15q26 Deletion in a Patient with Congenital Heart Defect, Growth Restriction and Intellectual Disability: Case Report and Literature Review

Overview

Journal Ital J Pediatr

Publisher Biomed Central

Specialty Pediatrics

Date 2021 Sep 17

PMID 34530895

Citations 7

Authors

Yahya Benbouchta

Nicole de Leeuw

Saadia Amasdl

Aziza Sbiti

Dominique Smeets

Khalid Sadki

Abdelaziz Sefiani

Affiliations

Soon will be listed here.

Abstract

Background: 15q26 deletion is a relatively rare chromosomal disorder, and it is described only in few cases. Patients with this aberration show many signs and symptoms, particularly pre- and postnatal growth restriction, developmental delay, microcephaly, intellectual disability and various congenital malformations.

Case Presentation: We report on a girl, 4 years old, of consanguineous parents, with a 15q26 deletion. Clinical manifestations included failure to thrive, developmental delay, microcephaly, dysmorphic facies with broad forehead, hypertelorism, narrowed eyelid slits and protruding columella. The patient also showed skeletal abnormalities, especially clinodactyly of the 5th finger, varus equine right foot and left club foot. Additionally, she had teething delay and divergent strabismus. Heart ultrasound displayed two atrial septal defects with left-to-right shunt, enlarging the right cavities. Routine cytogenetic analysis revealed a shortened 15q chromosome. Subsequent array analysis disclosed a terminal 9.15 Mb deletion at subband 15q26.1-q26.3. Four candidate genes associated with 15q26 deletion phenotype were within the deleted region, i.e. IGF1R, NR2F2, CHD2 and MEF2A.

Conclusion: We report on an additional case of 15q26 monosomy, characterized by array-CGH. Molecular cytogenetic analysis allowed us to identify the exact size of the deletion, and four candidate genes for genotype-phenotype correlation. 15q26 monosomy should be considered when growth retardation is associated with hearing anomalies and congenital heart defect, especially atrioventricular septal defects (AVSDs) and/or aortic arch anomaly (AAA).

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References

Choi J, Kang M, Kim G, Hong M, Jin H, Lee B . Clinical and functional characteristics of a novel heterozygous mutation of the IGF1R gene and IGF1R haploinsufficiency due to terminal 15q26.2->qter deletion in patients with intrauterine growth retardation and postnatal catch-up growth failure. J Clin Endocrinol Metab. 2010; 96(1):E130-4. DOI: 10.1210/jc.2010-1789. View

Lopez I, Bafalliu J, Bernabe M, Garcia F, Costa M, Guillen-Navarro E . Prenatal diagnosis of de novo deletions of 8p23.1 or 15q26.1 in two fetuses with diaphragmatic hernia and congenital heart defects. Prenat Diagn. 2006; 26(6):577-80. DOI: 10.1002/pd.1468. View

Capelli L, Krepischi A, Gurgel-Giannetti J, Mendes M, Rodrigues T, Varela M . Deletion of the RMGA and CHD2 genes in a child with epilepsy and mental deficiency. Eur J Med Genet. 2011; 55(2):132-4. DOI: 10.1016/j.ejmg.2011.10.004. View

Forbes B, Blyth A, Wit J . Disorders of IGFs and IGF-1R signaling pathways. Mol Cell Endocrinol. 2020; 518:111035. DOI: 10.1016/j.mce.2020.111035. View

Abuzzahab M, Schneider A, Goddard A, Grigorescu F, Lautier C, Keller E . IGF-I receptor mutations resulting in intrauterine and postnatal growth retardation. N Engl J Med. 2003; 349(23):2211-22. DOI: 10.1056/NEJMoa010107. View

Bhagavatula M, Fan C, Shen G, Cassano J, Plow E, Topol E . Transcription factor MEF2A mutations in patients with coronary artery disease. Hum Mol Genet. 2004; 13(24):3181-8. PMC: 1579761. DOI: 10.1093/hmg/ddh329. View

Tonnies H, Schulze I, Hennies H, Neumann L, Keitzer R, Neitzel H . De novo terminal deletion of chromosome 15q26.1 characterised by comparative genomic hybridisation and FISH with locus specific probes. J Med Genet. 2001; 38(9):617-21. PMC: 1734945. DOI: 10.1136/jmg.38.9.617. View

Lurie I . Kidney abnormalities in persons with monosomy 15q26. Am J Med Genet A. 2008; 146A(13):1761-4. DOI: 10.1002/ajmg.a.32333. View

Ho S, Clayton P, Vasudevan P, Greening J, Wardhaugh B, Shaw N . Recombinant Human Growth Hormone Therapy in Children with Chromosome 15q26 Deletion. Horm Res Paediatr. 2015; . DOI: 10.1159/000380949. View

10.

Klaassens M, van Dooren M, Eussen H, Douben H, den Dekker A, Lee C . Congenital diaphragmatic hernia and chromosome 15q26: determination of a candidate region by use of fluorescent in situ hybridization and array-based comparative genomic hybridization. Am J Hum Genet. 2005; 76(5):877-82. PMC: 1199376. DOI: 10.1086/429842. View

11.

Biggio Jr J, Descartes M, Carroll A, Holt R . Congenital diaphragmatic hernia: is 15q26.1-26.2 a candidate locus?. Am J Med Genet A. 2004; 126A(2):183-5. DOI: 10.1002/ajmg.a.20464. View

12.

Poot M, Eleveld M, van t Slot R, van Genderen M, Verrijn Stuart A, Hochstenbach R . Proportional growth failure and oculocutaneous albinism in a girl with a 6.87 Mb deletion of region 15q26.2-->qter. Eur J Med Genet. 2007; 50(6):432-40. DOI: 10.1016/j.ejmg.2007.08.003. View

13.

Chenier S, Yoon G, Argiropoulos B, Lauzon J, Laframboise R, Ahn J . CHD2 haploinsufficiency is associated with developmental delay, intellectual disability, epilepsy and neurobehavioural problems. J Neurodev Disord. 2014; 6(1):9. PMC: 4022362. DOI: 10.1186/1866-1955-6-9. View

14.

Baker J, Liu J, Robertson E, Efstratiadis A . Role of insulin-like growth factors in embryonic and postnatal growth. Cell. 1993; 75(1):73-82. View

15.

ORiordan A, McGrath N, Sharif F, Murphy N, Franklin O, Lynch S . Expanding the clinical spectrum of chromosome 15q26 terminal deletions associated with IGF-1 resistance. Eur J Pediatr. 2016; 176(1):137-142. DOI: 10.1007/s00431-016-2802-y. View

16.

Rump P, Dijkhuizen T, Sikkema-Raddatz B, Lemmink H, Vos Y, Verheij J . Drayer's syndrome of mental retardation, microcephaly, short stature and absent phalanges is caused by a recurrent deletion of chromosome 15(q26.2-->qter). Clin Genet. 2008; 74(5):455-62. DOI: 10.1111/j.1399-0004.2008.01064.x. View

17.

Nakamura E, Makita Y, Okamoto T, Nagaya K, Hayashi T, Sugimoto M . 5.78 Mb terminal deletion of chromosome 15q in a girl, evaluation of NR2F2 as candidate gene for congenital heart defects. Eur J Med Genet. 2010; 54(3):354-6. DOI: 10.1016/j.ejmg.2010.12.004. View

18.

Bhakta K, Marlin S, Shen J, Fernandes C . Terminal deletion of chromosome 15q26.1: case report and brief literature review. J Perinatol. 2005; 25(6):429-32. DOI: 10.1038/sj.jp.7211301. View

19.

Dateki S, Fukami M, Tanaka Y, Sasaki G, Moriuchi H, Ogata T . Identification of chromosome 15q26 terminal deletion with telomere sequences and its bearing on genotype-phenotype analysis. Endocr J. 2011; 58(3):155-9. DOI: 10.1507/endocrj.k10e-251. View

20.

Poot M, Verrijn Stuart A, van Daalen E, van Iperen A, van Binsbergen E, Hochstenbach R . Variable behavioural phenotypes of patients with monosomies of 15q26 and a review of 16 cases. Eur J Med Genet. 2013; 56(7):346-50. DOI: 10.1016/j.ejmg.2013.04.001. View