Fanconi Anemia Clinical Presentation

During childhood, short stature and skin pigmentation, including café au lait spots, may become apparent. The first sign of a hematologic problem is usually petechiae and bruises, with later onset of pallor, fatigue, and infections.

Because macrocytosis usually precedes thrombocytopenia, patients with typical congenital anomalies associated with Fanconi anemia should at least be evaluated for an elevated erythrocyte mean corpuscular volume. In approximately 35% of patients with Fanconi anemia who were reported to have cancer, the diagnosis of leukemia or a tumor preceded the diagnosis of Fanconi anemia.

About 75% of patients with Fanconi anemia have birth defects, such as altered skin pigmentation and/or café au lait spots (>50%), short stature (50%), thumb or thumb and radial anomalies (40%), abnormal male gonads (30%), microcephaly (25%), eye anomalies (20%), structural renal defects (20%), low birth weight (10%), developmental delay (10%), and abnormal ears or hearing (10%). (See the images below.)

However, literature reports may be biased toward this association, because the clinical diagnosis initially depended on the combination of aplastic anemia and physical anomalies; thus, the frequencies may be overestimated. Patients with biallelic mutations in FANCD1/BRCA2 have a very severe phenotype, including features of the vertebral, anal, cardiac, tracheal, esophageal, and limb (VACTERL) association.^{[1, 8]}

Skin abnormalities in Fanconi anemia can include generalized hyperpigmentation on the trunk, neck, and intertriginous areas, the aforementioned café au lait spots, and hypopigmented areas. Delicate features can also be characteristic of patients.

Upper limb abnormalities can include the following features:

• Thumbs - Absent or hypoplastic, supernumerary, bifid, rudimentary, short, low set, attached by a thread, triphalangeal, tubular, stiff, hyperextensible
• Radii - Absent or hypoplastic (only with abnormal thumbs [ie, terminal defects]), absent or weak pulse
• Hands - Clinodactyly, hypoplastic thenar eminence, 6 fingers, absent first metacarpal, enlarged abnormal fingers, short fingers
• Ulnae - Dysplastic

Gonads may display the following abnormalities:

• Males - Hypogenitalia, undescended testes, hypospadias, abnormal or absent testis, atrophic testes, azoospermia, phimosis, abnormal urethra, micropenis, delayed development
• Females - Hypogenitalia; bicornuate uterus; aplasia of uterus and vagina; atresia of uterus, vagina, or ovary/ovaries

Other skeletal anomalies can include the following features:

• Head and face - Microcephaly, hydrocephalus, micrognathia, peculiar face, bird face, flat head, frontal bossing, scaphocephaly, sloped forehead, choanal atresia
• Neck - Sprengel abnormality, short, low hairline, webbed
• Spine - Spina bifida (thoracic, lumbar, cervical, occult sacral), scoliosis, abnormal ribs, sacrococcygeal sinus, Klippel-Feil syndrome, vertebral anomalies, extra vertebrae
• Feet - Toe syndactyly, abnormal toes, flat feet, short toes, clubfoot, 6 toes
• Legs - Congenital hip dislocation, Perthes disease, coxa vara, abnormal femur, thigh osteoma, abnormal legs

Additional abnormalities found in Fanconi anemia can include the following characteristics:

• Eyes - Small, strabismus, epicanthal folds, hypertelorism, ptosis, slanted, cataracts, astigmatism, blindness, epiphora, nystagmus, proptosis, small iris
• Ears - Deaf (usually conductive), abnormal shape, atresia, dysplasia, low-set, large, small, infections, abnormal middle ear, absent drum, dimples, rotated, canal stenosis
• GI system - High-arch palate, atresia (eg, esophagus, duodenum, jejunum), imperforate anus, tracheoesophageal fistula, Meckel diverticulum, umbilical hernia, hypoplastic uvula, abnormal biliary ducts, megacolon, abdominal diastasis, Budd-Chiari syndrome