Variable behavioural phenotypes of patients with monosomies of 15q26 and a review of 16 cases

Poot, Martin; Stuart, A. A. Verrijn; Daalen, Emma van; Iperen, Andries van; Binsbergen, Ellen van; Hochstenbach, Ron

doi:10.1016/j.ejmg.2013.04.001

Cited by 25 publications

(27 citation statements)

References 33 publications

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“…Furthermore, there is a large spectrum of associated abnormalities, and it might be a confounding factor on clinical diagnosis [25-28]. The haploinsufficiency of the IGF1R gene has been described to be involved with developmental delay, facial and skeletal dysmorphisms, microcephaly, congenital heart disease, epilepsy, diaphragmatic hernia, renal anomalies, neonatal lymphedema, and aplasia cutis congenita [25, 26]. …”

Section: Discussionmentioning

confidence: 99%

Recurrent Copy Number Variants Associated with Syndromic Short Stature of Unknown Cause

et al. 2017

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Background/Aims: Genetic imbalances are responsible for many cases of short stature of unknown etiology. This study aims to identify recurrent pathogenic copy number variants (CNVs) in patients with syndromic short stature of unknown cause. Methods: We selected 229 children with short stature and dysmorphic features, developmental delay, and/or intellectual disability, but without a recognized syndrome. All patients were evaluated by chromosomal microarray (array-based comparative genomic hybridization/single nucleotide polymorphism array). Additionally, we searched databases and previous studies to recover recurrent pathogenic CNVs associated with short stature. Results: We identified 32 pathogenic/probably pathogenic CNVs in 229 patients. By reviewing the literature, we selected 4 previous studies which evaluated CNVs in cohorts of patients with short stature. Taken together, there were 671 patients with short stature of unknown cause evaluated by chromosomal microarray. Pathogenic/probably pathogenic CNVs were identified in 87 patients (13%). Seven recurrent CNVs, 22q11.21, 15q26, 1p36.33, Xp22.33, 17p13.3, 1q21.1, 2q24.2, were observed. They are responsible for about 40% of all pathogenic/probably pathogenic genomic imbalances found in short stature patients of unknown cause. Conclusion: CNVs seem to play a significant role in patients with short stature. Chromosomal microarray should be used as a diagnostic tool for evaluation of growth disorders, especially for syndromic short stature of unknown cause.

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Section: Discussionmentioning

confidence: 99%

Recurrent Copy Number Variants Associated with Syndromic Short Stature of Unknown Cause

et al. 2017

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“…To date, there have been 5 reports including 6 patients with 15q26 or IGFIR deletions where GH therapy was used with variable response [4,5,6,7,18,22]. The first report described a girl who was started on GH therapy mainly to prevent hypoglycaemia.…”

Section: Discussionmentioning

confidence: 99%

“…After 7.25 years of treatment, her growth response was minimal and she remained below the 3rd percentile [5]. Two other reports described a boy with ring chromosome 15 and low IGF-I levels [4] and a girl who had additional gonadotropin-releasing hormone (GnRH) analogue therapy around the time of puberty [18,22]. Change in height SDS was +1.8 after 2 years and +1.2 after 6 years of GH therapy, respectively.…”

Section: Discussionmentioning

confidence: 99%

Recombinant Human Growth Hormone Therapy in Children with Chromosome 15q26 Deletion

Ho¹,

Clayton

Vasudevan

et al. 2015

Horm Res Paediatr

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Background: The insulin-like growth factor 1 receptor (IGF IR) gene is located on chromosome 15q26.3. Heterozygous 15q26 deletions involving the IGFIR gene are rare, resulting in intrauterine and postnatal growth retardation, developmental delay and microcephaly. Limited evidence exists on the effect of growth hormone (GH) therapy in these cases. Methods: We report a series of cases with 15q26 deletions, including response to GH treatment. Results: Seven children (2 males) presented with short stature [median height standard deviation score (SDS) of -4.8 (range -3.0 to -5.6)]. GH was started at a median age of 5 years (range 1.8 to 12.4) for a median duration of 5.8 years (range 1.0 to 12.4). Median height SDS increased by +0.6 (range 0.1 to 1.0), +1.3 (range 0.1 to 2.4) and +1.4 (range 0.8 to 3.3) after 1 (n = 7), 5 (n = 4) and 10 years (n = 3) of GH treatment, respectively. Four patients reached final height after 5.8 to 12.4 years of GH with a median change in height SDS of +1.1 (range 0 to 3.3). Conclusion: This study demonstrates a moderate, though variable, response to GH therapy, suggesting that GH resistance caused by heterozygous IGFIR deletions can be partially overcome by GH therapy. The first-year response was moderate, and whilst long-term treatment improved height SDS, the final adult height remained reduced. Therefore, an individual trial of GH therapy may be appropriate in these patients.

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“…Some patients with deletions in region 15q26.3 initially showed an isolated form of ISS, but later developed behavioral problems. These later developments may indicate a 'hidden' second locus or gene, yet should not bar us from considering treatment options that are supported by a known CNV or gene mutation [Poot et al, 2013]. If a deletion of or an inactivating mutation in the IGF1R gene is discovered, ISS may become a disorder amenable to growth hormone treatment [Poot et al, 2013].…”

Section: All Humans Great or Small Short Or Tallmentioning

confidence: 99%

“…been found in patients with intellectual delay (ID), which led investigators to invoke a polygenic model to explain phenotypic heterogeneity among patients with ID and also for patients with ISS and a deletion in region 15q26 [Girirajan and Eichler, 2010;Poot et al, 2011Poot et al, , 2013Girirajan et al, 2012]. For 24 of the 33 patients with one or more novel potentially pathogenic CNVs, segregation analysis could be performed.…”

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confidence: 99%

All Humans, Great or Small, Short or Tall

Poot¹

2014

Mol Syndromol

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Variable behavioural phenotypes of patients with monosomies of 15q26 and a review of 16 cases

Cited by 25 publications

References 33 publications

Recurrent Copy Number Variants Associated with Syndromic Short Stature of Unknown Cause

Recurrent Copy Number Variants Associated with Syndromic Short Stature of Unknown Cause

Recombinant Human Growth Hormone Therapy in Children with Chromosome 15q26 Deletion

All Humans, Great or Small, Short or Tall

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