Abstract
Background: The importance of copy number variants
(CNV) in complex pediatric disorders is of growing interest. 22q11
deletion syndrome (22q11DS) is a CNV disorder that has a diverse
clinical presentation including congenital heart defects, palatal
abnormality, immunodeficiency, hypocalcaemia, language and learning
disabilities, and psychiatric disorders. Many patients with 22q11DS
present with signs of Autism Spectrum Disorders (ASD), which
manifest as impairments in social interaction and communication,
repetitive behaviors, and idiosyncratic interests. The
physiological mechanisms that link 22qDS with ASD are unknown. This
study explores the influence of hypocalcaemia in 22q11DS on the
risk and severity of social communication delays, which can be
associated with ASD.
Methods: In a retrospective cohort study testing the
association of physiological variables with social and
communication abilities in infants and toddlers from Children's
Healthcare of Atlanta 22q11 clinic, we abstracted medical and
laboratory records for the earliest and lowest serum
albumin-adjusted calcium level (n=151). Multiple childhood
psychological assessments were used to detect the presence of ASD
symptoms. The models controlled for age at assessment, age at
calcium draw, and gender.
Results and Discussion: On average, the calcium level
was taken contemporaneously with CSBS. There was a significant
relationship between the lowest calcium value and CSBS Social Score
(R
2=0.25, p=0.05), CSBS Speech Score
(R
2=0.32, p=0.04), CSBS Symbolic Score
(R
2=0.31, p=0.02), and overall CSBS Total Score
(R
2=0.28, p=0.04). This relationship between low calcium
and deficits in CSBS was also seen at the trend level in models
using the earliest calcium value (p=0.08-p=0.11). Earliest calcium
value was significantly associated with CDIP social scores
(p=0.05). Finally, there appears to be a significant association
between hypocalcaemia and the level of infant hypoxia
(p=0.007).
Conclusions: Lower calcium level associates with
impaired social communication development in patients with 22q11DS.
Further studies are needed to elucidate the relationship between
hypoxia and hypocalcaemia.Early peripheral risk factors such as
hypocalcaemia may impact neuropsychological outcomes in 22q11DS
patients. Calcium dysregulation affects neuroplasticity, and
studies are needed to explore the influence of hypocalcaemia, and
the role of calcium management, on early and later
neurodevelopmental and psychiatric outcomes.
Table of Contents
TABLE OF
CONTENTS
INTRODUCTION - 1
BACKGROUND/ LITERATURE REVIEW -
3
METHODS - 9
RESULTS - 21
DISCUSSION - 30
FIGURES - 34
TABLES - 38
APPENDIX - 55
REFERENCES -83
About this Master's Thesis
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