to assess pitch discrimination and general musical engagement in 58 individuals with 22q11DS aged 8-29 years. Psychopathology was assessed with sections from the modified Schedule for Affective Disorders and Schizophrenia for School-Age Children and the Structured Interview for Prodromal Syndromes. The Penn computerized neurocognitive battery (CNB) examined four domains of cognition (executive functioning, episodic memory, complex cognition, and social cognition). Significant musical auditory processing impairment and reduced musical engagement were found in individuals with 22q11DS. However, deficits in musical auditory processing were not associated with reduced musical engagement. After covarying for age and sex, episodic memory and overall CNB performance accuracy were significantly related to performance in musical auditory processing. There were no relationships between musical auditory processing and presence of any psychiatric diagnoses. Individuals with 22q11DS experience significant deficits in musical auditory processing and reduced musical engagement. Pitch discrimination is associated with overall cognitive ability, but appears to be largely independent of psychiatric illness.

Olfactory deficits and psychosis-spectrum symptoms in 22q11.2 deletion syndrome.

Olfactory functioning is a promising biomarker for psychosis in 22q11.2 deletion syndrome (22q11DS) but has not been well studied to date. This is a pilot effort to evaluate the potential for tests of olfactory functioning to contribute to risk and resilience prediction in 22q11DS, and is the first study to evaluate relationships among olfactory deficits, cognition and psychosis-spectrum symptoms. Odor identification and discrimination were evaluated in 32 individuals with 22q11DS and 110 healthy comparison subjects (HC). Individuals with 22q11DS also underwent cognitive testing with the Penn Computerized Neurocognitive Battery, which evaluates executive functioning, episodic memory, complex cognition, and social cognition. Positive, negative, disorganized and general psychosis-spectrum symptoms were rated according to the Scale of Prodromal Symptoms. Age-normalized scores were calculated for odor identification and discrimination based on normative data. Both odor identification (p < 0.001, Cohen's d = -2.15, 95% CI [-2.62, -1.68]) and discrimination (p < 0.001, Cohen's d = -1.81, 95% CI [-2.26, -1.35]) were significantly impaired in 22q11DS relative to HC. There were no sex differences in either group. Neither odor identification nor discrimination was correlated with overall cognition or any specific cognitive domain in 22q11DS. Impairment in odor discrimination was correlated with higher negative and overall psychosis-spectrum symptoms. There was no significant effect of catechol-O-methyltransferase Val(158)Met genotype or presence of velopharyngeal insufficiency on olfactory functioning. Olfactory deficits, particularly olfactory discrimination, are robust in 22q11DS and appear to be independent of cognitive deficits. They are also clinically relevant and related to psychosis-spectrum symptoms. Olfactory functioning appears to be a promising biomarker for psychosis in 22q11DS.

Visual perception skills: a comparison between patients with Noonan syndrome and 22q11.2 deletion syndrome.

Ventral and dorsal streams are visual pathways deputed to transmit information from the photoreceptors of the retina to the lateral geniculate nucleus and then to the primary visual cortex (V1). Several studies investigated whether one pathway is more vulnerable than the other during development, and whether these streams develop at different rates. The results are still discordant. The aim of the present study was to understand the functionality of the dorsal and the ventral streams in two populations affected by different genetic disorders, Noonan syndrome (NS) and 22q11.2 deletion syndrome (22q11.2DS), and explore the possible genotype-phenotype relationships. 'Form coherence' abilities for the ventral stream and 'motion coherence' abilities for the dorsal stream were evaluated in 19 participants with NS and 20 participants with 22q11.2DS. Collected data were compared with 55 age-matched controls. Participants with NS and 22q11.2DS did not differ in the form coherence task, and their performance was significantly lower than that of controls. However, in the motion coherence task, the group with NS and controls did not differ, and both obtained significantly higher scores than the group with 22q11.2DS. Our findings indicate that deficits in the dorsal stream are related to the specific genotype, and that in our syndromic groups the ventral stream is more vulnerable than the dorsal stream.

No age effect in the prevalence and clinical significance of ultra-high risk symptoms and criteria for psychosis in 22q11 deletion syndrome: Confirmation of the genetically driven risk for psychosis?

BACKGROUND: The 22q11.2 deletion syndrome (22q11DS) is one of the highest known risk factors for schizophrenia. Thus, the detection of 22q11DS patients at particularly high risk of psychosis is important, yet studies on the clinical significance of the widely used ultra-high risk (UHR) criteria in 22q11DS are inconclusive. Since age was reported to moderate clinical significance of UHR symptoms in community samples, we explored whether age at presentation of UHR symptoms and criteria may explain part of this heterogeneity. METHODS: 111 patients with 22q11DS (8-30 years; 15.7±4.7) were assessed for UHR symptoms/criteria. Information on diagnoses, psychosocial functioning, and IQ were collected. RESULTS: Any UHR symptom was reported by 38.7%, any UHR criterion by 27%. No significant influence of age on the prevalence of UHR symptoms or criteria was detected. Moreover, age did not significantly modulate the association between UHR symptoms and functioning. However, significant interaction terms suggested that younger age groups were more likely to meet UHR criteria in the presence of UHR symptoms compared to the adult group. DISCUSSION: Compared to the general population, prevalence of UHR symptoms and criteria was 3.8-fold and 20.8-fold in our 22q11DS sample. Contrary to the general population, age only modulated the prevalence of UHR criteria among those with UHR symptoms, but not their prevalence per se or their clinical significance. This suggests that UHR symptoms might develop as a trait factor in terms of a genetically driven schizotypal disposition in 22q11DS, thus necessitating future studies on psychosis-risk indicators in this genetic high-risk group.

Growth characteristics and endocrine abnormalities in 22q11.2 deletion syndrome.

22q11.2 deletion syndrome (22q11.2DS) has a wide range of clinical features including endocrine abnormalities. We aimed to characterize growth patterns, hypoparathyroidism, and thyroid dysfunction of individuals with 22q11.2DS. Anthropometric and laboratory measurements were obtained from the charts of 48 individuals (males=28, 8.0±6.8 visits/participant) followed at a national 22q11.2DS clinic between 2009 and 2016. Age at diagnosis was 4.3±4.9 years and age at last evaluation 11.2±7.2 years. Median height-SDS was negative at all ages. Height-SDS at last visit was correlated to the midparental height-SDS (r=0.52 P=0.002). Yet, participants did not reach their target height, with a difference of 1.06±1.07 SD (P <0.0001). Height-SDS at last visit of participants with a heart defect was lower compared to participants with a normal heart (-1.5±1.4 vs. -0.6±0.8, P=0.036), with lower height-SDS in the subgroup of participants with severe heart defects (-2.1±1.6, P=0.009). Mean IGF1-SDS was low (-0.99±1.68) but was not correlated with height-SDS. Thirteen patients (27%) had hypoparathyroidism: 10 presented during infancy and 3 during adolescence. Five patients (10.4%, female=4) had thyroid abnormalities. In conclusions, individuals with 22q11.2 DS have a distinct growth pattern consisting of growth restriction at all ages, resulting in final adult height in the low-normal range. Hypoparathyroidism is common and may present during the neonatal period as well as later in life. Thyroid abnormalities may present during childhood, adolescence, or adulthood.

Frontal Hypoactivation During a Working Memory Task in Children With 22q11 Deletion Syndrome.

Impairments in executive function, such as working memory, are almost universal in children with chromosome 22q11.2 deletion syndrome. Delineating the neural underpinnings of these functions would enhance understanding of these impairments. In this study, children and adolescents with 22q11 deletion syndrome were compared with healthy control participants in a functional magnetic resonance imaging (MRI) study of working memory. When the 2-back condition was contrasted with the 1-back and 0-back conditions, the participants with 22q11 deletion syndrome showed lower activation in several brain areas involved in working memory-notably dorsolateral prefrontal cortex, anterior cingulate, and precuneus. This hypoactivation may be due to reduced gray matter volumes or white matter connectivity in the frontal and parietal regions, differences that have previously been documented in children with 22q11 deletion syndrome. Understanding differences in brain function will provide a foundation for future interventions to address the wide range of neurodevelopmental deficits observed in 22q11 deletion syndrome.

Multimodal MRI reveals structural connectivity differences in 22q11 deletion syndrome related to impaired spatial working memory.

INTRODUCTION: Impaired spatial working memory is a core cognitive deficit observed in people with 22q11 Deletion syndrome (22q11DS) and has been suggested as a candidate endophenotype for schizophrenia. However, to date, the neuroanatomical mechanisms describing its structural and functional underpinnings in 22q11DS remain unclear. We quantitatively investigate the cognitive processes and associated neuroanatomy of spatial working memory in people with 22q11DS compared to matched controls. We examine whether there are significant between-group differences in spatial working memory using task related fMRI, Voxel based morphometry and white matter fiber tractography. MATERIALS AND METHODS: Multimodal magnetic resonance imaging employing functional, diffusion and volumetric techniques were used to quantitatively assess the cognitive and neuroanatomical features of spatial working memory processes in 22q11DS. Twenty-six participants with genetically confirmed 22q11DS aged between 9 and 52 years and 26 controls aged between 8 and 46 years, matched for age, gender, and handedness were recruited. RESULTS: People with 22q11DS have significant differences in spatial working memory functioning accompanied by a gray matter volume reduction in the right precuneus. Gray matter volume was significantly correlated with task performance scores in these areas. Tractography revealed extensive differences along fibers between task-related cortical activations with pronounced differences localized to interhemispheric commissural fibers within the parietal section of the corpus callosum. CONCLUSIONS: Abnormal spatial working memory in 22q11DS is associated with aberrant functional activity in conjunction with gray and white matter structural abnormalities. These anomalies in discrete brain regions may increase susceptibility to the development of psychiatric disorders such as schizophrenia. Hum Brain Mapp 37:4689-4705, 2016. © 2016 Wiley Periodicals, Inc.

Early-onset Parkinson's Disease Associated with Chromosome 22q11.2 Deletion Syndrome.

We herein report the case of a 43-year-old man with a 4-year history of resting tremor and akinesia. His resting tremor and rigidity were more prominent on the left side. He also presented retropulsion. His symptoms responded to the administration of levodopa. The patient also had a cleft lip and palate, cavum vergae, and hypoparathyroidism. A chromosome analysis disclosed a hemizygous deletion in 22q11.2, and he was diagnosed with early-onset Parkinson's disease associated with 22q11.2 deletion syndrome. However, the patient lacked autonomic nerve dysfunction, and his cardiac uptake of (123)I-metaiodobenzylguanidine was normal, indicating an underlying pathological mechanism that differed to that of sporadic Parkinson's disease.

The Effect of Loudness Variation on Velopharyngeal Function in Children with 22q11.2 Deletion Syndrome: A Pilot Study.

OBJECTIVE: Children with 22q11.2 deletion syndrome (22qDS) often require surgical intervention to treat velopharyngeal dysfunction (VPD). Although some studies have documented improved velopharyngeal (VP) closure under increased speaking effort, currently no studies have examined the effect of similar behavioral speech modifications on VP closure in children with 22qDS. The purpose of this pilot study was to explore the effect of loudness on VP closure during speech in children with 22qDS and persisting VPD. PATIENTS AND METHODS: Four children with 22qDS, posterior pharyngeal flap, and persisting mild VPD underwent pressure-flow testing while repeating words at habitual and increased loudness levels. Using a single-subject A-B design, descriptive statistics and graphical measures were used to examine differences in VP orifice area (VPA) and timing of closure in the habitual versus loud condition. RESULTS: Results were mixed. Median VPA decreased during some stimuli for 3 participants, but increased for 1 subject when speaking louder. Median duration of nasal airflow decreased for 3 participants in the loud condition. CONCLUSION: This study presents preliminary aerodynamic data regarding the plasticity of VP physiology in the 22qDS group. Further research is needed to determine how loudness impacts VP function in children with 22qDS.

[Catch-22? Wide variety of phenotypes associated with the chromosome 22q11 deletion syndrome in two patients]. / A 22-es csapdája? A 22q11 kromoszóma deletiós szindróma változatos klinikai megjelenése két eset kapcsán.

The chromosome 22q11 deletion syndrome may present with a variety of phenotypes. Its symptoms generally include a characteristic facial dysmorphisms and multiplex developmental disorders. Fluorescence in situ hybridization is the current method of choice for the diagnosis if typical multiple defects and/or symptoms are present. The authors present the history of two patients who were followed-up for minor anomalies and various developmental disorders for several years in the genetic counseling office of the authors, but definitive diagnosis was not established. However, when DNA samples of the two patients were recently tested with array comparative genome hybridization, a diagnostic method which has already been used in their institute for several years, the results indicated deletion of the 11.2 region on the long arm of chromosome 22 in both patients. The authors draw attention to the incidence and wide phenotypic spectrum of the chromosome 22q11 deletion syndrome, and show that its identification can be aided with the novel molecular cytogenetic method available in their laboratory.