A De Novo Xp11.23 Duplication in a Girl with a Severe Phenotype: Expanding the Clinical Spectrum

Abstract

The Xp11.22-p11.23 duplication syndrome was described in 2009 by Giorda et al and is characterized by intellectual disability, speech delay, and electroencephalography anomalies. We report a case of a 23-month-old girl who presented with epilepsy and global developmental delay and who had a small duplication at Xp11.23. The case we present here is the first case showing the clinical features of Xp11.22-p11.23 duplication syndrome only involving synovial sarcoma, X breakpoint ( ) genes: , , , and . This case report contributes to an expanding clinical spectrum of Xp11.22-p11.23 duplication syndrome.

Xp11.2 Duplication in Females: Unique Features of a Rare Copy Number Variation

“…Our most noteworthy observation on Patient 1 refers to her OFC (below the 3rd percentile). As far as we know, only two girls has been reported to date with OFC < 3rd percentile (Patient 2 at Edens et al, 2011;Arican et al, 2018). In addition, the mother of Giorda's Patient 1 should be mentioned with the same OFC value.…”

“…Non-recurrent duplications of 0, 3-55 Mb in size have been reported in addition to the recurrent form of about 4.5 Mb, therefore the genes involved in the individual patient's duplications may be quite different. Patients with this copy number alteration, which have become known so far, show surprisingly similar symptoms despite the variability in CNV size: the resulting symptoms do not correlate with size and gene content of the affected genomic regions (Giorda et al, 2009;Zou and Milunsky, 2009;Flynn et al, 2011;Arican et al, 2018).…”

“…The duplication affecting the Xp11.23p11.22 region is unique even among these specific CNVs of X chromosome. It is very rare occurring in both genders (Kokalj Vokac et al, 2002;Bonnet et al, 2006;Froyen et al, 2008Froyen et al, , 2012Monnot et al, 2008;Giorda et al, 2009;Zou and Milunsky, 2009;Holden et al, 2010;Honda et al, 2010;Broli et al, 2011;Chung et al, 2011;Edens et al, 2011;El-Hattab et al, 2011;Flynn et al, 2011;Nizon et al, 2014;Evers et al, 2015;Grams et al, 2015;Moey et al, 2016;Orivoli et al, 2016;Arican et al, 2018;Wang et al, 2020). Inherited and de novo forms are known, all de novo Xp11.23 duplications in which parent of origin has been determined have been paternally inherited (Deng et al, 1990).…”

Pure De Novo 4.5 Mb Duplication at Xp11.22-p11.23 in an 18-Month-Old Boy: Phenotypic and Molecular Characterization

“…Duplicated synaptophysin (SYP) codes a protein of the synaptic vesicle membrane and mutations have been associated with ID and epilepsy (10). Pinar et al in 2018 (11) reported a small duplication of only SSX1, SSX9, SXX3 and SXX4 at Xp11.23 in a 23-month-old girl with epilepsy and global developmental delay. The patient had very severe ID and died at 25 months of age from severe pneumonia.…”

Chromosomal Microarray Analysis in Children with Unexplained Developmental Delay/Intellectual Disability

“…CMA for discovery of copy number variants (CNVs) is now recommended as a first-line diagnostic tool in patients with unexplained DD/ID and ASD. 4,5 CMA provides a high-resolution genome-wide scan of genomic CNVs such as microdeletions and microduplications. The ability of generating high-resolution genomic data also leads to difficulties in determining CNVs' clinical significance.…”