Li et al. (1978, 1981) described a family with ataxia and pancytopenia. The propositus, the youngest of a sibship of 5, had cerebellar ataxia, developed hypoplastic anemia at age 3 years, and died of acute myelomonocytic leukemia at ... Li et al. (1978, 1981) described a family with ataxia and pancytopenia. The propositus, the youngest of a sibship of 5, had cerebellar ataxia, developed hypoplastic anemia at age 3 years, and died of acute myelomonocytic leukemia at age 7. Serial cytogenetic studies of his hypoplastic bone marrow over a 25-month period showed progressive expansion of a clone of cells with monosomy 7 (252270). Cerebellar ataxia was found in the proband's father and all 4 sibs. Two brothers, including 1 with monosomy 7, died with hypoplastic anemia at ages 5 and 9 years, and a third brother died with acute myelocytic leukemia at age 10 years. The only surviving sib at the time of the report of Li et al. (1981) was a 19-year-old sister who had unexplained anemia, decreased mitotic activity in the bone marrow, and a slowly progressive cerebellar ataxia. In addition to progressive cerebellar ataxia, the father had marked progressive cerebellar ataxia, brisk deep tendon reflexes, bilateral Babinski reflexes, and diminished vibratory sensation in the legs. Unsteady gait first brought the father to medical attention at age 28 years and he was not able to work thereafter. Computed tomographic scans of the father, the sister, and 1 brother showed cerebellar atrophy. Autopsy in 1 brother showed marked cerebellar atrophy and loss of 90% of the Purkinje cells; the spinal column was normal. By 1989, the sister had given up her career in nursing because of increasingly severe cerebellar ataxia and the father was largely confined at home (Li, 1989). In a family reported by Daghistani et al. (1989), the proband, a 5-year-old boy, presented with left facial abscess and pancytopenia, following a 2-year history of mild incoordination. He had nystagmus and dysmetria. Monosomy 7 was found. He died at the age of about 6 years from pancytopenia. The sister of the proband, 12 years old at the time of report, had the onset of mild progressive unsteadiness at the age of 7 years. She had nystagmus and dysarthria. Nerve conduction studies showed reduced velocities in both sibs. The mother of the 2 children had had onset of incoordination before age 5. She showed severe gait ataxia and pronounced dysarthria with upper extremity dysmetria and horizontal and vertical nystagmus. Nerve conduction studies showed reduced velocities. The father was normal neurologically and hematologically. None of the 3 patients had oculocutaneous telangiectasia, scoliosis, or cardiac dysfunction. Gonzalez-del Angel et al. (2000) described a Mexican girl who developed cerebellar ataxia at age 3 years and pancytopenia at age 13 years. Cerebral computed tomography scan and magnetic resonance imaging showed evidence of severe cerebellar atrophy. Telangiectasias were not present, and immunoglobulins and alpha-fetoprotein levels were normal, making ataxia-telangiectasia (208900) unlikely. Cytogenetic studies showed no abnormalities except for an increased frequency of chromosomal aberrations in response to bleomycin. The phenotype was considered consistent with the ataxia-pancytopenia syndrome, although monosomy of chromosome 7 was not found in bone marrow. The sensitivity to bleomycin suggested this may be a chromosomal instability disorder. Tsangaris et al. (2008) reported an 18-month-old girl with DKC who presented with pancytopenia and ataxia. Brain imaging showed cerebellar hypoplasia. She later developed a small area of leukoplakia but had no nail dystrophy or skin hyperpigmentation. Laboratory studies showed shortened telomeres and decreased telomerase activity (92.5% reduction compared to control values). The authors emphasized that dyskeratosis congenita (DKC; 127550) is a pleomorphic disorder and that ataxia can be an additional feature found in up to 6.8% of patients (Kirwan and Dokal, 2008). Tsangaris et al. (2008) noted that the combination of ataxia and pancytopenia without other typical features of DKC has been considered a distinct disorder, but concluded that ataxia-pancytopenia is part of the phenotypic spectrum of DKC.
Tsangaris et al. (2008) identified a de novo heterozygous mutation in the TINF2 gene (604319.0002) in an 18-month-old girl who presented with pancytopenia and ataxia. The diagnosis was consistent with dyskeratosis congenita.