California Pacific Medical Center and San Francisco General Hospital, School of Medicine, University of California San Francisco, San Francisco, California, USA.
Am J Med Genet A. 2010 Oct;152A(10):2634-9. doi: 10.1002/ajmg.a.33651.
Karyotypic discordance between different tissues in an individual is uncommon. We report on a patient with multiple congenital anomalies and mosaicism for monosomy 13 limited to fibroblasts. Findings include microcephaly, agenesis of the corpus callosum, bilateral posterior colobomas, cataract and optic nerve dysplasia, patent foramen ovale, renal hypoplasia, hypospadias and unilateral inguinal hernia, unilateral hypoplasia of the lower limb, sparse and patchy hair, subtle pigmentary mosaicism, and global developmental delay. The lymphocyte karyotype was normal, whereas the fibroblast karyotype showed mosaicism for a del(13)(q11→ter). Review of the literature identified three previous reports of similar patients with multiple congenital anomalies, normal lymphocyte karyotype, and subsequent, diagnostic fibroblast karyotyping. Comparison of the previously reported patients with the patient reported here defines a common phenotype for tissue-limited mosaicism for monosomy 13 consisting of prenatal-onset growth deficiency; microcephaly; facial abnormalities including prominent nasal bridge, hypertelorism, ptosis, epicanthal folds, microphthalmia, coloboma, retinoblastoma, prominent maxilla, micrognathia, and low-set ears; limb abnormalities including small to absent thumbs, clinodactyly of fifth finger, fused metacarpal bones 4 and 5, talipes equinovarus, and short first toe; cardiac defect; renal anomalies; and genitalia abnormalities including hypospadias and cryptorchidism. In conclusion, this case further emphasizes that fibroblast karyotyping should be employed when the diagnosis remains unclear, especially in the presence of pigmentary mosaicism or segmental hypoplasia.
个体不同组织之间的核型不一致较为罕见。我们报告了一例多发性先天畸形患者，其存在局限于成纤维细胞的单体 13 号染色体单体性嵌合体。发现的异常包括小头畸形、胼胝体发育不全、双侧后颅窝脑裂畸形、白内障和视神经发育不良、卵圆孔未闭、肾发育不全、尿道下裂和单侧腹股沟疝、单侧下肢发育不良、稀疏和斑片状毛发、轻微色素镶嵌性、以及全面发育迟缓。淋巴细胞核型正常，而成纤维细胞核型显示单体性 13 号染色体缺失（q11→ter）嵌合体。文献复习发现了三例先前报道的类似患者，他们具有多发性先天畸形、正常的淋巴细胞核型，随后进行了诊断性成纤维细胞核型分析。将先前报道的患者与本报告患者进行比较，确定了局限于单体性 13 号染色体的成纤维细胞嵌合体的共同表型，包括产前起病的生长发育迟缓；小头畸形；面部异常，包括高鼻梁、眼距过宽、上睑下垂、内眦赘皮、小眼球、脑裂畸形、视网膜母细胞瘤、上颌突出、小下颌、低位耳；肢体异常，包括小拇指缺失或发育不全、第五指弯曲、第 4 和第 5 掌骨融合、马蹄内翻足、第一趾短；心脏缺陷；肾脏异常；以及生殖器异常，包括尿道下裂和隐睾。总之，本例进一步强调了在诊断仍不明确时，尤其是存在色素镶嵌性或节段性发育不良时，应进行成纤维细胞核型分析。
