Detection of a 22q11.2 deletion in cardiac patients suggests a risk for velopharyngeal incompetence.
Detection of a 22q11.2 deletion in cardiac patients suggests a risk for velopharyngeal incompetence.
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DOI：
10.1542/peds.99.5.e9
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发表时间：
1997-05
期刊：
影响因子：
8
通讯作者：
D. McDonald-McGinn;D. Driscoll;B. Emanuel;E. Goldmuntz;B. Clark;C. Solot;M. Cohen;Patricia Schultz;D. Larossa;Peter Randall;E. Zackai
中科院分区：
文献类型：
--
作者：
D. McDonald-McGinn;D. Driscoll;B. Emanuel;E. Goldmuntz;B. Clark;C. Solot;M. Cohen;Patricia Schultz;D. Larossa;Peter Randall;E. Zackai
目的DiGeorge或瓣膜心面综合征患者常发生心脏圆锥干畸形。此外，这些患者可能患有显性或粘膜下腭裂，以及腭咽闭合不全(VPI)。以往的研究表明，这些患者中的大多数存在22q11.2号染色体亚显微缺失。我们假设，由22q11.2缺失导致的新生儿和先天性心脏病儿童亚群具有未被识别的腭部异常的高风险。因此，我们建议评估与22q11.2缺失相关的圆锥干心脏畸形患者的队列，以确定腭部异常的频率。方法对14例缺失阳性的无明显腭裂的先天性心脏病患者进行分析。在对22q11.2缺失进行评估的14名患者中，有8名患者是从先前的一项研究中招募的，该研究在孤立性圆锥干心脏畸形患者中寻找缺失。在这些案件中，都获得了知情同意。其余的患者进行了临床基础上的缺失研究，即圆锥干心脏缺陷和胸腺缺失，免疫缺陷，或临床遗传学家认为的轻微变形。整形外科医生和语言病理学家对这些患者进行了评估，以寻找更细微的腭部异常，如粘膜下腭裂、肌肉悬垂缺失和VPI。一些患者根据他们的症状程度和年龄接受了视频透视或鼻内窥镜检查。直到得到言语病理学家和整形外科医生的客观评估，才排除VPI的可能性。此外，孩子必须年龄足够大，才能提供足够的语音样本。结果在接受评估的14例患者中，6例1岁以上的患者出现VPI。值得注意的是，这些患者中有3名年龄超过5岁，在本研究之前一直没有被识别出来。其余6名患者的研究基于他们的年龄(小于26个月)和他们不能参与适当的言语评估。然而，其中两名患者有提示VPI的鼻反流病史，此外，在鼻内窥镜检查中观察到的哭声和吞咽时，腭咽闭合机制不完全闭合-这与VPI的诊断一致。因此，在接受评估的14名患者中，有8名患者通过病史和检查有VPI的证据。其余6名患者在年龄较大时需要进一步研究，然后才能做出明确的腭裂诊断。结论心脏诊所中有相当数量的22q11.2缺失患者可能存在未被认识到的腭部问题。认识到这种异常将为患者提供必要的干预机会，即语音治疗和/或手术干预。值得注意的是，我们的两名患者发现VPI是婴儿，因此将有机会进行密切随访和早期干预。此外，三名学龄儿童有腭部异常，直到这项研究才被发现。因此，我们建议在圆锥干心脏畸形患者中进行22q11.2缺失研究，当存在缺失时，随后进行广泛的腭部和语音评估。
OBJECTIVE Conotruncal cardiac anomalies frequently occur in patients with DiGeorge or velocardiofacial syndrome. Additionally, these patients may have overt or submucousal cleft palate, as well as velopharyngeal incompetence (VPI). Previous studies have demonstrated that the majority of these patients have a submicroscopic deletion of chromosome 22q11.2. We hypothesized that a subpopulation of newborns and children with congenital heart defects caused by a 22q11.2 deletion are at a high risk for having unrecognized palatal abnormalities. Therefore, we proposed to evaluate a cohort of patients with conotruncal cardiac malformations associated with a 22q11.2 deletion to determine the frequency of palatal abnormalities. METHODS We identified 14 deletion-positive patients with congenital cardiac defects who had no overt cleft palate. Of the 14 patients evaluated for the 22q11.2 deletion, 8 patients were recruited from a previous study looking for deletions among patients with isolated conotruncal cardiac anomalies. Informed consent was obtained in these cases. The remaining patients had the deletion study on a clinical basis, ie, conotruncal cardiac defect and an absent thymus, immunodeficiency, or minor dysmorphia appreciated by the clinical geneticist. These patients were evaluated by a plastic surgeon and speech pathologist looking for more subtle palatal anomalies such as a submucousal cleft palate, absence of the musculous uvuli, and VPI. Some patients underwent videofluoroscopy or nasendoscopy depending on their degree of symptoms and age. VPI was not ruled out until objective evaluation by a speech pathologist and plastic surgeon was obtained. In addition, the child had to be old enough to provide an adequate speech sample. RESULTS Of the 14 patients evaluated, 6 patients older than 1 year were found to have VPI. It is noteworthy that 3 of these patients were older than 5 years and had remained unrecognized until this study. The remaining 6 patients had inconclusive studies based on their age (younger than 26 months) and their inability to participate in adequate speech evaluations. Two of these patients, however, had histories of nasal regurgitation suggesting VPI and, in addition, had incomplete closure of the velopharyngeal mechanism during crying and swallowing observed during nasendoscopic examination-consistent with the diagnosis of VPI. Thus, 8 of 14 patients evaluated had evidence of VPI by history and examination. The remaining 6 patients will require further study when they are older before a definitive palatal diagnosis can be made. CONCLUSIONS A significant number of patients with a 22q11.2 deletion in a cardiac clinic may have unrecognized palatal problems. Recognition of such abnormalities will afford patients the opportunity for intervention as needed, ie, speech therapy and/or surgical intervention. Notably, two of our patients with findings suggesting VPI were infants and will, therefore, be afforded the opportunity for close follow-up and early intervention. Furthermore, three school-aged children had palatal abnormalities that were unrecognized until this study. Thus, we recommend 22q11.2 deletion studies in patients with conotruncal cardiac malformations, followed by extensive palatal and speech evaluations when a deletion is present.