Passemard Sandrine, Kaindl Angela M, Verloes Alain
Department of Genetics, Hôpital Robert Debré, Paris, France; Inserm U676 and Medical School, Denis Diderot-Paris VII University, Paris, France.
Handb Clin Neurol. 2013;111:129-41. doi: 10.1016/B978-0-444-52891-9.00013-0.
True microcephaly (head circumference ≤-3SD), either primary (present at birth) or secondary (of postnatal onset) results from an imbalance between progenitor cell production and cell death that lead to a reduced number of neuronal and glial cells within the brain, resulting in reduced brain growth. Primary non-syndromal microcephalies are recessive disorders resulting from abnormal control of mitotic spindle and cell cycle kinetics in progenitor cells. Microcephaly is also a frequent sign of defects in DNA double- and/or single-strand break repair and in nucleotide excision repair, in which it often is associated with general growth impairment. In these etiologies, cognitive functions are reasonably well preserved despite severe reduction in brain volume. Neuronal migration defects are often associated with secondary microcephaly, as are anomalies of telencephalic cleavage. Secondary microcephalies are often associated with increased neuronal death, and can be associated with metabolic disorders such as serine deficiency or thiamine pyrophosphate transporter deficiency. Microcephaly can be associated with hundreds of syndromal congenital anomalies, including many chromosomal disorders. Genetic etiologies of developmental microcephalies are reviewed.
真性小头畸形（头围≤ -3标准差），原发性（出生时即存在）或继发性（出生后发病）是由祖细胞生成与细胞死亡之间的失衡导致的，这种失衡会使脑内神经元和神经胶质细胞数量减少，进而导致脑生长减缓。原发性非综合征性小头畸形是祖细胞有丝分裂纺锤体和细胞周期动力学异常控制导致的隐性疾病。小头畸形也是DNA双链和/或单链断裂修复以及核苷酸切除修复缺陷的常见体征，在这些情况中，小头畸形常与全身生长发育障碍相关。在这些病因中，尽管脑容量严重减小，但认知功能仍能得到较好的保留。神经元迁移缺陷常与继发性小头畸形相关，端脑分裂异常也是如此。继发性小头畸形常与神经元死亡增加有关，并且可能与代谢紊乱有关，如丝氨酸缺乏或硫胺素焦磷酸转运体缺乏。小头畸形可与数百种综合征性先天性异常相关，包括许多染色体疾病。本文对发育性小头畸形的遗传病因进行了综述。
