Extreme variability of expression of a Sonic Hedgehog mutation: attention difficulties and holoprosencephaly (original) (raw)
Extreme variability of expression of a Sonic Hedgehog mutation: attention difficulties and holoprosencephaly
- H S Heussler1,
- M Suri2,
- I D Young3,
- M Muenke4
- 1Academic Division of Child Health, University of Nottingham, Nottingham NG7 2UH, UK
- 2City Hospital, Hucknall Rd, Nottingham NG5 1PB, UK
- 3Leicester Royal Infirmary, Leicester LE1 5WW, UK
- 4Medical Genetics Branch, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD 20892, USA
- Correspondence to:
Dr H S Heussler, Academic Division of Child Health, University of Nottingham, Nottingham NG7 2UH, UK;
honey.heussler{at}nottingham.ac.uk
Abstract
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.
- holoprosencephaly, attention deficit hyperactivity disorder
- sonic hedgehog
- gene
- ADHD, attention deficit hyperactivity disorder
- CNS, central nervous system
- CT, computed tomography
- HPE, holoprosencephaly
- MRI, magnetic resonance imaging
- Ptch, patched transmembrane receptor
- Smo, smoothened transmembrane receptor
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