15q11.2 Deletion Syndrome: Expanding the Phenotype

15q11.2 Deletion Syndrome: Expanding the Phenotype

Luis F. Escobar1*, Rebecca Carr1, 2, Lauren Bogue1

1Medical Genetics and Neurodevelopmental Center.
2Peyton Manning Children’s Hospital at St. Vincent, Indianapolis, In 46260.  Purdue University, Lafayette, In 47907.

International-Journal-of-Case-Reports-2d code

Background: Although multiple reports exist in the literature of patients with 15q11.2 deletion syndrome, the variability of the phenotype has made clinical delineation difficult. Neuro-developmental scores have not been previously reported. We present clinical findings in a group of 16 patients referred to our center for evaluation and management of neurodevelopmental difficulties.

Methods: All patients were seen in our center between 2005 and 2016. They were seen by a clinical geneticist and their diagnosis of 15q11.2 deletion syndrome was confirmed by a microarray analysis. Bayley Scales of Infant Development was done and provided a mental developmental index and a motor developmental index. The data collected was then compared to previous reports in the literature of patients with 15q11.2 deletion syndrome.

Results: The reviewed group consisted of 10 males and 6 female patients between the ages of 3 and 15 years. The most common clinical findings included developmental delay (94%),  hypotonia (88%), ADHD (75%), anxiety (50%), feeding difficulties (44%), autism (31%), dolichocephaly (25%), 2-3 toe syndactyly (19%), seizure activity (19%), and congenital heart disease (13%).  Additional findings included prominence of the metopic suture, epicanthal folds, micrognathia, ankle torsion, incontinence, and sleeping difficulties.  Our developmental evaluation by the Bayley Scales of Infant Development indicated an average Mental Developmental Index of 75 (NL = >85) and Motor Developmental Index of 75 (NL = >85) in the patients less than 3 years old.  Close to 43% of patients had an occipitofrontal circumference (OFC) greater than or equal to the 97th.

Conclusion: The data provided here intends to expand the phenotype of the 15q11.2 deletion syndrome.  Neurodevelopmental scores have not been previously reported in 15q11.2 del syndrome which were found to be in the mild developmental delay range.

Keywords: 15q11.2, deletion, phenotype

Free Full-text PDF

How to cite this article:

Luis F. Escobar, Rebecca Carr, Lauren Bogue. 15q11.2 Deletion Syndrome: Expanding the Phenotype. International Journal of Case Reports, 2020; 4:163.. DOI: 10.28933/ijcr-2020-09-1105


1. Murthy SK, Nygren AO, El Shakankiry HM, Schouten JP, Al Khayat AI, Ridha A, Al Ali MT. 2007. Detection of a novel familial deletion of four genes between BP1 and BP2 of the Prader-Willi/angelman syndrome critical region by oligo-array CGH in a child with neurological disorder and speech impairment. Cytogenet Genome Res 116:135–140.
2. Doornbos M, Sikkema-Raddatz B, Ruijvenkamp CA, Dijkhuizen T, Bijlsma EK, Gijsbers AC, Hilhorst-Hofstee Y, Hordijk R, Verbruggen KT, Kerstjens-Frederikse WS, van Essen T, Kok K, van Silfhout AT, Breuning M, van Ravenswaaij-Arts CM. 2009. Nine patients with a microdeletion 15q11.2 between breakpoints 1 and 2 of the Prader-Willi critical region, possibly associated with behavioural disturbances. Eur J Med Genet 52:108–115.
3. von der Lippe C, Rustad C, Heimdal K, Rodningen OK. 2011. 15q11.2 microdeletion—Sev- en new patients with delayed development and/or behavioral problems. Eur J Med Genet 54:357–360.
4. De Kovel, C.G.; Trucks, H.; Helbig, I.; Mefford, H.C.; Baker, C.; Leu, C.; Kluck, C.; Muhle, H.; von Spiczak, S.; Ostertag, P.; et al. Recurrent microdeletion at 15q11.2 and 16p13.11 predispose to idiopathic generalized epi-lepsies. Brain 2010, 133, 23–32.
5. Stefansson, H.; Rujescu, D.; Cichon, S.; Pietilainen, O.P.; Ingason, A.; Steinberg, S.; Fossdal, R.; Sigurdsson, E.; Sigmundsson, T.; Buizer-Voskamp, J.E.; et al. Large recurrent microdeletions associated with schizophrenia. Nature 2008, 455, 232–236.
6. Rees, E.; Walters, J.T.R.; Georgieva, L.; Isles, A.R.; Chambert, K.D.; Richards, A.L.; Ma-honey-Davies, G.; Legge, S.E.; Moran, J.L.; McCarroll, S.A.; et al. Analysis of copy number variations at 15 schizophrenia-associated loci. Br. J. Psychiatry 2014, 204, 108–114.
7. Chaste, P.; Sanders, S.J.; Mohan, K.N.; Klei, L.; Song, Y.; Murtha, M.T.; Hus, V.; Lowe, J.K.; Willsey, A.J.; Moreno-De-Luca, D.; et al. Modest impact on risk for Autism Spectrum Disorder of rare copy number variants at 15q11.2, specifically breakpoints 1 to 2. Autism Res. 2014, 7, 355–362.
8. Cafferkey, M.; Ahn, J.W.; Flinter, F.; Ogilvie, C. Phenotypic features in patients with 15q11.2 (BP1–BP2) deletion: Further delineation of an emerging syndrome. Am. J. Med. Genet. Part A 2014, 164A, 1916–1922
9. Cox DM, Butler MG. The 15q11.2 BP1–BP2 Microdeletion Syndrome: A Review. Borlongan C, ed. International Journal of Molecular Sciences. 2015;16(2):4068-4082. doi:10.3390/ijms16024068
10. Rosenfeld, J.A.; Coe, B.P.; Eichler, E.E.; Cuckle, H.; Shaffer, L.G. Estimates of penetrance for recurrent pathogenic copy-number variants. Genet Med. 2013, 15, 478–481.
11. Cook EH, Jr., Lindgren V, Leventhal BL, Courchesne R, Lincoln A, Shulman C, Lord C, Courchesne E. 1997. Autism or atypical autism in maternally but not paternally derived proximal 15q duplication. Am J Hum Genet 60:928–934.
12. Repetto GM, White LM, Bader PJ, Johnson D, Knoll JH. 1998. Interstitial duplications of chromosome region 15q11q13: Clinical and molecular characterization. Am J Med Genet 79:82–89.
13. Butler, M.G.; Bittel, D.C.; Kibiryeva, N.; Talebizadeh, Z.; Thompson, T. Behavioral differences among subjects with Prader-Willi syndrome and type I or type II deletion and maternal disomy. Pediatrics 2004, 113, 565–573.

Terms of Use/Privacy Policy/ Disclaimer/ Other Policies:
You agree that by using our site, you have read, understood, and agreed to be bound by all of our terms of use/privacy policy/ disclaimer/ other policies (click here for details).

This work and its PDF file(s) are licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.