NOONAN SYNDROME - THE CHANGING PHENOTYPE
NOONAN SYNDROME - THE CHANGING PHENOTYPE
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DOI：
10.1002/ajmg.1320210313
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发表时间：
1985-01-01
期刊：
影响因子：
--
通讯作者：
WITT, RD
中科院分区：
文献类型：
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作者：
ALLANSON, JE;HALL, JG;WITT, RD
在多发性先天性畸形(MCA)综合征中，Noonan综合征(NS)是一种心面部综合征，患者可能是矮小和轻度智力低下的人。常染色体显性遗传的Noonan综合征具有可变的表达能力，已在许多家庭中被记录在案。Noonan综合征的遗传异质性被认为是因为广泛的表型变异，相对较高的发生率，以及父母明显正常的同胞中偶尔会复发。临床变异性在常染色体显性遗传病中很常见，轻度受累的个体可能很难识别为基因携带者。因此，一个有两个或更多受影响子女的家庭可能会模拟常染色体隐性遗传。为了评估基因携带者在遗传学研究中被遗漏的可能性，研究了NS患者的连续照片和家庭照片。证实了家庭内广泛的临床变异性，更重要的是，从新生儿期、婴儿期、儿童期和青春期到成年，表型随年龄的显著变化被记录在案。成年人的症状可能很微妙，一些没有已知心脏缺陷或其他医学上重大问题的患者在过去可能被认为是正常的。这项研究虽然没有排除因果异质性，但建议必须在受影响儿童的父母中寻找表型变化。
Among the multiple congenital anomalies (MCA) syndromes, the Noonan syndrome (NS) is a cardiofacial syndrome in which affected individuals may be short and mildly mentally retarded. Autosomal dominant inheritance of Noonan syndrome with variable expressivity has been documented in many families. Genetic heterogeneity has been postulated in Noonan syndrome because of the wide phenotypic variability, the relatively high incidence, and the occasional recurrence in sibs with apparently normal parents. Clinical variability is usual in autosomal dominant disorders, and mildly affected individuals may be difficult to recognize as gene carriers. Thus, a family with 2 or more affected children may simulate autosomal ecessive inheritance. Serial and family photographs of NS individuals were studied in order to assess the likelihood of gene carriers'' being missed in genetic studies. Wide clinical variability within families was confirmed and more importantly, marked change of phenotype with age from the newborn period, infancy, childhood, and adolescence to adulthood was documented. Manifestations in adults may be subtle and some without a known heart defect or other medically signficant problems may have been considered normal in the past. The study, while not ruling out causal heterogeneity, suggests that the change of phenotype must be searched for in parents of affected children.