Table I.
Clinical Features of 16 Patients With Fanconi Anemia Due to FANCI Mutations
| Patient ID, sex, (reference) | VACTERL features | FA features | Hematologic findings, age | Status | FANCI mutation(s) |
|---|---|---|---|---|---|
| EUFA592, F, Dorsman et al. [2007]; Levitus et al. [2004] | Thumb/radius, kidney, cardiac | Growth retardation | BMF, 2.5 yrs | Died at 6.5 yrs from aplastic anemia | p.Met1?, homozygous |
| BD952, F, sibling of 1428, Dorsman et al [2007]; Levitus et al [2004] | None reported | Growth retardation | BMF, 8 yrs | Died at 23 yrs | p.Arg1285Gln, homozygous |
| 1428, M, sibling BD952, Dorsman et al. [2007] | None reported | Growth retardation | BMF, 7.3 yrs | Died at 15 yrs | p.Arg1285Gln, homozygous |
| EUFA695, M Dorsman et al. [2007] | None reported | NR | NR | NR | p.Arg964_Gln1002del and p.Gly422Arg |
| EUFA816, M, sibling of EUFA480, Dorsman et al. [2007]; Levitus et al. [2004] | None reported | Growth retardation | BMF, 6 yrs | Died at 12 yrs, after HSCT | p.Arg1285X and p.Glu1117fs |
| EUFA480, M, sibling of EUFA816, Dorsman et al. [2007]; Sims et al. [2007] | None reported | Growth retardation | BMF, 4.8 yrs | HSCT at 8.5 yrs, alive at 24 yrs | p.Arg1285X and p.Glu1117fs |
| EUFA961, M, Dorsman et al. [2007]; Levitus et al. [2004] | Thumb/radius, kidney, cardiac | Growth retardation | BMF, 8 yrs | Died at age 21 yrs after HSCT | p.Glu1117fs and p.His858_Arg879del |
| EUFA1399, M, Dorsman et al. [2007] | Thumb/radius, kidney, cardiac | Growth retardation | BMF, 1 yr | Alive at 30.5 yrs | p.Arg1299X, homozygous |
| F010191, NR, [Sims et al. [2007] | Thumb/radius | Growth retardation, microphthalmia, hearing loss | Anemia, 1 yr, transfusion dependent | Alive at 31 yrs | p.Arg614X and p.Arg1299X |
| F010095, NR, Sims et al. [2007] | Thumb, kidney | Growth retardation, microphthalmia, multiple congenital malformations including hearing loss | BMF, 6 yrs | Died at 21 yrs during HSCT | p.His858Tyr and His1146LeufsX12 |
| IFAR663, Sims et al. [2007] | Thumb, kidney, cardiac | Growth retardation, microphthalmia, multiple congenital malformations including brain, and hearing loss | HSCT at 6 years | Alive at 10 yrs | p.Glu837X and p.Asp1301GlyfsX3 |
| Case 6, F, Scheckenbach et al. [2012] | None reported | None | Anemia and thrombocyto‐penia, treated with danazol starting at age 12 for at least 3 yrs | Alive at 15 yrs | p.Arg1285Gly, homozygous |
| FA14, NR, Chandrasekharappa et al. [2013] | NR | NR | NR | p.Gly422Arg and intron 16 variant (c.1583+142C>T) | |
| NCI‐82‐1, F, Current report | Bilateral absent thumbs, short right radius, fusion of C5‐C6 vertebral bodies, ASD, VSD, duodenal atresiaa, small kidneys | Fanconi facies, short stature, microphthalmia, microcephaly, hearing impaired, right ear canal atresia, septo‐optic dysplasia, small pituitary, absent septum pellucidum, café au lait macules, normal vision, pale optic disk, hypoplastic optic nerves, central hypothyroid, GH deficiency, mild developmental delay. Mother age 30 yrs at birth. | Diagnosed at birth, severe BMF, HSCT at 10.5 yrs | Died at 11.5 yrs, from HSCT complications | p.Ser1268Argfs*5 and p.Asp1301Glyfs*3 |
| NCI‐253‐1, F, Current report | Abnormal cervical vertebra, dangling left thumb, VSD, PFO, horseshoe kidney | Premature with intrauterine growth retardation. Triangular facies, short stature, microcephaly, microphthalmia, narrow ear canals, abnormal middle ear bones, colpocephaly, abnormal corpus callosum, developmental delay, café au lait macules, myopia, astigmatism, normal optic disks, primary hypothyroidism, mild developmental delay. GH not measured. Mother age 32 yrs at birth. | Diagnosed at 5 mo. At age 3 yrs: normal white blood count, hemoglobin, and platelets. HbF 6.3%, bone marrow cellularity 40% at 5 yrs | Alive at 6 yrs | p.Tyr487X and p.Cys1014Tyr |
| NCI‐309‐1, F, Current report | Hypoplastic thumbs, short neck with narrow C5 vertebra, VSD, ASD, PDA, grade 3 vesicoureteral reflux requiring ureter re‐implantation | Short left first metacarpal, microcephaly, microophthalmia, triangular facies, chiari malformation, small anterior pituitary gland with poorly visible stalk, mild bilateral conductive hearing loss; normal optic discs, optic nerves, and vision. Normal endocrine function, normal development. Mother age 32 yrs at birth. | Diagnosed at birth. At age 8 yrs: mild neutropenia, normal hemoglobin and platelets. Bone marrow cellularity 20–50% | Alive at 9 yrs | p.Ser347Pro and p.Gly401Glufs |
F, female; M, male; NR, not reported; yrs, years of age; mo, months; BMF, bone marrow failure; HSCT, hematopoietic stem cell transplantation; CBC, complete blood count; HbF, hemoglobin F; ASD, atrial septal defect; VSD, ventricular septal defect; PFO, patent foramen ovale; GH, growth hormone. Patient characteristics and identifiers (ID) are derived from the referenced publications. Mutation nomenclature is written as reported in each publication. The data may not be directly comparable because of variability between centers and data reported in each publication. VACTERL denotes an inference of the VACTERL association based on information reported in the published report.
a
Duodenal atresia is considered to be part of the VACTERL association by some reports [Solomon et al., 2010].