High Intellectual Function in Individuals with Mutation-Positive Microform Holoprosencephaly

Molecular Syndromology

M.J. Willis¹  D.E. Pineda-Alvarez¹  A.L. Gropman¹  D.W. Hadley¹  M. Muenke¹  B.D. Solomon¹ 

[1] aMedical Genetics Branch, Naval Medical Center, San Diego, Calif., USA

关键词: FGF8;    GLI2;    Holoprosencephaly;    HPE;    Microform;    SHH;    SIX3;    Sonic Hedgehog;   

DOI  :  10.1159/000341373

学科分类：基础医学

来源: S Karger AG

【 摘 要 】

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.

【 授权许可】

Unknown