A Boy with an LCR3/4-Flanked 10q22.3q23.2 Microdeletion and Uncommon Phenotypic Features

Abstract

The recurrent 10q22.3q23.2 deletion with breakpoints within low copy repeats 3 and 4 is a rare genomic disorder, reported in only 13 patients to date. The phenotype is rather uncharacteristic, which makes a clinical diagnosis difficult. A phenotypic feature described in almost all patients is a delay in speech development, albeit systematic studies are still pending. In this study, we report on a boy with an LCR3/4-flanked 10q22.3q23.2 deletion exhibiting an age-appropriate language development evaluated by a standardized test at an age of 2 years and 3 months. The boy was born with a cleft palate - a feature not present in any of the patients described before. Previously reported cases are reviewed, and the role of the BMPR1A gene is discussed. The phenotype of patients with an LCR3/4-flanked 10q22.3q23.2 deletion can be rather variable, so counseling the families regarding the prognosis of an affected child should be done with caution. Long-term studies of affected children are needed to delineate the natural history of this rare disorder.

De Novo 1.77-Mb Microdeletion of 10q22.2q22.3 in a Girl with Developmental Delay, Speech Delay, Congenital Cleft Palate, and Bilateral Hearing Impairment

“…Screenshot from the UCSC Genome Browser showing the positions of the deletions of patients previously reported (Balciuniene et al, 2007; Alliman et al, 2010; Tzschach et al, 2010; Reddy et al, 2011; Singh et al, 2011; van Bon et al, 2011; Petrova et al, 2014) and the position of the 10q22.2q22.3 deletion (our case).…”

“…The recurrent 10q22.3q23.2 deletion with breakpoints within low copy repeats 3 and 4 is a rare genomic disorder that has been reported in only 15 patients to date (Balciuniene et al, 2007; Alliman et al, 2010; van Bon et al, 2011; Reddy et al, 2011; Singh et al, 2011; Petrova et al, 2014) (Table 2). The phenotype is uncharacteristic, which complicates a clinical diagnosis.…”

A New Case of the Rare 10q22.3q23.2 Microdeletion Flanked by Low-Copy Repeats 3/4

“…PTEN has a recognized tumor suppressor role [Li et al, 1997] and is associated with Cowden syndrome and Bannayan-RileyRuvalcaba syndrome, suggesting that contiguous deletion of both BMPR1A and PTEN is required for polyposis development [Zhou et al, 2003;Dahdaleh et al, 2012]. PTEN is not present in LCR 3/4-flanked 10q22.3q23.2 deletion and none of the patients with similar deletions were reported to have juvenile polyposis of infancy or to have developed the polyposis phenotype [Petrova et al, 2014].…”

“…Nevertheless, only 14 novel deletions and 7 duplications with breakpoints within LCRs 3/4 have been described [Goss et al, 1998;Han et al, 2004;Dufke et al, 2006;Balciuniene et al, 2007;Erdogan et al, 2008;Alliman et al, 2010;Reddy et al, 2011;Singh et al, 2011;van Bon et al, 2011;Petrova et al, 2014].…”

Two de novo Overlapping Interstitial Duplications at 10q22 Associated with Speech Impairments, Behaviour Problems, Genital Anomalies, Developmental Delay and Intellectual Disability

“…Recurrent deletions at 10q22.3q23.3 mediated by LCR3-4 are associated with intellectual disability, developmental delay, dysmorphic features, behavior problems and other neurodevelopmental disorders, whereas reciprocal duplications are contributed to distinctive facial features, cognitive impairments, congenital heart disease, and delays in language and motor development. Interstitial deletions or duplications at 10q22.3q23.3 are infrequently reported, and a distinct clinically recognizable syndrome has not emerged [2][3][4][5][6][7][8][9][10].…”