IMAGe association: Additional clinical features and evidence for recessive autosomal inheritance
IMAGe association: Additional clinical features and evidence for recessive autosomal inheritance
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DOI：
10.1159/000058105
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发表时间：
2002-01-01
期刊：
影响因子：
--
通讯作者：
Tauber, M
中科院分区：
文献类型：
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作者：
Lienhardt, A;Mas, JC;Tauber, M
先天性肾上腺发育不良(CAN)通常发生在新生儿期，患者出现或多或少严重的盐耗综合征。X连锁CAH与DAX-1基因突变有关，男孩也被证明患有性腺激素减退症。最近，在三个没有血缘关系的男孩中，CAH与宫内发育迟缓(IUGR)、干骺端发育不良和生殖器异常有关，定义了一个新的关联，称为IMAGE。我们现在报告另外四名与此相关的患者，包括第一例活着的女性。这四名患者属于两个无亲属关系的家庭(每个家庭各有一名兄弟和一名姐妹)。这些患者具有影像联想的主要临床特征：IUGR、面部畸形(额部隆起、鼻桥宽阔、耳朵低垂)、干骺端发育不良所致肢体短小、肾上腺功能不全。由于这些患者比最初的三名患者年龄更大，我们还可以描述其他特征：成年身高较短，男孩和活着的女孩都有正常的青春期。这两个男孩有与小阴茎相关的尿道下裂。这名活着的女孩因家族性调查而在5岁时得到临床关注，仔细询问后发现，她从小就患有轻度肾上腺皮质功能不全。至少有一名男孩因肌肉营养不良而患有先天性低眼压症。综上所述，这4例新病例表现为家族性遗传，强烈提示孟德尔常染色体隐性遗传。肾上腺功能不全可能是轻微的。在所有患者中描述的低眼压可能与缺乏症状性肌营养不良有关，因为这种情况在严重程度、相关表现和结果方面明显不同。如果这种症状是综合症的一部分，我们不能假设，这可能有助于定位候选基因。版权所有(C)2002 S.KargerAG，巴塞尔。
Congenital adrenal hypoplasia (CAN) normally occurs in the neonatal period, with patients presenting with more or less severe salt-wasting syndrome. X-linked CAH has been associated with mutations in the DAX-1 gene, and boys have also been shown to have hypogonadotrophic hypogonadism. Recently, in three unrelated boys, CAH was associated with intrauterine growth retardation (IUGR), metaphyseal dysplasia and genital abnormalities, defining a new association called IMAGe. We now report four additional patients with this association, including the first living female. The four patients belong to two unrelated families (one brother and one sister from each family). These patients have the main clinical characteristics of IMAGe association: IUGR, facial dysmorphy (frontal bossing, broad nasal bridge, low-set ears), short limbs due to metaphyseal dysplasia, and adrenal insufficiency. As these patients are older than the initial three patients, we can also describe additional features: short adult height, normal puberty in boys as well as in the living girl. The boys have hypospadias associated with micropenis. The living girl came to clinical attention at the age of 5 years as a result of a familial survey, and careful questioning revealed that she had been suffering from mild adrenal insufficiency since early childhood. At least one boy has congenital hypotonia due to muscular dystrophy. In conclusion, these four new cases display familial transmission, strongly suggesting Mendelian autosomal recessive inheritance. Adrenal insufficiency may be mild. Hypotonia, described in all the patients, might be related to paucisymptomatic muscular dystrophy, as this condition is clearly heterogeneous varying with regard to severity, associated manifestations and outcome. If this symptom is part of the syndrome, which we cannot assume, it could help to localize the candidate gene. Copyright (C) 2002 S. KargerAG, Basel.