Cognitive Deficit, Learning Difficulties, Severe Behavioral Abnormalities and Healed Cleft Lip in a Patient with a 1.2-Mb Distal Microduplication at 22q11.2

Abstract

The 22q11.2 duplication syndrome has been recently characterized as a new entity with features overlapping the 22q11.2 deletion syndrome. Most 22q11.2 duplications represent reciprocal events of the typical 3-Mb deletions extending between low copy repeat (LCR) 22-A and LCR22-D. It has been suggested that the clinical manifestations observed in patients with 22q11.2 microduplications may range from milder phenotypes to multiple severe defects, and this variability could be responsible for many undetected cases. Here, we report on a patient with a 1.2-Mb microduplication at 22q11.2 spanning LCR22-F and LCR22-H which harbor the SMARCB1 and SNRPD3 genes. The patient presented healed cleft lip, mild facial dysmorphism, cognitive deficit, and delayed language development associated with severe behavioral problems including learning difficulties and aggressive behavior.

Clinical correlates in children with autism spectrum disorder and CNVs: Systematic investigation in a clinical setting

“…In the present patient, 12q21.2q21.31 deletion encompassed LIN7A gene encoding a scaffold protein important for synapse functions and neuronal migration during corticogenesis supporting a role in the pathomechanism of ID and ASD (Matsumoto et al, 2014). Patients with 22q11.23 duplication as observed in our proband 5 may show extremely diverse features that range from normal to multiple remarkable defects, including cognitive impairment, learning disability and developmental delay (Ribeiro‐Bicudo, Campos, Gamba, Candido Sandri, & Richieri‐Costa, 2013).…”

22q11.2 Microduplication: An Enigmatic Genetic Disorder

“…[16][17][18][19][20][21] There are reports of variable cognitive deficits, which are generally mild. 1,2,6,8,9,22 This case illustrates the considerable challenges in interpreting copy number variations. A review of the phenotype of microduplications involving similar LCRs did not establish any clear genotype correlation.…”

Behavioral abnormalities are common and severe in patients with distal 22q11.2 microdeletions and microduplications

“…(2013) with an inherited LCR F–H duplication. His behavior was described as ranging from apathy to extreme anxiety with immaturity and dependence on his mother for any decision.…”

“…Behavior abnormalities have been highlighted in the reports of some patients with distal 22q11.2, such as the case of Ribeiro-Bicudo et al (2013) with an inherited LCR F-H duplication. His behavior was described as ranging from apathy to extreme anxiety with immaturity and dependence on his mother for any decision.…”