Chromosome 20p Partial De Novo Duplication Identified in a Female Paediatric Patient with Characteristic Facial Dysmorphism and Behavioural Anomalies

Abstract

<jats:p>Copy number variations (CNVs) involving the <jats:italic>JAG1</jats:italic> gene are rare and infrequently reported in the scientific literature. Recently, a generally healthy young patient presenting with a history of behavioural concerns was referred to us. Herein, we discuss the patient, a 7-year-old female possessing a 0.797 Mb microduplication within the short arm of chromosome 20 at band 12.2. The patient generates considerable curiosity due to the rarity of her case, which includes a <jats:italic>de novo</jats:italic> partial duplication involving the <jats:italic>JAG1</jats:italic> gene. The patient exhibits a wide range of symptoms including facial dysmorphism (dolichocephaly, round face, tented philtrum, anteverted nares, and micrognathia), clinodactyly, and an inborn congenital heart defect. She presented with behavioural concerns including ADHD-I, SPD, motor clumsiness, and poor self-regulation. Deletions in <jats:italic>JAG1</jats:italic> are often linked to <jats:italic>Alagille Syndrome</jats:italic>; however, complete duplications have not been specifically identified as disease-causing. <jats:italic>JAG1</jats:italic> mutations are reported alongside various clinical features including facial dysmorphology, heart defects, vertebral abnormalities, and ocular dysmorphic features (strabismus, epicanthal folds, and slanted palpebral fissures). This particular microduplication is rare, and thus, limited data exist regarding its significance. To our knowledge, most reported duplications are larger than 0.797 Mb. This may define a critical region causing phenotypical changes in some patient cases.</jats:p>

Short report: Twins with 20p13 duplication. Case report and comprehensive literature review

“…(2000). Commonly reported dysmorphic facial features in the setting of trisomy 20p include round face with prominent cheeks (Bartolini et al., 2013; Batanian et al., 2014; Chaabouni et al., 2007; de Ravel et al., 2003; Della‐Rosa & Vianna‐Morgante, 2000; Khattak et al., 2020; Leclercq et al., 2009; Oppenheimer et al., 2000; Pachajoa et al., 2020; Trachoo et al., 2013; Une et al., 2006; Wieczorek et al., 2003), broad nasal bridge (Bartolini et al., 2013; Della‐Rosa & Vianna‐Morgante, 2000; Oppenheimer et al., 2000; Pachajoa et al., 2020; Thomas et al., 2003; Trachoo et al., 2013), anteverted nares (Bartolini et al., 2013; Chaabouni et al., 2007; Khattak et al., 2020; Thomas et al., 2003; Une et al., 2006), short nose (Bartolini et al., 2013; Khattak et al., 2020; Leclercq et al., 2009; Trachoo et al., 2013; Wieczorek et al., 2003), micrognathia (Bartolini et al., 2013; Chaabouni et al., 2007; Choi et al., 2020; Khattak et al., 2020; Sidwell et al., 2000; Thomas et al., 2003; Venditti et al., 2003), hypertelorism (Oppenheimer et al., 2000; Une et al., 2006; Wieczorek et al., 2003), abnormal palpebral fissures (narrow, up slanted, down slanted) (Bartolini et al., 2013; Batanian et al., 2014; Chaabouni et al., 2007; Della‐Rosa & Vianna‐Morgante, 2000; Khattak et al., 2020; Oppenheimer et al., 2000; Pachajoa et al., 2020; Sidwell et al., 2000; Thomas et al., 2003; Trachoo et al., 2013; Une et al., 2006), abnormal philtrum (short, long, featureless) (Bartolini et al., …”

“…Agilent GGXChip+SNP v1.0, which features approximately 120,000 CGH probes and 60,000 SNP probes, indicated a 572.21 kb gain within chromosome band 20p13 in both twins: arr[GRCh37] 20p13(824997_1397204)x3. This 20p13 gain includes the 5′ untranslated region of FAM110A, along with the coding regions of nine additional genes: ANGPT4, RSPO4, PSMF1, SNPH, SDCBP2, FKBP1A, TMEM74B, C20orf202, RAD21L1, (Table 2), 3 long non-coding RNAs (LOC105372493, FKBP1A-SDCBP2, T A B L E 1 Clinical features of affected twins and 20 cases (Bartolini et al, 2013;Batanian et al, 2014;Chaabouni et al, 2007;Choi et al, 2020;de Ravel et al, 2003;Della-Rosa & Vianna-Morgante, 2000;DeScipio et al, 2010;Kang et al, 2012;Khattak et al, 2020;Kwon et al, 2018;Leclercq et al, 2009;Oppenheimer et al, 2000;Pachajoa et al, 2020;Sidwell et al, 2000;Thomas et al, 2003;Trachoo et al, 2013;Une et al, 2006;Venditti et al, 2003;Wieczorek et al, 2003) SDCBP2-AS1), and 1 microRNA (MIR6869). No region of monosomy was detected.…”

“…Cases of trisomy 20p occurring with no other chromosomal aberrations are uncommon (Bartolini et al, 2013;Choi et al, 2020;Sidwell et al, 2000). Trisomy 20p is most frequently the result of parental reciprocal translocation, while de novo cases rarely emerge (Bartolini et al, 2013;Chaabouni et al, 2007;Choi et al, 2020;Khattak et al, 2020;Sidwell et al, 2000). Sidwell et al (2000) advanced understanding of the phenotypes associated with this condition by describing a case of de novo pure trisomy 20p, along with 32 previously reported cases (Sidwell et al, 2000).…”

A 6.3 Mb maternally derived microduplication of 20p13p12.2 in a fetus with Brachydactyly type D and related literature review

“…JAG1 gene (OMIM#601,920) defects result in neonatal jaundice, cardiac disease, skeletal abnormalities, ocular abnormalities and Tetralogy of Fallot. A de novo 797 kb microduplication of 20p12.2 which included JAG1 was reported in a 7-year-old girl who showed a wide range of symptoms including facial dysmorphism, intellectual disability, congenital heart defect and behavioral concerns, such as ADHD (Attention Deficit Hyperactivity Disorder), SPD (Sensory Processing Dysfunction), motor clumsiness, and poor self-regulation [ 34 ]. Despite having a much smaller duplicated segment than our patients, which included only the JAG1 morbid gene and part of the non-morbid gene SLX4IP , the girl presents with more severe developmental and neurological phenotypes.…”

Additional Evidence for Neuropsychiatric Manifestations in Mosaic Trisomy 20: A Case Report and Brief Review

“…Along with numerical chromosome anomalies, such as mosaicism, structural anomalies of the chromosome 20, including ring chromosome [45], deletion of the short arm [46], microduplication within the short arm [47], and microdeleletion of the long arm [48], have also been associated with alterations in several body systems and functions as well as neurocognitive difficulties and neuropsychiatric features. Commonly reported behavioral manifestations include developmental delay, intellectual disability, sensory processing disorder, poor motor coordination, impaired speech and executive abilities, apathy or hyperactivity, loss of social skills and poor emotional regulation, obsessive behavior, psychosis, and autistic features.…”