43 Fanconi Anemia
Fanconi Anemia 705
FA, Fanconi pancytopenia syndrome
Radial/thumb anomalies, skin hyperpigmentation, renal malformations, pancytopenia, chromosome breakage
Frequency: 1 in 22,000 in South Africa, 1 in 350,000 in North America.
Genetics
Autosomal recessive, genetically heterogeneous; at least nine complementation groups; FANCA (OMIM 607139), gene locus at 16q24.3; FANCB (OMIM 300514), gene locus at Xp22.31; FANCC (OMIM 227645), gene locus at 9q22.3; FANCD1 (OMIM 605724), gene locus at 13q12.3; FANCD2 (OMIM 227647), gene locus at 3p25.3; FANCE (OMIM 600901), gene locus at 6p21–22; FANCF (OMIM 603467), gene locus at 11p15; FANCG (OMIM 602956), gene locus at 9p13; FANCL (OMIM 608111), gene locus at 2p16.1.
Clinical Features
• Low birth weight, short stature
• Microcephaly
• Strabismus, microphthalmia, ptosis of eyelid
• Ear anomalies, deafness
• Heart defects (13%), CNS anomalies (8%)
• Kidney malformation, ectopia, double ureters (35%)
• Cryptorchidism, hypospadias, small penis
• Skin hyperpigmentation, café-au-lait spots (65%)
• Radial hypo/aplasia, thumb hypo/aplasia
• Mental retardation
• Pancytopenia (can be the only symptom)
• Chromosome breakage Differential Diagnosis
• TAR syndrome
• VATER,VACTERL
• Aase-Smith syndrome
• Baller-Gerold syndrome
• Blackfan-Diamond hypoplastic anemia
Radiographic Features Limbs
• Radial ray defect (50% of cases), including absent or hypoplastic thumb, and/or absent or hypoplas- tic radius.
• Supernumerary thumbs in some cases
• Digitalized thumb, bifid thumb
• Hypoplasia or absence of the first metacarpal
• Unusually long navicular bone
• Syndactyly
• Clubfoot, flatfoot
• Genu valgum
• Leg length discrepancy
F
Fig. 43.1. Patient 1, 2nd trimester fetus. Bilateral radial defects and increased spontaneous chromo- some breakage. (Reprinted, with permission, from Mastroiacovo et al. 1990)
Skull
• Microcephaly (25–35%)
• Thickened calvarium Generalized Bone Defects
• Retarded bone age
• Osteoporosis Pelvis
• Hip dislocation Chest
• Sprengel deformity
• Rib anomalies Spine
• Kyphoscoliosis
• Sacral agenesis or hypoplasia
Fanconi Anemia 706
Fig. 43.2. Patient 2, age 7 years. Thumb aplasia on left and severe thumb hypoplasia on right hand. (Reprinted, with per- mission, from Mastroiacovo et al. 1990)
Fig. 43.3 a, b. Patient 3, newborn.
a Unilateral radial ray defect, involving hypoplastic radius, hy- poplastic thumb, curved ulna, and radially deviated hand. b Unaffect- ed contralateral forearm
a b
Bibliography
Auerbach AD, Rogatko A, Schroeder-Kurth TM. International Fanconi Anemia Register: relation of clinical symptoms to diepoxybutane sensitivity. Blood 1989; 73: 391–6
Butturini A, Gale RP, Verlander PC, Adler-Brecher B, Gillio AP, Auerbach AD. Hematologic abnormalities in Fanconi ane- mia: an International Fanconi Anemia Registry study.
Blood 1994; 84: 1650–5
Demirci A, Okten A, Gumele HR. Epiphyseal hypertrophy of first metacarpal simulating pseudoarthrosis in Fanconi’s anemia. Pediatr Radiol 1992; 22: 547
Evans DG, Rees HC, Spreadborough A, Campbell DJ, Gau GS, Pickering E, Hamilton S, Clayton-Smith J. Radial ray de- fects, renal ectopia, duodenal atresia and hydrocephalus:
the extended spectrum for Fanconi anaemia. Clin Dysmor- phol 1994; 3: 200–6
Glanz A, Fraser FC. Spectrum of anomalies in Fanconi anaemia. J Med Genet 1982; 19: 412–6
Gordon-Smith EC, Rutherford TR. Fanconi anemia: constitu- tional aplastic anemia. Semin Hematol 1991; 28: 104–12 Mastroiacovo P, Dallapiccola B,Andria G, Camera G, Lungarot-
ti MS. Difetti congeniti e sindromi malformative. McGraw- Hill, Milan, 1990
Schroeder TM, Tilgen D, Kruger J, Vogel F. Formal genetics of Fanconi’s anemia. Hum Genet 1976; 32: 257–88
Fanconi Anemia 707
F
Fig. 43.4 a, b. Patient 4, newborn.
a Mild radial hypoplasia, severe thumb hypoplasia, and absent 1st metacarpal on right hand. b Both radius and thumb are completely missing on the left hand. Note ra- dial deviation of both hands
a b
