Gonzalez C H, Durkin-Stamm M V, Geimer N F, Shahidi N T, Schilling R F, Rubira F, Opitz J M
Birth Defects Orig Artic Ser. 1977;13(3B):31-8.
We report 2 families with an autosomal dominant syndrome of limb and hematologic abnormalities. The W Family was ascertained through AW, a 13-year-old girl, who was purportedly born without congenital anomalies and who was normal until 11 1/2 years when she developed acute lymphoblastic leukemia. She died 2 years later with CNS involvement. Her chromosomes, studied in the first weeks after diagnosis of the disease, were apparently normal. Her father had clinodactyly of both 5th fingers and was found to have panmyelocytopenia refractory to all treatment at 26 years. He died within a year of the onset of his anemia. This man's oldest brother was born with congenital malformations of the elbows and the hands and was healthy until 38 years when he was also found to have an "idopathic anemia" and panmyelocytopenia which was refractory to treatment except for transfusions; he died at age 42 years. Both men were initially thought to have the Fanconi anemia syndrome. Their mother died at 71 years of leukemia. DT, the propositus of the second family, was noted to have malformations of both hands at birth. At 21 months he had anemia for which he received transfusions. Family history reveals that several people on the paternal side have severe hand anomalies and a history of childhood anemia. The paternal grandfather died at age 51 of acute monocytic leukemia. Barring genetic heterogeneity, we think that the trait in the W and T families in the same. It is a pleiotropic autosomal dominant mutant which affects radial and ulnar development of the upper limbs and is associated with a relatively high risk of transient or permanent bone marrow arrest with or without leukemia. We propose the hypothesis that apparently increased risk of leukemia to Fanconi heterozygotes actually represents admixture with the WT syndrome and that Fanconi heterozygotes may not have an increased risk of leukemia.
我们报告了2个患肢体与血液学异常常染色体显性综合征的家族。W家族通过一名13岁女孩AW确诊，据称她出生时无先天性异常，11岁半前一切正常，之后患上急性淋巴细胞白血病。2年后她因中枢神经系统受累而死亡。在疾病诊断后的头几周对她的染色体进行研究，结果显然正常。她的父亲双手第5指均有 clinodactyly（临床术语，可能是指手指弯曲等畸形，此处未明确中文对应词），26岁时被发现患有对所有治疗均无效的全血细胞减少症。他在贫血发作后一年内死亡。这名男子的大哥出生时肘部和手部有先天性畸形，38岁前一直健康，之后也被发现患有“特发性贫血”和全血细胞减少症，除输血外治疗无效；他42岁时去世。这两名男子最初都被认为患有范可尼贫血综合征。他们的母亲71岁时死于白血病。第二个家族的先证者DT出生时被发现双手有畸形。21个月大时他出现贫血并接受了输血治疗。家族史显示，父系的几个人有严重的手部异常和儿童期贫血病史。祖父51岁时死于急性单核细胞白血病。排除遗传异质性因素，我们认为W家族和T家族的特征相同。这是一种多效性常染色体显性突变，影响上肢桡骨和尺骨发育，与有或无白血病的短暂或永久性骨髓抑制的相对高风险相关。我们提出一个假说，即范可尼杂合子白血病风险明显增加实际上代表了与WT综合征的混合，并且范可尼杂合子可能没有增加的白血病风险。
