TOO NEAR, YET TOO FAR: 22Q DELETION AND VELOCARDIOFACIAL SYNDROME MIMIC

Abstract

<h3>Introduction</h3> Chromosome 22q11.2 contains a cluster of low-copy repeats referred to as LCR22A-H. The deletion of LCR22A-D (proximal-nested) is the most common recurrent microdeletion, which leads to DiGeorge/Velocardiofacial Syndrome. In contrast, deletions in distal regions are less common but have been reported. We report a 36-year-old female with recurrent infections, ear abnormalities, facial asymmetry, and intellectual disability who was found to have deletion of LCR22D-E region. <h3>Case Description</h3> A 36-year-old female presented to our Immunodeficiency Clinic for a second opinion in the setting of recurrent infections and previous diagnosis of Velocardiofacial Syndrome. She was diagnosed with hemifacial microsomia (Goldenhar Syndrome) and ear abnormalities at birth. She was diagnosed with intellectual disability in childhood. At age 30, she developed recurrent infections. She was diagnosed with Velocardiofacial Syndrome at age 24 based on genetic testing. On review of her chromosomal microarray testing, the specific finding noted was a 1.2 mb deletion within the 22q11.21q11.22 at the distal interval, in the LCR22D-E region. <h3>Discussion</h3> Our patient had an outside diagnosis of Goldenhar Syndrome and Velocardiofacial Syndrome. Following re-review of her chromosomal microarray testing, neither of these two diagnoses were accurate. Rather, she had a deletion in the distal LCR22D-E region. Distal deletions are rarer than proximal deletions in the LCR22A-D region that lead to DiGeorge/Velocardiofacial Syndrome. Many patients with distal chromosome 22q11.2 deletions are suspicious for DiGeorge Syndrome due to phenotypic overlap. Reported features for individuals with distal deletions include abnormal ears, facial asymmetry, recurrent infections/immune deficiency, and intellectual disability, all of which our patient had.