A Novel Case of SHORT Syndrome Presenting with Very Early Onset Inflammatory Bowel Disease (VEO-IBD)
Abstract
Herein we report a novel case of SHORT syndrome with very early onset inflammatory bowel disease (VEO-
IBD). He presented with hematochezia since the first months of life for which he was diagnosed with cow
milk allergy that did not respond to treatment. He underwent a colonoscopy confirming the diagnosis of
ulcerative colitis (UC). His past medical history was also remarkable with delayed growth since 6 months
of age and frequent hospitalizations due to recurrent fever, gastroenteritis, and anemia with no history of
recurrent infectious episodes. Despite appropriate treatment for UC and partial improvement in his bowel
habits and nutrition, there was no improvement in his growth status and he was found to have failure to
thrive. The patient further underwent genetic test evaluation and a novel heterozygous missense mutation
was detected in the PIK3R1 gene (c.2076A>C, P. Lys692Asn) confirming the diagnosis of SHORT syndrome.
He got appropriate treatment and is currently doing well, in good condition and is under regular monthly
follow-up.
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2. Lipson, Cowell, Gorlin. The SHORT syndrome: further delineation and natural history. J Med Genet. 1989;26(7):473.
3. Avila, Dyment, Sagen, St-Onge, Moog, Chung, et al. Clinical reappraisal of SHORT syndrome with PIK3R1 mutations: toward recommendation for molecular testing and management. Clin Genet. 2016;89(4):501-6.
4. Chudasama, Winnay, Johansson, Claudi, König, Haldorsen, et al. SHORT syndrome with partial lipodystrophy due to impaired phosphatidylinositol 3 kinase signaling. Am J Hum Genet. 2013;93(1):150-7.
5. Dyment, Smith, Alcantara, Schwartzentruber, Basel-Vanagaite, Curry, et al. Mutations in PIK3R1 cause SHORT syndrome. Am J Hum Genet. 2013;93(1):158-66.
6. Walsh, Fruman. Too much of a good thing: immunodeficiency due to hyperactive PI3K signaling. J Clin Invest. 2014;124(9):3688-90.
7. Koyasu. The role of PI3K in immune cells. Nat Immunol. 2003;4(4):313-9.
8. Okkenhaug, Vanhaesebroeck. PI3K in lymphocyte development, differentiation and activation. Nat Rev Immunol. 2003;3(4):317-30.
9. Sauer, Huang, Lin, Sandberg, Mayr. Phosphoinositide and inositol phosphate analysis in lymphocyte activation. Curr Protoc Immunol. 2009;Chapter 11(1):11 1 1- 1 46.
10. García-Morato, García-Miñaúr, Garicano, Simarro, Molina, López-Granados, et al. Mutations in PIK3R1 can lead to APDS2, SHORT syndrome or a combination of the two. Clin Immunol. 2017;179:77-80.
11. Uhlig, Schwerd, Koletzko, Shah, Kammermeier, Elkadri, et al. The diagnostic approach to monogenic very early onset inflammatory bowel disease. Gastroenterology. 2014;147(5):990-1007. e3.
12. Muise, Snapper, Kugathasan. The age of gene discovery in very early onset inflammatory bowel disease. Gastroenterology. 2012;143(2):285-8.
13. Oliva-Hemker, Hutfless, Al Kazzi, Lerer, Mack, LeLeiko, et al. Clinical presentation and five-year therapeutic management of very early-onset inflammatory bowel disease in a large North American cohort. J Pediatr. 2015;167(3):527-32. e3.
14. Pazmandi, Kalinichenko, Ardy, Boztug. Early‐onset inflammatory bowel disease as a model disease to identify key regulators of immune homeostasis mechanisms. Immunol Rev. 2019;287(1):162-85.
15. Kelsen, Baldassano, Artis, Sonnenberg. Maintaining intestinal health: the genetics and immunology of very early onset inflammatory bowel disease. Cell Mol Gastroenterol. 2015;1(5):462-76.
16. Ouahed, Spencer, Kotlarz, Shouval, Kowalik, Peng, et al. Very early onset inflammatory bowel disease: a clinical approach with a focus on the role of genetics and underlying immune deficiencies. Inflamm Bowel Dis. 2020;26(6):820-42.
17. Bravo Garcia-Morato, Garcia-Minaur, Molina Garicano, Santos Simarro, Del Pino Molina, Lopez-Granados, et al. Mutations in PIK3R1 can lead to APDS2, SHORT syndrome or a combination of the two. Clin Immunol. 2017;179:77-80.
18. Sun, Zhang, Li, Tang, Wang, Li, et al. A novel PIK3R1 mutation of SHORT syndrome in a Chinese female with diffuse thyroid disease: a case report and review of literature. BMC Med Genet. 2020;21:1-7.
19. Fekrvand, Delavari, Chavoshzadeh, Sherkat, Mahdaviani, Sadeghi Shabestari, et al. The first iranian cohort of pediatric patients with activated phosphoinositide 3-kinase-δ (PI3Kδ) syndrome (APDS). IMMUNOL INVEST. 2022;51(3):644-59.
20. Yazdani, Hamidi, Babaha, Azizi, Fekrvand, Abolhassani, et al. PIK3R1 Mutation Associated with Hyper IgM (APDS2 Syndrome): A Case Report and Review of the Literature. Endocr Metab Immune Disord Drug Targets. 2019;19(7):941-58.
21. Tang, Upton, Barton-Forbes, Salvadori, Clynick, Price, et al. Autosomal recessive agammaglobulinemia due to a homozygous mutation in PIK3R1. J Clin Immunol. 2018;38:88-95.
22. Conley, Dobbs, Quintana, Bosompem, Wang, Coustan-Smith, et al. Agammaglobulinemia and absent B lineage cells in a patient lacking the p85α subunit of PI3K. J Exp Med. 2012;209(3):463-70.
23. Yu, Cui. Proliferation, survival and metabolism: the role of PI3K/AKT/mTOR signalling in pluripotency and cell fate determination. Development. 2016;143(17):3050-60.
24. Patel, Cui, Cobben. SHORT syndrome with microcephaly and developmental delay. Am J Med Genet A. 2023;191(3):850-4.
25. Gonçalves, Moretti, Cordoba, Oliveira, Lopes, Oliveira, et al. SHORT syndrome in an adult Brazilian patient. Am J Med Genet A. 2022;188(5):1635-8.
26. Reardon, Temple. Nephrocalcinosis and disordered calcium metabolism in two children with SHORT syndrome. Am J Med Genet A. 2008;146A(10):1296-8.
27. Badeński, Stojewska, Ziora, Badeńska, Bjanid, Sobczyńska-Tomaszewska, et al. SHORT syndrome in an 11-year-old boy–case report. Pediatr Pol Pedjatr Pol. 2019;94(6):379-84.
2. Lipson, Cowell, Gorlin. The SHORT syndrome: further delineation and natural history. J Med Genet. 1989;26(7):473.
3. Avila, Dyment, Sagen, St-Onge, Moog, Chung, et al. Clinical reappraisal of SHORT syndrome with PIK3R1 mutations: toward recommendation for molecular testing and management. Clin Genet. 2016;89(4):501-6.
4. Chudasama, Winnay, Johansson, Claudi, König, Haldorsen, et al. SHORT syndrome with partial lipodystrophy due to impaired phosphatidylinositol 3 kinase signaling. Am J Hum Genet. 2013;93(1):150-7.
5. Dyment, Smith, Alcantara, Schwartzentruber, Basel-Vanagaite, Curry, et al. Mutations in PIK3R1 cause SHORT syndrome. Am J Hum Genet. 2013;93(1):158-66.
6. Walsh, Fruman. Too much of a good thing: immunodeficiency due to hyperactive PI3K signaling. J Clin Invest. 2014;124(9):3688-90.
7. Koyasu. The role of PI3K in immune cells. Nat Immunol. 2003;4(4):313-9.
8. Okkenhaug, Vanhaesebroeck. PI3K in lymphocyte development, differentiation and activation. Nat Rev Immunol. 2003;3(4):317-30.
9. Sauer, Huang, Lin, Sandberg, Mayr. Phosphoinositide and inositol phosphate analysis in lymphocyte activation. Curr Protoc Immunol. 2009;Chapter 11(1):11 1 1- 1 46.
10. García-Morato, García-Miñaúr, Garicano, Simarro, Molina, López-Granados, et al. Mutations in PIK3R1 can lead to APDS2, SHORT syndrome or a combination of the two. Clin Immunol. 2017;179:77-80.
11. Uhlig, Schwerd, Koletzko, Shah, Kammermeier, Elkadri, et al. The diagnostic approach to monogenic very early onset inflammatory bowel disease. Gastroenterology. 2014;147(5):990-1007. e3.
12. Muise, Snapper, Kugathasan. The age of gene discovery in very early onset inflammatory bowel disease. Gastroenterology. 2012;143(2):285-8.
13. Oliva-Hemker, Hutfless, Al Kazzi, Lerer, Mack, LeLeiko, et al. Clinical presentation and five-year therapeutic management of very early-onset inflammatory bowel disease in a large North American cohort. J Pediatr. 2015;167(3):527-32. e3.
14. Pazmandi, Kalinichenko, Ardy, Boztug. Early‐onset inflammatory bowel disease as a model disease to identify key regulators of immune homeostasis mechanisms. Immunol Rev. 2019;287(1):162-85.
15. Kelsen, Baldassano, Artis, Sonnenberg. Maintaining intestinal health: the genetics and immunology of very early onset inflammatory bowel disease. Cell Mol Gastroenterol. 2015;1(5):462-76.
16. Ouahed, Spencer, Kotlarz, Shouval, Kowalik, Peng, et al. Very early onset inflammatory bowel disease: a clinical approach with a focus on the role of genetics and underlying immune deficiencies. Inflamm Bowel Dis. 2020;26(6):820-42.
17. Bravo Garcia-Morato, Garcia-Minaur, Molina Garicano, Santos Simarro, Del Pino Molina, Lopez-Granados, et al. Mutations in PIK3R1 can lead to APDS2, SHORT syndrome or a combination of the two. Clin Immunol. 2017;179:77-80.
18. Sun, Zhang, Li, Tang, Wang, Li, et al. A novel PIK3R1 mutation of SHORT syndrome in a Chinese female with diffuse thyroid disease: a case report and review of literature. BMC Med Genet. 2020;21:1-7.
19. Fekrvand, Delavari, Chavoshzadeh, Sherkat, Mahdaviani, Sadeghi Shabestari, et al. The first iranian cohort of pediatric patients with activated phosphoinositide 3-kinase-δ (PI3Kδ) syndrome (APDS). IMMUNOL INVEST. 2022;51(3):644-59.
20. Yazdani, Hamidi, Babaha, Azizi, Fekrvand, Abolhassani, et al. PIK3R1 Mutation Associated with Hyper IgM (APDS2 Syndrome): A Case Report and Review of the Literature. Endocr Metab Immune Disord Drug Targets. 2019;19(7):941-58.
21. Tang, Upton, Barton-Forbes, Salvadori, Clynick, Price, et al. Autosomal recessive agammaglobulinemia due to a homozygous mutation in PIK3R1. J Clin Immunol. 2018;38:88-95.
22. Conley, Dobbs, Quintana, Bosompem, Wang, Coustan-Smith, et al. Agammaglobulinemia and absent B lineage cells in a patient lacking the p85α subunit of PI3K. J Exp Med. 2012;209(3):463-70.
23. Yu, Cui. Proliferation, survival and metabolism: the role of PI3K/AKT/mTOR signalling in pluripotency and cell fate determination. Development. 2016;143(17):3050-60.
24. Patel, Cui, Cobben. SHORT syndrome with microcephaly and developmental delay. Am J Med Genet A. 2023;191(3):850-4.
25. Gonçalves, Moretti, Cordoba, Oliveira, Lopes, Oliveira, et al. SHORT syndrome in an adult Brazilian patient. Am J Med Genet A. 2022;188(5):1635-8.
26. Reardon, Temple. Nephrocalcinosis and disordered calcium metabolism in two children with SHORT syndrome. Am J Med Genet A. 2008;146A(10):1296-8.
27. Badeński, Stojewska, Ziora, Badeńska, Bjanid, Sobczyńska-Tomaszewska, et al. SHORT syndrome in an 11-year-old boy–case report. Pediatr Pol Pedjatr Pol. 2019;94(6):379-84.
| Files | ||
| Issue | Vol 6, No 1 (2023) | |
| Section | Case Report | |
| DOI | https://doi.org/10.18502/igj.v6i1.16343 | |
| Keywords | ||
| Activated p110δ Syndrome Primary Immunodeficiency Disorders PIK3R1 SHORT Syndrome Very Early Onset Inflammatory Disease | ||
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This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License. |
How to Cite
1.
Fekrvand S, Shahrooei M, Sadeghi_Shabestari M. A Novel Case of SHORT Syndrome Presenting with Very Early Onset Inflammatory Bowel Disease (VEO-IBD). Immunol Genet J. 2023;6(1):34-38.
