Solomon B D, Pineda-Alvarez D E, Gropman A L, Willis M J, Hadley D W, Muenke M
Medical Genetics Branch, Naval Medical Center, San Diego, Calif., USA.
Mol Syndromol. 2012 Sep;3(3):140-142. doi: 10.1159/000341373. Epub 2012 Jul 26.
Holoprosencephaly is the most common malformation of the forebrain and typically results in severe neurocognitive impairment with accompanying midline facial anomalies. Holoprosencephaly is heterogeneous and may be caused by chromosome aberrations or environmental factors, occur in the context of a syndrome or be due to heterozygous mutations in over 10 identified genes. The presence of these mutations may result in an extremely wide spectrum of severity, ranging from brain malformations incompatible with life to individuals with normal brain findings and subtle midline facial differences. Typically, clinicians regard intellectual disability as a sign that a parent or relative of a severely affected patient may be a mildly affected mutation 'carrier' with what is termed microform holoprosencephaly. Here we present 5 patients with clear phenotypic signs of microform holoprosencephaly, all of whom have evidence of above-average intellectual function. In 4 of these 5 individuals, the molecular cause of holoprosencephaly has been identified and includes mutations affecting SHH, SIX3, GLI2, and FGF8. This report expands the phenotypic spectrum of holoprosencephaly and is important in the counseling of patient and affected families.
前脑无裂畸形是最常见的前脑畸形，通常会导致严重的神经认知障碍，并伴有中线面部异常。前脑无裂畸形具有异质性，可能由染色体畸变或环境因素引起，可在综合征背景下出现，或归因于超过10个已确定基因中的杂合突变。这些突变的存在可能导致极其广泛的严重程度范围，从与生命不相容的脑畸形到脑检查结果正常但有细微中线面部差异的个体。通常，临床医生认为智力残疾是一个迹象，表明严重受影响患者的父母或亲属可能是患有所谓微小畸形型前脑无裂畸形的轻度受影响突变“携带者”。在此，我们报告了5例具有明显微小畸形型前脑无裂畸形表型体征的患者，所有患者均有智力功能高于平均水平的证据。在这5例患者中的4例中，已确定前脑无裂畸形的分子病因，包括影响SHH、SIX3、GLI2和FGF8的突变。本报告扩展了前脑无裂畸形的表型谱，对患者及受影响家庭的咨询具有重要意义。
