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

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 inc...

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Bibliographic Details
Published in:Archives of disease in childhood 2002-04, Vol.86 (4), p.293-296
Main Authors: Heussler, H S, Suri, M, Young, I D, Muenke, M
Format: Article
Language:English
Subjects:
ADHD
Adult
Age
Attention Deficit Disorder with Hyperactivity - genetics
Attention Deficit Disorders
attention deficit hyperactivity disorder
Biological and medical sciences
Body Weight
central nervous system
Child Health
Clinical Diagnosis
CNS
Complex syndromes
computed tomography
Congenital Impairments
Developmental Delays
Families & family life
Family (Sociological Unit)
Female
gene
Genes
Genetic aspects
Hedgehog Proteins
Holoprosencephaly
Holoprosencephaly - genetics
HPE
Humans
Infant
Insects
Interpersonal Competence
Learning disabilities
Learning Problems
magnetic resonance imaging
Male
Medical genetics
Medical sciences
Mothers
MRI
Mutation
Mutation - genetics
NMR
Nuclear magnetic resonance
Original
patched transmembrane receptor
Pedigree
Perceptual Motor Coordination
Pregnancy
Ptch
Smo
smoothened transmembrane receptor
Social skills
sonic hedgehog
Special Schools
Speech
Trans-Activators - genetics
Ultrasonic imaging
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Description
Summary: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.
ISSN:0003-9888
1468-2044
DOI:10.1136/adc.86.4.293