Extreme variability of expression of a Sonic Hedgehog mutation: attention difficulties and holoprosencephaly

被引:56
作者
Heussler, HS [1 ]
Suri, M
Young, ID
Muenke, M
机构
[1] Univ Nottingham, Acad Div Child Hlth, Nottingham NG7 2UH, England
[2] City Hosp, Nottingham NG5 1PB, England
[3] Leicester Royal Infirm, Leicester LE1 5WW, Leics, England
[4] Natl Human Genome Res Inst, Med Genet Branch, NIH, Bethesda, MD 20892 USA
关键词
D O I
10.1136/adc.86.4.293
中图分类号
R72 [儿科学];
学科分类号
100202 ;
摘要
Holoprosencephaly (HPE) is a clinically variable and genetically heterogeneous central nervous system (CNS) malformation. Alobar HPE, which is its most severe form, is associated with a poor prognosis. At the milder end of the HPE spectrum microcephaly, hypotelorism, and single central maxillary incisor may be recognised. Currently, four genes have been identified for this condition. These include Sonic Hedgehog (SHH) on chromosome 7q36, which is thought to be responsible for a significant proportion of autosomal dominant HPE. We report an index case with alobar holoprosencephaly caused by an SHH mutation and six members of his family over two generations with this mutation, with a broad range of clinical presentation, including attention deficit hyperactivity disorder (ADHD). The combination of microcephaly, hypotelorism, subtle midline facial anomalies, and ADHD within a sibship should alert the physician to the possible diagnosis of HPE.
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页码:293 / 296
页数:4
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