.: ORİJİNAL ARAŞTIRMA
Kromozom 22q11.2 Delesyon Sendromu Tanılı Hastaların Klinik ve Laboratuvar Özellikleri
Evaluation of the Clinical and Laboratory Findings of Patients with Chromosome 22q11.2 Deletion Syndrome
Turkiye Klinikleri J Pediatr. 2021;30(2):117-26
doi: 10.5336/pediatr.2021-81283
Makale Dili: TR
Tam Metin
Ücretsiz Erişim
ÖZET
Amaç: Bu çalışmada; kromozom 22q11.2 Delesyon Sendromu (22q11.2DS) tanısı konulan hastaların, genetik polikliniğine başvuru nedenleri ile birlikte, klinik ve laboratuvar bulgularının ayrıntılı olarak değerlendirilmesi amaçlandı. Ayrıca bu sendroma özgü fizik muayene bulgularına dikkat çekilerek, erken tanı ve izlemdeki önemleri vurgulandı. Gereç ve Yöntemler: Ocak 2014 ve Nisan 2018 tarihleri arasında 'Floresan in Situ Hibridizasyon Analizi' ile 22q11.2DS tanısı konulan 13 hasta çalışma kapsamına alındı. Hastaların başvuru yakınmaları, fizik ve dismorfik muayene bulguları, tanı alma yaşları, laboratuvar ve görüntüleme sonuçları, dosyalarından geriye dönük olarak incelenerek değerlendirildi. Bulgular: Hastaların, genetik polikliniğine en sık başvuru nedenleri; atipik yüz görünümü ve kardiyak anomali olarak saptandı. Hastalar, klinik bulgularına göre değerlendirildiğinde en sık bulgular; öğrenme geriliği (13 hasta; %100), doğumsal kalp anomalileri (12 hasta; %92,3) dismorfik yüz bulguları (11 hasta; %84,6) ve hipernazal konuşma (10 hasta; %76,9) idi. Dört (%30,9) hastada, yarık damak tespit edildi. Boy kısalığı 3 hastada görülürken, büyüme hormon eksikliği hiçbir hastada saptanmadı. Üç (%23) hastaya hipoparatiroidizm, 5 (%38,4) hastaya hipokalsemi ve 4 (%30,7) hastaya hipotiroidi tanısı konuldu. İki (%15,4) hastada ise timus hipoplazisi vardı. İskelet sistemi değerlendirilmesinde; 2 (%15,4) hastada skolyoz, 1 (%7,6) hastada platibazi ve 1 (%7,6) hastada pes ekinovarus deformitesi saptandı. Bağ dokusu problemi olarak; 3 (%23,1) hastada umblikal herni ve 1 (%7,6) hastada ise inguinal herni tespit edildi. Sonuç: 22q11.2DS'li hastalarda, majör klinik bulguların yanında, diğer sistemik bulguların varlığı da mutlaka araştırılmalıdır. Hastaları değerlendirirken özellikle; skolyoz, platibazi, umblikal ve inguinal herni gibi iskelet sistemi ve bağ dokusu anomalileri açısından da dikkatli olunmalıdır.
Anahtar Kelimeler: 22q11.2 Delesyon Sendromu; iskelet sistemi; skolyoz; platibazi; herni
Amaç: Bu çalışmada; kromozom 22q11.2 Delesyon Sendromu (22q11.2DS) tanısı konulan hastaların, genetik polikliniğine başvuru nedenleri ile birlikte, klinik ve laboratuvar bulgularının ayrıntılı olarak değerlendirilmesi amaçlandı. Ayrıca bu sendroma özgü fizik muayene bulgularına dikkat çekilerek, erken tanı ve izlemdeki önemleri vurgulandı. Gereç ve Yöntemler: Ocak 2014 ve Nisan 2018 tarihleri arasında 'Floresan in Situ Hibridizasyon Analizi' ile 22q11.2DS tanısı konulan 13 hasta çalışma kapsamına alındı. Hastaların başvuru yakınmaları, fizik ve dismorfik muayene bulguları, tanı alma yaşları, laboratuvar ve görüntüleme sonuçları, dosyalarından geriye dönük olarak incelenerek değerlendirildi. Bulgular: Hastaların, genetik polikliniğine en sık başvuru nedenleri; atipik yüz görünümü ve kardiyak anomali olarak saptandı. Hastalar, klinik bulgularına göre değerlendirildiğinde en sık bulgular; öğrenme geriliği (13 hasta; %100), doğumsal kalp anomalileri (12 hasta; %92,3) dismorfik yüz bulguları (11 hasta; %84,6) ve hipernazal konuşma (10 hasta; %76,9) idi. Dört (%30,9) hastada, yarık damak tespit edildi. Boy kısalığı 3 hastada görülürken, büyüme hormon eksikliği hiçbir hastada saptanmadı. Üç (%23) hastaya hipoparatiroidizm, 5 (%38,4) hastaya hipokalsemi ve 4 (%30,7) hastaya hipotiroidi tanısı konuldu. İki (%15,4) hastada ise timus hipoplazisi vardı. İskelet sistemi değerlendirilmesinde; 2 (%15,4) hastada skolyoz, 1 (%7,6) hastada platibazi ve 1 (%7,6) hastada pes ekinovarus deformitesi saptandı. Bağ dokusu problemi olarak; 3 (%23,1) hastada umblikal herni ve 1 (%7,6) hastada ise inguinal herni tespit edildi. Sonuç: 22q11.2DS'li hastalarda, majör klinik bulguların yanında, diğer sistemik bulguların varlığı da mutlaka araştırılmalıdır. Hastaları değerlendirirken özellikle; skolyoz, platibazi, umblikal ve inguinal herni gibi iskelet sistemi ve bağ dokusu anomalileri açısından da dikkatli olunmalıdır.
Anahtar Kelimeler: 22q11.2 Delesyon Sendromu; iskelet sistemi; skolyoz; platibazi; herni
ABSTRACT
Objective: It was aimed to evaluate in detail the clinical and laboratory findings of the patients diagnosed with chromosome 22q11.2 Deletion syndrome (22q11.2DS), together with the reasons for their application to the genetic clinic. In addition, by drawing attention to the physical examination findings specific to this syndrome, their importance in early diagnosis and follow-up was emphasized. Material and Methods: A total of 13 patients diagnosed with 22q11.2DS by Fluorescence in Situ Hybridization Analysis between January 2014 and April 2018 were included in this study. The causes of admission, physical and dysmorphic features, age of diagnosis, laboratory and imaging results of the patients were retrospectively evaluated from their medical records. Results: Atypical facial appearance and cardiac anomalies were the most common reasons for admission to genetic clinic. The most common features of the patients were learning disability (13 patients; 100%), congenital heart anomalies (12 patients; 92.3%), dysmorphic facial findings (11 patients; 84.6%), and hypernasal speech (10 patients; 76.9%). Cleft palate was seen in 4 patients (30.9%). While short stature was found in 3 patients, growth hormone deficiency was not detected in any of them. Hypoparathyroidism, hypocalcemia and hypothyroidism were seen in 3 patients (23%), 5 patients (%38.4), and 4 patients (30.7%), respectively. Two patients (15.4%) had thymus hypoplasia. During evaluation of skeletal system scoliosis, platybasia and pes equinovarus were observed in 2 patients (15.4%), 1 patient (7.6%), and 1 patient (7.6%) respectively. Connective tissue problems including, umbilical hernia (3 patients; 23.1%), and inguinal hernia (1 patient; 7.6%) were also noted. Conclusion: In addition to major clinical findings, the presence of other systemic findings should definitely be investigated in the evaluation of patients with 22q11.2DS. Care should be taken when evaluating patients with 22q11.2DS in terms of possible anomalies such as skeletal system and connective tissue pathologies including especially scoliosis, platibasia, umbilical and inguinal hernia.
Keywords: 22q11.2 Deletion Syndrome; skeletal system; scoliosis; platybasia; hernia
Objective: It was aimed to evaluate in detail the clinical and laboratory findings of the patients diagnosed with chromosome 22q11.2 Deletion syndrome (22q11.2DS), together with the reasons for their application to the genetic clinic. In addition, by drawing attention to the physical examination findings specific to this syndrome, their importance in early diagnosis and follow-up was emphasized. Material and Methods: A total of 13 patients diagnosed with 22q11.2DS by Fluorescence in Situ Hybridization Analysis between January 2014 and April 2018 were included in this study. The causes of admission, physical and dysmorphic features, age of diagnosis, laboratory and imaging results of the patients were retrospectively evaluated from their medical records. Results: Atypical facial appearance and cardiac anomalies were the most common reasons for admission to genetic clinic. The most common features of the patients were learning disability (13 patients; 100%), congenital heart anomalies (12 patients; 92.3%), dysmorphic facial findings (11 patients; 84.6%), and hypernasal speech (10 patients; 76.9%). Cleft palate was seen in 4 patients (30.9%). While short stature was found in 3 patients, growth hormone deficiency was not detected in any of them. Hypoparathyroidism, hypocalcemia and hypothyroidism were seen in 3 patients (23%), 5 patients (%38.4), and 4 patients (30.7%), respectively. Two patients (15.4%) had thymus hypoplasia. During evaluation of skeletal system scoliosis, platybasia and pes equinovarus were observed in 2 patients (15.4%), 1 patient (7.6%), and 1 patient (7.6%) respectively. Connective tissue problems including, umbilical hernia (3 patients; 23.1%), and inguinal hernia (1 patient; 7.6%) were also noted. Conclusion: In addition to major clinical findings, the presence of other systemic findings should definitely be investigated in the evaluation of patients with 22q11.2DS. Care should be taken when evaluating patients with 22q11.2DS in terms of possible anomalies such as skeletal system and connective tissue pathologies including especially scoliosis, platibasia, umbilical and inguinal hernia.
Keywords: 22q11.2 Deletion Syndrome; skeletal system; scoliosis; platybasia; hernia
REFERANSLAR:
- Kirkpatrick JA Jr, DiGeorge AM. Congenital absence of the thymus. Am J Roentgenol Radium Ther Nucl Med. 1968;103(1):32-7. [Crossref] [PubMed]
- McDonald-McGinn DM, Hain HS, Emanuel BS, Zackai EH. 22q11.2 Deletion Syndrome. In: Adam MP, Ardinger HH, Pagon RA, Wallace SE, Bean LJH, Stephens K, Amemiya A, eds. GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2020. [Link]
- Du Q, de la Morena MT, van Oers NSC. The genetics and epigenetics of 22q11.2 deletion syndrome. Front Genet. 2020;10:1365. [Crossref] [PubMed] [PMC]
- Palmer LD, Butcher NJ, Boot E, Hodgkinson KA, Heung T, Chow EWC, et al. Elucidating the diagnostic odyssey of 22q11.2 deletion syndrome. Am J Med Genet A. 2018;176(4):936-44. [Crossref] [PubMed] [PMC]
- Driscoll DA, Salvin J, Sellinger B, Budarf ML, McDonald-McGinn DM, Zackai EH, et al. Prevalence of 22q11 microdeletions in DiGeorge and velocardiofacial syndromes: implications for genetic counselling and prenatal diagnosis. J Med Genet. 1993;30(10):813-7. [Crossref] [PubMed] [PMC]
- Farrera A, Villanueva M, Vizcaíno A, Medina-Bravo P, Balderrábano-Saucedo N, Rives M, Cruz D, et al. Ontogeny of the facial phenotypic variability in Mexican patients with 22q11.2 deletion syndrome. Head Face Med. 2019;15(1):29. [Crossref] [PubMed] [PMC]
- Brown JJ, Datta V, Browning MJ, Swift PG. Graves' disease in DiGeorge syndrome: patient report with a review of endocrine autoimmunity associated with 22q11.2 deletion. J Pediatr Endocrinol Metab. 2004;17(11):1575-9. [Crossref] [PubMed]
- Göktürk B, Reisli İ. DiGeorge Sendromu [DiGeorge Syndrome]. Asthma Allergy Immunol.2016;14:129-42. [Crossref]
- Nepesov S, Aygün FD, Küçüksezer U, Taşdemir E, Çokuğraş H, Camcıoğlu Y. Clinical and immunophenotypic characteristics of patients with chromosome 22q11.2 deletion syndrome: a single institution's experience. Turk Pediatri Ars. 2019;54(1):28-34. [PubMed] [PMC]
- Jiramongkolchai P, Kumar MS, Sowder D, Chinnadurai S, Wootten CT, Goudy SL. Speech outcomes in children with 22q11.2 deletion syndrome following surgery for velopharyngeal insufficiency. Int J Pediatr Otorhinolaryngol. 2016;88:34-7. [Crossref] [PubMed]
- Goldmuntz E. 22q11.2 deletion syndrome and congenital heart disease. Am J Med Genet C Semin Med Genet. 2020;184(1):64-72. [Crossref] [PubMed]
- McDonald-McGinn DM, LaRossa D, Goldmuntz E, Sullivan K, Eicher P, Gerdes M, et al. The 22q11.2 deletion: screening, diagnostic workup, and outcome of results; report on 181 patients. Genet Test. 1997;1(2):99-108. [Crossref] [PubMed]
- Momma K. Cardiovascular anomalies associated with chromosome 22q11.2 deletion syndrome. Am J Cardiol. 2010;105(11):1617-24. [Crossref] [PubMed]
- Oskarsdóttir S, Persson C, Eriksson BO, Fasth A. Presenting phenotype in 100 children with the 22q11 deletion syndrome. Eur J Pediatr. 2005;164(3):146-53. [Crossref] [PubMed]
- Park IS, Ko JK, Kim YH, Yoo HW, Seo EJ, Choi JY, et al. Cardiovascular anomalies in patients with chromosome 22q11.2 deletion: a Korean multicenter study. Int J Cardiol. 2007;114(2):230-5. [Crossref] [PubMed]
- Derbent M, Yilmaz Z, Baltaci V, Saygili A, Varan B, Tokel K. Chromosome 22q11.2 deletion and phenotypic features in 30 patients with conotruncal heart defects. Am J Med Genet A. 2003;116A(2):129-35. [Crossref] [PubMed]
- Bousfiha A, Jeddane L, Picard C, Al-Herz W, Ailal F, Chatila T, et al. Human inborn errors of immunity: 2019 update of the IUIS phenotypical classification. J Clin Immunol. 2020;40(1):66-81. [Crossref] [PubMed] [PMC]
- Legitimo A, Bertini V, Costagliola G, Baroncelli GI, Morganti R, Valetto A, et al. Vitamin D status and the immune assessment in 22q11.2 deletion syndrome. Clin Exp Immunol. 2020;200(3):272-86. [Crossref] [PubMed] [PMC]
- Morsheimer M, Brown Whitehorn TF, Heimall J, Sullivan KE. The immune deficiency of chromosome 22q11.2 deletion syndrome. Am J Med Genet A. 2017;173(9):2366-72. [Crossref] [PubMed]
- Jawad AF, McDonald-Mcginn DM, Zackai E, Sullivan KE. Immunologic features of chromosome 22q11.2 deletion syndrome (DiGeorge syndrome/velocardiofacial syndrome). J Pediatr. 2001;139(5):715-23. [Crossref] [PubMed]
- Gennery AR, Barge D, O'Sullivan JJ, Flood TJ, Abinun M, Cant AJ. Antibody deficiency and autoimmunity in 22q11.2 deletion syndrome. Arch Dis Child. 2002;86(6):422-5. [Crossref] [PubMed] [PMC]
- Suksawat Y, Sathienkijkanchai A, Veskitkul J, Jirapongsananuruk O, Visitsunthorn N, Vichyanond P, et al. Resolution of Primary Immune Defect in 22q11.2 Deletion Syndrome. J Clin Immunol. 2017;37(4):375-82. [Crossref] [PubMed]
- Patel K, Akhter J, Kobrynski L, Benjamin Gathmann MA, Davis O, Sullivan KE; International DiGeorge Syndrome Immunodeficiency Consortium. Immunoglobulin deficiencies: the B-lymphocyte side of DiGeorge Syndrome. J Pediatr. 2012;161(5):950-3. Erratum in: J Pediatr. 2013;162(3):658. [Crossref] [PubMed]
- Cancrini C, Puliafito P, Digilio MC, Soresina A, Martino S, Rondelli R, et al; Italian Network for Primary Immunodeficiencies. Clinical features and follow-up in patients with 22q11.2 deletion syndrome. J Pediatr. 2014;164(6):1475-80.e2. [Crossref] [PubMed]
- Weinzimer SA. Endocrine aspects of the 22q11.2 deletion syndrome. Genet Med. 2001;3(1):19-22. [Crossref] [PubMed]
- Young D, Shprintzen RJ, Goldberg RB. Cardiac malformations in the velocardiofacial syndrome. Am J Cardiol. 1980;46(4):643-8. [Crossref] [PubMed]
- Goldberg R, Motzkin B, Marion R, Scambler PJ, Shprintzen RJ. Velo-cardio-facial syndrome: a review of 120 patients. Am J Med Genet. 1993;45(3):313-9. [Crossref] [PubMed]
- Weinzimer SA, McDonald-McGinn DM, Driscoll DA, Emanuel BS, Zackai EH, Moshang T Jr. Growth hormone deficiency in patients with 22q11.2 deletion: expanding the phenotype. Pediatrics. 1998;101(5):929-32. [Crossref] [PubMed]
- Ryan AK, Goodship JA, Wilson DI, Philip N, Levy A, Seidel H, et al. Spectrum of clinical features associated with interstitial chromosome 22q11 deletions: a European collaborative study. J Med Genet. 1997;34(10):798-804. [Crossref] [PubMed] [PMC]
- Shugar AL, Shapiro JM, Cytrynbaum C, Hedges S, Weksberg R, Fishman L. An increased prevalence of thyroid disease in children with 22q11.2 deletion syndrome. Am J Med Genet A. 2015;167(7):1560-4. [Crossref] [PubMed]
- Verheij E, Derks LSM, Stegeman I, Thomeer HGXM. Prevalence of hearing loss and clinical otologic manifestations in patients with 22q11.2 deletion syndrome: A literature review. Clin Otolaryngol. 2017;42(6):1319-28. [Crossref] [PubMed]
- Homans JF, Baldew VGM, Brink RC, Kruyt MC, Schlösser TPC, Houben ML, et al. Scoliosis in association with the 22q11.2 deletion syndrome: an observational study. Arch Dis Child. 2019;104(1):19-24. [Crossref] [PubMed]
- Glander K 2nd, Cisneros GJ. Comparison of the craniofacial characteristics of two syndromes associated with the Pierre Robin sequence. Cleft Palate Craniofac J. 1992;29(3):210-9. [Crossref] [PubMed]
- Gokturk B, Guner SN, Kara R, Kirac M, Keles S, Artac H, et al. Would mean platelet volume/platelet count ratio be used as a novel formula to predict 22q11.2 deletion syndrome? Asian Pac J Allergy Immunol. 2016;34(2):166-73. [PubMed]
- Barnett C, Langer JC, Hinek A, Bradley TJ, Chitayat D. Looking past the lump: genetic aspects of inguinal hernia in children. J Pediatr Surg. 2009;44(7):1423-31. [Crossref] [PubMed]
.: İşlem Listesi