Table 1.
Systems involved in patients with an IBMFS
| System | FA | DC | DBA | SDS |
|---|---|---|---|---|
| Hematology | Aplastic anemia, MDS, AML | Aplastic anemia, MDS, AML, lymphomas | Anemia, MDS, AML | Neutropenia, aplastic anemia, MDS, AML |
| Oncology | Head and neck SCC (tongue), vulvar SCC, esophagus, brain, skin | Head and neck SCC (tongue), anogenital SCC, stomach, lung, esophagus, skin | Colon, lung, osteosarcoma, gynecologic, stomach | Ovarian cancer |
| Perinatal | Low birth weight, intrauterine growth retardation | Low birth weight, intrauterine growth retardation | Low birth weight, hydrops | Low birth weight |
| Skin | Café au lait spots, basal cell, and SCC | Lacy reticulated pigmentation, dystrophic nails (soft, brittle, ridged, disappearing), adermatoglyphia, hyperhidrosis, basal cell, and SCCs | — | Ichthyosis, eczema |
| Skeletal | Absent or abnormal thumbs, absent or hypoplastic radius; flat thenar eminence; Klippel Feil, congenital hip dislocation | Avascular necrosis hips or shoulders, osteoporosis, scoliosis, spontaneous fractures | Thumbs triphalangeal, bifid, duplicated, subluxed, extra, hypoplastic; web neck, Sprengel, Klippel-Feil, short neck; scoliosis | Metaphyseal dysostosis; small thorax, narrow chest, pectus carinatum; dysplastic hips, bow legs, short legs, Legg Calve Perthes; short neck; scoliosis; flared ribs; osteopenia |
| Eyes | Microphthalmia, microcornea, ptosis, epicanthal folds, strabismus, cataracts | Epiphora (from lacrimal duct stenosis), blepharitis, exudative retinopathy, retinal neovascularization, retinal hemorrhages, entropion, ectropion, cataracts | Small, epicanthal folds, hypertelorism, hypotelorism, strabismus, cataract, glaucoma | Hypertelorism, retinitis pigmentosum, esotropia |
| Kidney | Ectopic, horseshoe, absent, small, hydronephrosis, hydroureter | — | Horseshoe, duplicated, ectopic, absent | — |
| Gonads, male | Small testes, infertility, undescended, micropenis | Urethral stricture, phimosis, small testes, undescended testes, meatal stenosis, hypospadias | Undescended testes, hypospadias, inguinal hernia | Atrophic testes, hypospadias |
| Gonads, female | Small ovaries, bicornuate uterus, late menarche, early menopause, premature ovarian failure, vulvar cancer, breast cancer | Hymenal and urethral stricture | — | — |
| Pregnancies | Decreased blood counts, fetal loss, pre-eclampsia, failure of labor to progress, cesarean sections, small babies | No apparent problems | Worsening of anemia, fetal loss, pre-eclampsia, intrauterine growth retardation, preterm deliveries, fetal malformations, placental infarcts | — |
| Development | Developmental delay, retardation | Developmental delay, retardation | Developmental delay, retardation | Developmental delay, neurocognitive deficits, attention deficit |
| Otology | Abnormal pinna, narrow canal, conductive or sensory hearing loss | Deaf rare | Low set, small, deaf | Decreased hearing |
| Cardiology | Congenital heart disease, iron overload | Hyperlipidemia | Congenital heart disease, iron overload | Congenital heart disease |
| Endocrine | Short, diabetes, metabolic syndrome, growth hormone deficiency, osteoporosis, hypothyroid, delayed bone age | Short, bone problems (see skeletal), hypogonadism, elevated cholesterol (on androgens) | Short | Short |
| Gastroenterology | Imperforate anus, TE fistula, esophageal/duodenal atresia, annular pancreas, gastric emptying delay, poor weight gain, poor feeding, esophageal SCC | Esophageal stenosis, telangiectasias, varices, ulcers, enteropathy (small bowel), enterocolitis (colon), rectal adenocarcinoma | Stomach and colon cancer | Malabsorption due to exocrine pancreatic insufficiency; diarrhea; inguinal hernia |
| Liver | Cirrhosis, fibrosis, elevated enzymes, iron overload, androgen toxicity, adenoma, hepatocellular carcinoma, peliosis hepatis | Cirrhosis, fibrosis, hepatocellular carcinoma, hepatopulmonary syndrome, portal hypertension, iron overload | Iron overload, hepatocellular carcinoma | Rare hepatomegaly |
| Head | Microcephaly | Microcephaly | Microcephaly, hydrocephalus; cleft palate, cleft lip | Microcephaly, macrocephaly, hydrocephaly; cleft palate, cleft lip |
| Brain | Pituitary stalk interruption, small pituitary, hypopituitarism, absent corpus callosum, cerebellar hypoplasia | Cerebellar hypoplasia, intracranial calcifications | Hypopituitary, Chiari, myelomeningocele | Chiari, cerebellar tonsillar ectopia, hypopituitarism |
| Dental | Poor hygiene, abnormal tooth development, oral ulcers, gum infections, oral SCC | Caries, tooth loss, periodontitis, taurodontism (enlarged pulp chamber), decreased root/crown ratio, leukoplakia, tongue cancer, lichen planus | — | Caries, oral ulcers |
| ENT | Head and neck SCC (oral, pharyngeal, hypopharyngeal, laryngeal) | Head and neck SCC | — | — |
| Immunology | Decreased immunoglobulins, some lymphocyte deficiencies with age | Immunodeficiency of immunoglobulins or lymphopenia in younger children | Essentially normal | Some B- and T-cell deficiencies |
| Lung | — | Pulmonary fibrosis, pulmonary arteriovenous malformations | — | — |
| Hair | — | Early gray, early hair loss, sparse eyebrows and eyelashes | — | — |
| Vascular complications | — | Telangiectases and arteriovenous malformations (retinal, GI, pulmonary) | — | — |
| Psychiatry | Some psychiatric problems | |||
| Diagnostic screening test | Increased chromosome breakage with DEB or MMC | Decreased telomere length by flow FISH | Increased red cell adenosine deaminase | Decreased pancreatic enzymes (trypsinogen, isoamylase) |