Johnson-Tesch Benjamin A, Gawande Rakhee S, Zhang Lei, MacMillan Margaret L, Nascene David R
Department of Radiology, University of Minnesota, MMC 292, 420 Delaware St. SE, Minneapolis, MN, 55455, USA.
Department of Radiology, Neuroradiology Section, University of Minnesota, Minneapolis, MN, USA.
Pediatr Radiol. 2017 Jun;47(7):868-876. doi: 10.1007/s00247-017-3817-x. Epub 2017 Mar 10.
Congenital central nervous system abnormalities in children with Fanconi anemia are poorly characterized, especially with regard to specific genetic complementation groups.
To characterize the impact of genetic complementation groups on central nervous system anatomy.
Through chart review we identified 36 patients with Fanconi anemia with available brain MRIs at the University of Minnesota (average age, 11.3 years; range, 1-43 years; M:F=19:17), which we reviewed and compared to 19 age- and sex-matched controls (average age, 7.9 years; range, 2-18 years; M:F=9:10). Genotypic information was available for 27 patients (15 FA-A, 2 FA-C, 3 FA-G, and 7 FA-D1 [biallelic mutations in BRCA2 gene]).
Of the 36 patients, 61% had at least one congenital central nervous system or skull base abnormality. These included hypoplastic clivus (n=12), hypoplastic adenohypophysis (n=11), platybasia (n=8), pontocerebellar hypoplasia (n=7), isolated pontine hypoplasia (n=4), isolated vermis hypoplasia (n=3), and ectopic neurohypophysis (n=6). Average pituitary volume was significantly less in patients with Fanconi anemia (P<0.0001) than in controls. Basal angle was significantly greater in Fanconi anemia patients (P=0.006), but the basal angle of those with FA-D1 was not significantly different from controls (P=0.239). Clivus length was less in the Fanconi anemia group (P=0.002), but significance was only observed in the FA-D1 subgroup (P<0.0001). Of the seven patients meeting criteria for pontocerebellar hypoplasia, six belonged to the FA-D1 group.
Patients with Fanconi anemia have higher incidences of ectopic neurohypophysis, adenohypophysis hypoplasia, platybasia and other midline central nervous system skull base posterior fossa abnormalities than age- and sex-matched controls. Patients with posterior fossa abnormalities, including pontocerebellar hypoplasia, are more likely to have biallelic BRCA2 mutations.
范可尼贫血患儿的先天性中枢神经系统异常特征尚不明确，尤其是在特定基因互补组方面。
明确基因互补组对中枢神经系统解剖结构的影响。
通过查阅病历，我们在明尼苏达大学确定了36例有可用脑部MRI的范可尼贫血患者（平均年龄11.3岁；范围1 - 43岁；男:女 = 19:17），并对其进行了回顾，且与19例年龄和性别匹配的对照者（平均年龄7.9岁；范围2 - 18岁；男:女 = 9:10）进行了比较。27例患者有基因分型信息（15例FA - A型，2例FA - C型，3例FA - G型，7例FA - D1型[BRCA2基因双等位基因突变]）。
36例患者中，61%至少有一项先天性中枢神经系统或颅底异常。这些异常包括斜坡发育不全（n = 12）、腺垂体发育不全（n = 11）、扁平颅底（n = 8）、脑桥小脑发育不全（n = 7）、孤立性脑桥发育不全（n = 4）、孤立性小脑蚓部发育不全（n = 3）以及异位神经垂体（n = 6）。范可尼贫血患者的垂体平均体积显著小于对照组（P < 0.0001）。范可尼贫血患者的基底角显著增大（P = 0.006），但FA - D1型患者的基底角与对照组无显著差异（P = 0.239）。范可尼贫血组的斜坡长度较短（P = 0.002），但仅在FA - D1亚组中观察到显著性差异（P < 0.0001）。在符合脑桥小脑发育不全标准的7例患者中，6例属于FA - D1组。
与年龄和性别匹配的对照组相比，范可尼贫血患者发生异位神经垂体、腺垂体发育不全、扁平颅底及其他中线中枢神经系统颅底后颅窝异常的发生率更高。患有包括脑桥小脑发育不全在内的后颅窝异常的患者更可能有BRCA2基因双等位基因突变。
