The smallest de novo 20q11.2 microdeletion causing intellectual disability and dysmorphic features

Hanafusa, Hiroaki; Morisada, Naoya; Ishida, Yusuke; Sakata, Ryosuke; Morita, Keiichi; Miura, Shizu; Ye, Ming Juan; Yamamoto, Toshiyuki; Okamoto, Nobuhiko; Nozu, Kandai; Iijima, Kazumoto

doi:10.1038/hgv.2017.50

Cited by 4 publications

(4 citation statements)

References 30 publications

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“…A case with a 7.5 Mb 20q13.2-q13.33 deletion was reported that presented pre-and post-natal growth retardation, with absent speech, intellectual disability, hypotonia, and a unilateral cleft lip [32]. Another reported case had a de novo 20q11.2 microdeletion, measuring 1.2 Mb, which resulted in intellectual disability and dysmorphic features [33]. In our group we had a special situation, more precisely two consecutive pregnancies of the same woman, where the 20q deletion was identified, with diameters of 18.4 M and 19.5 M. In both pregnancies, microarray excluded the deletions, and two normal children were born.…”

Section: Discussionmentioning

confidence: 99%

Approach and Management of Pregnancies with Risk Identified by Non-Invasive Prenatal Testing

Gug,

Rațiu,

Andreescu

et al. 2024

JPM

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This study represents our second investigation into NIPT, involving a more extensive patient cohort with a specific emphasis on the high-risk group. The high-risk group was subsequently divided into two further groups to compare confirmed cases versus unconfirmed via direct methods. The methodology encompassed the analysis of 1400 consecutive cases from a single genetic center in western Romania, where NIPT was used to assess the risk of specific fetal chromosomal abnormalities. All high-risk cases underwent validation through direct analysis of fetal cells obtained via invasive methods, including chorionic villus sampling and amniocentesis. The confirmation process utilized QF-PCR, karyotyping, and SNP-Array methods customized to each case. Results: A high risk of aneuploidy at NIPT was identified in 36 out of 1400 (2.57%) cases and confirmed in 28 cases. The study also detected an increased risk for copy number variations (CNVs) in 1% of cases, confirmed in two instances involving one large microdeletion and one large microduplication. Trisomy 21 was the exclusive anomaly where NIPT confirmed all cases with identified risk. High-risk NIPT results which were not validated by invasive methods, were classified as false positives; parents in these cases determined to continue the pregnancy. In conclusion, NIPT can serve as a screening method for all pregnancies; however, in high-risk cases, an invasive confirmation test is strongly recommended.

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Section: Discussionmentioning

confidence: 99%

Approach and Management of Pregnancies with Risk Identified by Non-Invasive Prenatal Testing

Gug,

Rațiu,

Andreescu

et al. 2024

JPM

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“…These authors proposed the 20q11.2 microdeletion syndrome to be a new contiguous gene deletion syndrome with a recognizable phenotype; the researchers identified a 1.62 Mb minimal critical region, encompassing three genes ( GDF5 , EPB41L1 , and SAMHD1 ), as strong candidates to account for several phenotypic features. Hanafusa et al (2017) reported the smallest de novo 20q11.2 microdeletion (1.2 Mb) in 2‐year‐ and 6‐month‐old Japanese girls with intellectual disability, motor developmental delay, and facial features without feeding problems. This deletion did not overlap the minimal critical genomic region described by Jedraszak et al, encompassing the GDF5 , EPB41L1 , and SAMHD1 candidate genes.…”

Section: Discussionmentioning

confidence: 99%

Clinical and molecular cytogenetic studies of five new patients with 20q11q12 deletion and review of the literature: Proposition of two critical regions

Bensaid,

Bendahmane,

Loddo

et al. 2024

American J of Med Genetics Pt A

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Deletions of the long arm of chromosome 20 (20q) are rare, with only 16 reported patients displaying a proximal interstitial 20q deletion. A 1.62 Mb minimal critical region at 20q11.2, encompassing three genes GDF5, EPB41L1, and SAMHD1, is proposed to be responsible for this syndrome. The leading clinical features include growth retardation, intractable feeding difficulties with gastroesophageal reflux, hypotonia and psychomotor developmental delay. Common facial dysmorphisms including triangular face, hypertelorism, and hypoplastic alae nasi were additionally reported. Here, we present the clinical and molecular findings of five new patients with proximal interstitial 20q deletions. We analyzed the phenotype and molecular data of all previously reported patients with 20q11.2q12 microdeletions, along with our five new cases. Copy number variation analysis of patients in our cohort has enabled us to identify the second critical region in the 20q11.2q12 region and redefine the first region that is initially identified. The first critical region spans 359 kb at 20q11.2, containing six MIM genes, including two disease‐causing genes, GDF5 and CEP250. The second critical region spans 706 kb at 20q12, encompassing four MIM genes, including two disease‐causing genes, MAFB and TOP1. We propose GDF5 to be the primary candidate gene generating the phenotype of patients with 20q11.2 deletions. Moreover, we hypothesize TOP1 as a potential candidate gene for the second critical region at 20q12. Of note, we cannot exclude the possibility of a synergistic role of other genes involved in the deletion, including a contiguous gene deletion syndrome or position effect affecting both critical regions. Further studies focusing on patients with proximal 20q deletions are required to support our hypothesis.

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“…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.…”

Section: Discussionmentioning

confidence: 99%

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

et al. 2021

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Mosaic trisomy 20 is a genetic condition in which three chromosomes 20 are found in some cells. Its clinical phenotype seems to be highly variable, with most features not reported across all individuals and not considered pathognomonic of the condition. Limited and recent evidence indicates that neuropsychiatric manifestations may be more present in the context of trisomy 20 than was once thought. Here, we present a case of a 14-year-old female adolescent of White/Caucasian ethnicity with mosaic trisomy 20, who was admitted twice to an inpatient Child and Adolescent Neuropsychiatry Unit for persisting self-injury and suicidal ideation. A severe and complex neuropsychiatric presentation emerged at the cognitive, emotional, and behavioral levels, including mild neurodevelopmental issues, isolation, socio-relational difficulties, depressed mood, temper outbursts, irritability, low self-esteem, lack of interest, social anxiety, panic attacks, self-cutting, and low-average-range and heterogeneous intelligence quotient profile. Particularly, the patient was considered at high risk of causing harm, mainly to self, and appeared to be only partially responsive to medication, even when polypharmacy was attempted to improve clinical response. Except for school bullying, no other severe environmental risk factors were present in the patient’s history. The patient received a diagnosis of disruptive mood dysregulation disorder.

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The smallest de novo 20q11.2 microdeletion causing intellectual disability and dysmorphic features

Cited by 4 publications

References 30 publications

Approach and Management of Pregnancies with Risk Identified by Non-Invasive Prenatal Testing

Approach and Management of Pregnancies with Risk Identified by Non-Invasive Prenatal Testing

Clinical and molecular cytogenetic studies of five new patients with 20q11q12 deletion and review of the literature: Proposition of two critical regions

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

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