Grassi Marcília S, Jacob Cristina M A, Kulikowski Leslie D, Pastorino Antonio C, Dutra Roberta L, Miura Nana, Jatene Marcelo B, Pegler Stephanie P, Kim Chong A, Carneiro-Sampaio Magda
Instituto da Criança, HC, FMUSP, São Paulo, SP, Brazil.
Departamento de Patologia, Faculdade de Medicina, Universidade de São Paulo, São Paulo, SP, Brazil.
Arq Bras Cardiol. 2014 Nov;103(5):382-390. doi: 10.5935/abc.20140145. Epub 2014 Oct 10.
Background: To alert for the diagnosis of the 22q11.2 deletion syndrome (22q11.2DS) in patients with congenital heart disease (CHD). Objective: To describe the main CHDs, as well as phenotypic, metabolic and immunological findings in a series of 60 patients diagnosed with 22q11.2DS. Methods: The study included 60 patients with 22q11.2DS evaluated between 2007 and 2013 (M:F=1.3, age range 14 days to 20 years and 3 months) at a pediatric reference center for primary immunodeficiencies. The diagnosis was established by detection of the 22q11.2 microdeletion using FISH (n = 18) and/or MLPA (n = 42), in association with clinical and laboratory information. Associated CHDs, progression of phenotypic facial features, hypocalcemia and immunological changes were analyzed. Results: CHDs were detected in 77% of the patients and the most frequent type was tetralogy of Fallot (38.3%). Surgical correction of CHD was performed in 34 patients. Craniofacial dysmorphisms were detected in 41 patients: elongated face (60%) and/or elongated nose (53.3%), narrow palpebral fissure (50%), dysplastic, overfolded ears (48.3%), thin lips (41.6%), elongated fingers (38.3%) and short stature (36.6%). Hypocalcemia was detected in 64.2% and decreased parathyroid hormone (PTH) level in 25.9%. Decrease in total lymphocytes, CD4 and CD8 counts were present in 40%, 53.3% and 33.3%, respectively. Hypogammaglobulinemia was detected in one patient and decreased concentrations of immunoglobulin M (IgM) in two other patients. Conclusion: Suspicion for 22q11.2DS should be raised in all patients with CHD associated with hypocalcemia and/or facial dysmorphisms, considering that many of these changes may evolve with age. The 22q11.2 microdeletion should be confirmed by molecular testing in all patients.
提高对先天性心脏病（CHD）患者22q11.2缺失综合征（22q11.2DS）的诊断警惕性。目的：描述一系列60例诊断为22q11.2DS患者的主要先天性心脏病，以及其表型、代谢和免疫学表现。方法：该研究纳入了60例2007年至2013年间在一家原发性免疫缺陷病儿科参考中心接受评估的22q11.2DS患者（男∶女 = 1.3，年龄范围为14天至20岁零3个月）。通过荧光原位杂交（FISH，n = 18）和/或多重连接探针扩增技术（MLPA，n = 42）检测22q11.2微缺失，并结合临床和实验室信息来确诊。分析相关的先天性心脏病、面部特征表型进展、低钙血症和免疫学变化。结果：77%的患者检测到先天性心脏病，最常见的类型是法洛四联症（38.3%）。34例患者接受了先天性心脏病的手术矫正。41例患者检测到颅面部畸形：长脸（60%）和/或长鼻（53.3%）、睑裂狭窄（50%）、发育异常且折叠过度的耳朵（48.3%）、薄唇（41.6%）、手指细长（38.3%）和身材矮小（36.6%）。64.2%的患者检测到低钙血症，25.9%的患者甲状旁腺激素（PTH）水平降低。总淋巴细胞、CD4和CD8计数分别在40%、53.3%和33.3%的患者中出现下降。1例患者检测到低丙种球蛋白血症，另外2例患者免疫球蛋白M（IgM）浓度降低。结论：对于所有伴有低钙血症和/或面部畸形的先天性心脏病患者，应怀疑22q11.2DS，因为这些变化中的许多可能会随年龄发展。所有患者均应通过分子检测来确诊22q11.2微缺失。
