22q11.2 Deletion Syndrome: Are Motor Deficits More Than Expected for IQ Level?

doi:10.1016/j.jpeds.2010.04.073

The Journal of Pediatrics

Volume 157, Issue 4, October 2010, Pages 658-661

https://doi.org/10.1016/j.jpeds.2010.04.073 Get rights and content

Objective

To examine motor function in children with 22q11.2 deletion syndrome (22q11.2) and a Full Scale IQ (FSIQ) comparable control group.

Study design

This study was part of a prospective study of neuropsychological function in children 9 to 15 years of age with 22q11.2 and community control subjects and included children from these two populations with comparable FSIQs.

Results

Verbal IQs on the WISC-R for 40 children with 22q11.2 (88.4) and 24 community control subjects (87.2) were not different (P = .563). However, the performance IQs were (22q11.2; 81.1 vs community controls; 89.3; P < .001). On the Visual Motor Inventory, there was no difference between the standard scores of the two groups (22q11.2; 93.0 vs community control subjects; 98.1; P = .336) but on the motor coordination part of the Visual Motor Inventory, the scores of the 22q11.2 deletion syndrome group were lower (77.2 vs 89.3; P = .002). On the general neurologic examination (P = .906), the tone examination (P = .705), and the ball skills part of the Motor Battery, (P = .378), there were no differences. However, on the axial stability part of the Motor Battery, the children with 22q11.2 exhibited less good balance (P = .026).

Conclusions

School-aged children with 22q11.2 have specific motor deficits in axial stability and graphomotor skills.

Section snippets

Methods

Children with 22q11.2 and community controls were recruited through the Center for the Diagnosis, Treatment, and Study of Velo-Cardio-Facial Syndrome at the State University of New York–Upstate Medical University as part of a study of psychopathology in 22q11.2. All children in the 22q11.2 group had a FISH-confirmed deletion in the q11.2 locus of chromosome 22. The community control group was recruited from local public schools. Children with an identifiable genetic disorder or an identifiable

Results

The 22q11.2 group (n = 40) were younger (10.87 years [SD ± 2.49 years] vs 10.45 years [SD ± 2.66 years]; 2-tailed P = .0225) and of higher socioeconomic status (52.83 ± SD 10.16 vs 40.82 ± SD 13.25; 2-tailed P < .0001). Of the children with 22q11.2, 42.5% had ADHD compared with 35.2% of the control subjects (P = .347). With a discrepancy method to identify LD comparing Full Scale Intelligence Quotient (FSIQ) and Wechsler Individual Achievement Tests achievement test scores yielded only 3

Discussion

Our results support some clinical impressions and previous reports and dispute others. This data supports the clinical impression that children with 22q11.2 have axial instability. Although about a third of the children with 22q11.2 have low or very low tone, it was not significantly more common than the findings in the IQ-control group. Despite the low tone and axial instability, two-thirds of the children with 22q11.2 had ball skills in the normal range.

Several studies of younger children

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Cited by (23)

Updated clinical practice recommendations for managing children with 22q11.2 deletion syndrome
2023, Genetics in Medicine
This review aimed to update the clinical practice guidelines for managing children and adolescents with 22q11.2 deletion syndrome (22q11.2DS). The 22q11.2 Society, the international scientific organization studying chromosome 22q11.2 differences and related conditions, recruited expert clinicians worldwide to revise the original 2011 pediatric clinical practice guidelines in a stepwise process: (1) a systematic literature search (1992-2021), (2) study selection and data extraction by clinical experts from 9 different countries, covering 24 subspecialties, and (3) creation of a draft consensus document based on the literature and expert opinion, which was further shaped by survey results from family support organizations regarding perceived needs. Of 2441 22q11.2DS-relevant publications initially identified, 2344 received full-text reviews, including 1545 meeting criteria for potential relevance to clinical care of children and adolescents. Informed by the available literature, recommendations were formulated. Given evidence base limitations, multidisciplinary recommendations represent consensus statements of good practice for this evolving field. These recommendations provide contemporary guidance for evaluation, surveillance, and management of the many 22q11.2DS-associated physical, cognitive, behavioral, and psychiatric morbidities while addressing important genetic counseling and psychosocial issues.
Neurological features associated with 22q11.2 deletion syndrome
2022, The Chromosome 22q11.2 Deletion Syndrome: A Multidisciplinary Approach to Diagnosis and Treatment
A cross-comparison of cognitive ability across 8 genomic disorders
2021, Current Opinion in Genetics and Development
Citation Excerpt :
Using our search criteria, we identified 156 eligible studies that reported cognitive ability scores. This included 1 paper on 3q29 deletion [39], 36 papers on 7q11.23 deletion [32,40–74], 2 papers on 15q11.2 deletion (AS) [75,76], 31 papers on 15q11.2 deletion (PWS) [56,77–106], 6 papers on 16p11.2 deletion (proximal) [107–112], 4 papers on 16p11.2 duplication (proximal) [107,109,110,112], 3 papers on 17p11.2 deletion [113–115], and 73 papers on 22q11.2 deletion syndrome [74,80,116–186]. Studies reporting cognitive scores for 1q21.1 deletion, 2p15p16.1 deletion, and 9q34 deletion were not identified.
Genomic disorders result from rearrangement of the human genome. Most genomic disorders are caused by copy number variants (CNV), deletions or duplications of several hundred kilobases. Many CNV loci are associated with autism, schizophrenia, and most commonly, intellectual disability (ID). However, there is little comparison of cognitive ability measures across these CNV disorders. This study aims to understand whether existing data can be leveraged for a cross-comparison of cognitive ability among multiple CNV. We found there is a lack of harmonization among assessment instruments and little standardization for reporting summary data across studies. Despite these limitations, we identified a differential impact of CNV loci on cognitive ability. Our data suggest that future cross-comparisons of CNV disorders will reveal meaningful differences across the phenotypic spectrum, especially if standardized phenotypic assessment is achieved.
22q11.2 microdeletion syndrome: Analysis of the care pathway before the genetic diagnosis
2017, Archives de Pediatrie
Le syndrome microdélétionnel 22q11.2 (SMD22q11) est le microremaniement chromosomique le plus fréquent : 15 000 personnes seraient atteintes en France, plus de la moitié l’ignorant. L’objectif de cette étude était d’analyser le parcours de santé des patients porteurs d’un SMD22q11 avant leur diagnostic génétique.
Il s’agit d’une étude rétrospective, monocentrique, concernant les patients porteurs d’un SMD22q11 diagnostiqué entre janvier 2000 et décembre 2015 au centre hospitalier régional universitaire (CHRU) de Nancy. Seuls les éléments précédant le diagnostic génétique ont été recueillis.
Trente-deux patients ont été inclus. L’âge moyen au diagnostic était de 9 ans et 2 mois (médiane 2 ans et 11 mois). Une anomalie anténatale avait été signalée pour 15 grossesses. Les signes néonatals majeurs avaient été les difficultés alimentaires et les malformations (n = 20), principalement cardiaques (n = 16) les cardiopathies cono-troncales prédominant (n = 6). L’âge moyen au diagnostic en cas de malformation avait été de 3 ans et 3 mois. Avant 3 ans, 9 enfants avaient présenté un retard de langage. Après 3 ans, la rhinolalie avait été prédominante (n = 11). Les difficultés scolaires avaient été quasiment constantes. Le diagnostic avait été posé pour 4 des 7 adultes suite au diagnostic pour leur enfant. Les troubles relationnels avaient touché 8 patients. Le spécialiste évoquant le plus souvent le diagnostic avait été un cardiopédiatre (n = 9). Certains spécialistes médicaux et paramédicaux fréquemment consultés n’avaient jamais préconisé de consultation de génétique clinique.
L’hétérogénéité clinique du SMD22q11 nécessite une formation des professionnels de santé à la reconnaissance précoce des signes cliniques devant orienter vers le généticien.
22q11.2 deletion syndrome (22q11.2DS) is a very broad phenotypic spectrum disorder. It can affect many organs or systems. 22q11.2DS is the most common microdeletion syndrome in humans, with a prevalence ranging from one in every 2000 to one in 4000 newborns. It seems to be more prevalent than reported and under-recognized or undiagnosed because of its inherent clinical variability and heterogeneity. In France, 15,000 patients may be affected by this disease, more than half without knowing it. The aim of this study was to analyze the care pathway before the genetic diagnosis of 22q11.2DS.
We conducted a single-center, retrospective analysis of postnatally diagnosed patients recruited by the cytogenetic laboratory of Nancy (France) from January 2000 to December 2015. Clinical data were first collected by consulting the medical files of patients and then by calling them directly. Written informed consent was obtained and the study was approved by local research ethics boards.
Data concerned only clinical features before the diagnosis.
The cohort consisted of 32 individuals with 22q11.2DS. The average age at diagnosis was 9 years and 2 months and the median age was 2 years and 11 months. Fetal echography was abnormal in 15 pregnancies. During the neonatal period, the most important features were eating difficulties and congenital malformations (n = 20), with a majority of complex heart diseases (n = 16), dominated by conotruncal malformations (n = 6). In case of malformation, the average age at diagnosis decreased to 2 years and 6 months. A congenital heart disease brought the average age of diagnosis down to 2 years and 6 months. Hypocalcemia and dysmorphism were also classical features (n = 14). Before the age of 3 years, speech delay occurred in nine patients. After 3 years of age, rhinolalia was predominant (n = 11). Academic disabilities were present in all subjects. At least 14 patients had a de novo deletion. Five patients were diagnosed within genetic counseling, with the deletion was inherited from the mother in three out of four cases. One was the monozygotic twin of a patient. Seven patients were diagnosed as adults. Four of them were diagnosed only because of the clinical presentation of their children or fetuses. Retrospectively, all adult patients had clinical signs suggesting the 22q11.2DS diagnosis. Relational disorders affected eight patients. None of them had been referred to the geneticist for this reason. In most cases, the pediatric cardiologist referred patients to the geneticist (n = 9). Physiotherapists (n = 15) and speech-language pathologists (n = 12) were frequently requested but did not participate in the diagnosis.
The present study highlights the difficulty of establishing the diagnosis when the major features of the 22q11.2DS are absent during the 1st months of life. This is particularly true when there is no congenital defect. Special attention must be given to speech disorders in childhood and neuropsychological disorders later in life. The association between 22q11.2DS and early-onset parkinson disease implies that adult neurologists should be aware of this diagnosis. For adult patients, familial occurrence is the most frequent cause of diagnosis in spite of clinical signs suggestive of 22q11.2DS. The management of these patients involves better information of medical and paramedical staff in order to refer them to the geneticist earlier in life.
Functional outcomes of adults with 22q11.2 deletion syndrome
2012, Genetics in Medicine
The 22q11.2 deletion syndrome is a common multisystem genomic disorder with congenital and later-onset manifestations, including congenital heart disease, intellectual disability, and psychiatric illness, that may affect long-term functioning. There are limited data on adult functioning in 22q11.2 deletion syndrome.
We used the Vineland Adaptive Behavior Scales to assess functioning in 100 adults with 22q11.2 deletion syndrome (n = 46 male; mean age = 28.8 (standard deviation = 9.7) years) where intellect ranged from average to borderline (n = 57) to mild intellectual disability (n = 43).
More than 75% of the subjects scored in the functional deficit range. Although personal, vocational, and financial demographics confirmed widespread functional impairment, daily living skills and employment were relative strengths. Intelligence quotient was a significant predictor (P < 0.001) of overall and domain-specific adaptive functioning skills. A diagnosis of schizophrenia was a significant predictor (P < 0.05) of overall adaptive functioning, daily living skills, and socialization scores. Notably, congenital heart disease, history of mood/anxiety disorders, sex, and age were not significant predictors of functioning.
Despite functional impairment in adulthood that is primarily mediated by cognitive and psychiatric phenotypes, relative strengths in activities of daily living and employment have important implications for services and long-term planning. These results may help to inform expectations about outcomes for patients with 22q11.2 deletion syndrome.
Genet Med 2012:14(10):836–843
Relationship between reaction time, fine motor control, and visual-spatial perception on vigilance and visual-motor tasks in 22q11.2 Deletion Syndrome
2012, Research in Developmental Disabilities
Citation Excerpt :
Lajiness-O’Neill et al. (2006) found that subjects were relatively more impaired on perceptual-motor tasks compared to fine motor and motor-free visual–spatial tasks, suggesting that the problem is at the level of visual-motor integration. Problems with dexterity have also been reported (Roizen et al., 2010; Sobin, Monk, Kiley-Brabeck, Khuri, & Karayiorgou, 2006; Van Aken et al., 2007, 2009). To date, intellectual ability is the only variable found to be associated with motor performance in 22q11DS.
22q11.2 Deletion Syndrome (22q11DS) is a common microdeletion disorder associated with mild to moderate intellectual disability and specific neurocognitive deficits, particularly in visual-motor and attentional abilities. Currently there is evidence that the visual-motor profile of 22q11DS is not entirely mediated by intellectual disability and that these individuals have specific deficits in visual-motor integration. However, the extent to which attentional deficits, such as vigilance, influence impairments on visual motor tasks in 22q11DS is unclear. This study examines visual-motor abilities and reaction time using a range of standardised tests in 35 children with 22q11DS, 26 age-matched typically developing (TD) sibling controls and 17 low-IQ community controls. Statistically significant deficits were observed in the 22q11DS group compared to both low-IQ and TD control groups on a timed fine motor control and accuracy task. The 22q11DS group performed significantly better than the low-IQ control group on an untimed drawing task and were equivalent to the TD control group on point accuracy and simple reaction time tests. Results suggest that visual motor deficits in 22q11DS are primarily attributable to deficits in psychomotor speed which becomes apparent when tasks are timed versus untimed. Moreover, the integration of visual and motor information may be intact and, indeed, represent a relative strength in 22q11DS when there are no time constraints imposed. While this may have significant implications for cognitive remediation strategies for children with 22q11DS, the relationship between reaction time, visual reasoning, cognitive complexity, fine motor speed and accuracy, and graphomotor ability on visual-motor tasks is still unclear.

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: Supported by NIMH (MH64824 and MH65481 to W.K; 5RO1MH064824 to A.H and R.S.), HRSA-T77MC00004 (N.R.), and NHLBI (5RO1HL084410-01 to A.H and R.S.). The authors declare no conflicts of interest.

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Original Article22q11.2 Deletion Syndrome: Are Motor Deficits More Than Expected for IQ Level?

Objective

Study design

Results

Conclusions

Section snippets

Methods

Results

Discussion

J Pediatr

Lancet

Genet Med

J Pediatr

Velo-cardio-facial syndrome

Velo-cardio-facial syndrome: a distinctive behavioral phenotype

Ment Retard Dev Disabil Res Rev

Velo-cardio-facial syndrome

Curr Opin Pediatr

Disabilities and cognition in children and adolescents with 22q11 deletion syndrome

Dev Med Child Neurol

Intelligence and psychosocial adjustment in velo-cardio-facial syndrome: a study of 37 children and adolescents with VCFS

J Med Genet

Early motor development in young children with 22q11.2 deletion syndrome and a conotruncal heart defect

Dev Med Child Neurol

Original Article
22q11.2 Deletion Syndrome: Are Motor Deficits More Than Expected for IQ Level?