Two patients with chromosome 22q11.2 deletion presenting with childhood obesity and hyperphagia

Bassett, John; Chandler, Katherine; Douzgou, Sofia

doi:10.1016/j.ejmg.2016.05.008

Cited by 5 publications

(3 citation statements)

References 9 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…As these CNVs arise in more than 2 unrelated individuals, we implicate them as novel loci with a potential role in obesity susceptibility. A link between the 22q11.2 region with obesity is also supported by previous works showing that 22q11.2DS deletion carriers have increased rates of obesity [ 55 – 57 ], as well as reports of patients presenting childhood obesity with hyperphagia [ 58 , 59 ]. Overweight and obesity (with or without hyperphagia) have also been described in a number of patients with distal 22q11.2 deletions [ 60 – 63 ].…”

Section: Discussionsupporting

confidence: 59%

Chromosomal microarray analysis in the genetic evaluation of 279 patients with syndromic obesity

et al. 2018

View full text Add to dashboard Cite

BackgroundSyndromic obesity is an umbrella term used to describe cases where obesity occurs with additional phenotypes. It often arises as part of a distinct genetic syndrome with Prader-Willi syndrome being a classical example. These rare forms of obesity provide a unique source for identifying obesity-related genetic changes. Chromosomal microarray analysis (CMA) has allowed the characterization of new genetic forms of syndromic obesity, which are due to copy number variants (CNVs); however, CMA in large cohorts requires more study. The aim of this study was to characterize the CNVs detected by CMA in 279 patients with a syndromic obesity phenotype.ResultsPathogenic CNVs were detected in 61 patients (22%) and, among them, 35 had overlapping/recurrent CNVs. Genomic imbalance disorders known to cause syndromic obesity were found in 8.2% of cases, most commonly deletions of 1p36, 2q37 and 17p11.2 (5.4%), and we also detected deletions at 1p21.3, 2p25.3, 6q16, 9q34, 16p11.2 distal and proximal, as well as an unbalanced translocation resulting in duplication of the GNB3 gene responsible for a syndromic for of childhood obesity. Deletions of 9p terminal and 22q11.2 proximal/distal were found in 1% and 3% of cases, respectively. They thus emerge as being new putative obesity-susceptibility loci. We found additional CNVs in our study that overlapped with CNVs previously reported in cases of syndromic obesity, including a new case of 13q34 deletion (CHAMP1), bringing to 7 the number of patients in whom such defects have been described in association with obesity. Our findings implicate many genes previously associated with obesity (e.g. PTBP2, TMEM18, MYT1L, POU3F2, SIM1, SH2B1), and also identified other potentially relevant candidates including TAS1R3, ALOX5AP, and GAS6.ConclusionUnderstanding the genetics of obesity has proven difficult, and considerable insight has been obtained from the study of genomic disorders with obesity associated as part of the phenotype. In our study, CNVs known to be causal for syndromic obesity were detected in 8.2% of patients, but we provide evidence for a genetic basis of obesity in as many as 14% of cases. Overall, our results underscore the genetic heterogeneity in syndromic forms of obesity, which imposes a substantial challenge for diagnosis.Electronic supplementary materialThe online version of this article (10.1186/s13039-018-0363-7) contains supplementary material, which is available to authorized users.

show abstract

Section: Discussionsupporting

confidence: 59%

Chromosomal microarray analysis in the genetic evaluation of 279 patients with syndromic obesity

et al. 2018

View full text Add to dashboard Cite

show abstract

“…Obesity is resulted from bulimia. Obsessive behaviors secondary to some of the psychiatric features is commonly seen in 22q11.2DS that are similar to Prader-Willi Syndrome (PWS) [20]. Therefore, 22q11.2DS should be managed similarly to PWS.…”

Section: Discussionmentioning

confidence: 99%

A case of follow-up of a patient with 22q11.2 distal deletion syndrome and a review of the literature

Park

Jang

et al. 2021

J Genet Med

View full text Add to dashboard Cite

Microdeletions of chromosome 22q11.2 are one of the most common microdeletions occurring in humans, and is known to be associated with a wide range of highly variable features. These deletions occur within a cluster of low copy repeats (LCRs) in 22q11.2, referred to as LCR22 A-H. DiGeorge (DGS)/velocardiofacial syndrome is the most prevalent form of a 22q11.2 deletions, caused by mainly proximal deletions between LCR22 A and D. As deletions of distal portion to the DGS deleted regions has been extensively studied, the recurrent distal 22q11.2 microdeletions distinct from DGS has been suggested as several clinical entities according to the various in size and position of the deletions on LCRs. We report a case of long-term follow-up of a female diagnosed with a 22q11.2 distal deletion syndrome, identified a deletion of 1.9 Mb at 22q11.21q11.23 (chr22: 21,798,906-23,653,963) using single nucleotide polymorphism array. This region was categorized as distal deletion type of 22q11.2, involving LCR22 D-F. She was born as a preterm, low birth weight to healthy non-consanguineous Korean parents. She showed developmental delay, growth retardation, dysmorphic facial features, and mild skeletal deformities. The patient underwent a growth hormone administration due to growth impairment without catch-up growth. While a height gain was noted, she had become overweight and was subsequently diagnosed with pre-diabetes. Our case could help broaden the genetic and clinical spectrum of 22q11.2 distal deletions.

show abstract

“…The 2pter region is also of interest, containing the myelin transcription factor 1 like (MYT1L) gene, which has been implicated in intellectual disability and obesity (8). Deletions in the 15qter region, distally from the PWS region, have also been described, as have deletions in the 22q11.2 region (9), or alterations of the X chromosome, such as Xq duplications (10) or even fragile X syndrome (11). There can also be small genetic defects in the PWS critical region which do not qualify as a molecular diagnosis of PWS, but may produce a PWS phenotype.…”

Section: Essential Pointsmentioning

confidence: 99%

The Spectrum of the Prader–Willi-like Pheno- and Genotype: A Review of the Literature

2021

View full text Add to dashboard Cite

Prader-Willi syndrome (PWS) is a rare genetic syndrome, caused by the loss of expression of the paternal chromosome 15q11-q13 region. Over the past years, many cases of patients with characteristics similar to PWS, but without a typical genetic aberration of the 15q11-q13 region, have been described. These patients are often labelled as Prader-Willi-like (PWL). PWL is an as-yet poorly defined syndrome, potentially affecting a significant number of children and adults. In the current clinical practice, patients labelled as PWL are mostly left without treatment options. Considering the similarities with PWS, children with PWL might benefit from the same care and treatment as children with PWS. This review gives more insight into the pheno- and genotype of PWL and includes 86 papers, containing 368 cases of patients with a PWL phenotype. We describe mutations and aberrations for consideration when suspicion of PWS remains after negative testing. The most common genetic diagnoses were Temple syndrome (formerly known as maternal uniparental disomy 14), Schaaf-Yang syndrome (truncating mutation in the MAGEL2 gene), 1p36 deletion, 2p deletion, 6q deletion, 6q duplication, 15q deletion,15q duplication, 19p deletion, fragile X syndrome and Xq duplication. We found that the most prevalent symptoms in the entire group were developmental delay/intellectual disability (76%), speech problems (64%), overweight/obesity (57%), hypotonia (56%) and psycho-behavioral problems (53%).In addition, we propose a diagnostic approach to patients with a PWL phenotype for (pediatric) endocrinologists. PWL comprises a complex and diverse group of patients, which calls for multidisciplinary care with an individualized approach.

show abstract

Two patients with chromosome 22q11.2 deletion presenting with childhood obesity and hyperphagia

Cited by 5 publications

References 9 publications

Chromosomal microarray analysis in the genetic evaluation of 279 patients with syndromic obesity

Chromosomal microarray analysis in the genetic evaluation of 279 patients with syndromic obesity

A case of follow-up of a patient with 22q11.2 distal deletion syndrome and a review of the literature

The Spectrum of the Prader–Willi-like Pheno- and Genotype: A Review of the Literature

Contact Info

Product

Resources

About