al-Gazali L I, Arthur R J, Lamb J T, Hammer H M, Coker T P, Hirschmann P N, Gibbs J, Mueller R F
Department of Genetic Counselling, General Infirmary at Leeds.
J Med Genet. 1989 Nov;26(11):694-703. doi: 10.1136/jmg.26.11.694.
Tuberous sclerosis (TS) results from an autosomal dominant gene which exhibits variable expression and reduced penetrance. Although there are well established diagnostic criteria for TS, examination of first degree relatives can cause diagnostic criteria for TS, examination of first degree relatives can cause diagnostic problems with consequent difficulties in genetic counselling. Using an extensive, non-invasive protocol consisting of skin examination with Wood's lamp, cranial CT scan, specialist ophthalmological and dental examination, skeletal survey, and echocardiography, we have examined 56 first degree relatives of persons with TS. These consisted of 40 parents and seven sibs from 25 sporadically affected families and nine persons from seven multigeneration families. In seven of the apparently sporadically affected families, three mothers had echocardiographical findings consistent with one or more rhabdomyoma. In another, the mother's renal ultrasound showed evidence of single cysts in both kidneys. In a fifth family, the father had suggestive but not diagnostic features of TS on the cranial CT scan and skeletal survey. In the sixth family, the mother was found to have atypical calcification on CT scan. In a seventh instance a sib from a two generation family had echocardiographical evidence of a rhabdomyoma. Even though the proband in three of the sporadically affected families presented with fits, developmental delay, and depigmented patches, and therefore did not strictly fulfil the diagnostic criteria for TS, two mothers were found to have evidence of rhabdomyomata on echocardiography and the brother of the third had typical depigmented patches. Although the presently accepted diagnostic criteria for TS may not allow one to make a definitive diagnosis of TS in these relatives, we recommend that an extensive screening protocol be used to examine first degree relatives and that caution be used in counselling apparently unaffected members of families at risk for TS.
结节性硬化症（TS）由常染色体显性基因引起，该基因表现出可变表达和降低的外显率。尽管已有完善的TS诊断标准，但对一级亲属进行检查可能会引发诊断问题，进而给遗传咨询带来困难。我们采用了一套广泛的非侵入性检查方案，包括伍德灯皮肤检查、头颅CT扫描、专科眼科和牙科检查、骨骼检查以及超声心动图检查，对56名TS患者的一级亲属进行了检查。这些亲属包括来自25个散发性患病家庭的40名父母和7名兄弟姐妹，以及来自7个多代患病家庭的9个人。在7个明显散发性患病的家庭中，3名母亲的超声心动图检查结果显示有一个或多个横纹肌瘤。在另一个家庭中，母亲的肾脏超声检查显示双肾有单个囊肿的迹象。在第五个家庭中，父亲的头颅CT扫描和骨骼检查显示有提示性但不具有诊断性的TS特征。在第六个家庭中，母亲的CT扫描发现有非典型钙化。在第七个例子中，一个两代家庭的兄弟姐妹有超声心动图证据显示有横纹肌瘤。尽管在3个散发性患病家庭中，先证者表现出癫痫发作、发育迟缓以及色素脱失斑，因此并未严格符合TS的诊断标准，但仍发现2名母亲的超声心动图检查有横纹肌瘤的证据，第三名先证者的兄弟有典型的色素脱失斑。尽管目前公认的TS诊断标准可能无法对这些亲属做出明确的TS诊断，但我们建议采用广泛的筛查方案对一级亲属进行检查，并在为TS风险家庭中看似未患病的成员提供咨询时谨慎行事。
