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.