The most common physical features of the IBMFSs organized by typical first presenting cytopenia
| Physical feature . | Macrocytosis . | . | |||||
|---|---|---|---|---|---|---|---|
| Thrombocytopenia . | Anemia . | Neutropenia . | |||||
| TAR . | TBD* . | FA* . | DBA . | SDS . | GATA2 deficiency . | SCN* . | |
| Head and neck | Oral leukoplakia,† early gray hair, ophthalmic anomalies | Microcephaly, hearing loss/ear anomalies, ophthalmic anomalies/small eyes | Craniofacial defects, short/webbed neck | Hearing loss | Hearing loss, dental carries, gingivitis | ||
| Pulmonary | Pulmonary fibrosis, emphysema | Pulmonary dysfunction, PAP | |||||
| Cardiovascular | Septal defects | Congenital heart defects | |||||
| Gastrointestinal | Liver cirrhosis, hepatopulmonary syndrome, esophageal strictures | Tracheoesophageal fistula, esophageal atresia | Pancreatic dysfunction | ||||
| Genitourinary/ gynecologic | Urethral strictures | Renal/GU tract anomalies, infertility | Renal/GU tract anomalies | GU tract anomalies, preterm labor | |||
| Musculoskeletal | Absent radii with thumbs present‡ | Short stature, avascular necrosis, osteoporosis | Short stature, thumb/radii anomalies‡ | Short stature, thumb anomalies | Short stature, metaphyseal dysostosis | Bone mineral loss | |
| Dermatologic | Lacy reticulated skin pigmentation,* dysplastic nails* | Cafe au lait spots, hypo-/hyperpigmentation | Eczema | HPV-related warts, panniculitis | Eczema | ||
| Vascular | Arteriovascular malformations | Lymphedema, DVT/PE | |||||
| Immunologic | Variable immunodeficiency | Recurrent infections | Mycobacterial, fungal, viral infections, autoimmune disease | Recurrent infections | |||
| CNS/neurologic | Developmental delay, cerebellar hypoplasia | Developmental delay, learning disabilities, hypopituitarism | Developmental delay | Developmental delay, learning disabilities | Behavioral disorders | Developmental delay, epilepsy | |
| Malignancy | MDS/AML | MDS/AML, SCC anogenital region, SCC head and neck, SCC and basal cell skin cancer | MDS/AML, SCC anogenital region, SCC head and neck, SCC and basal cell skin cancer | MDS/AML, GI tract malignancies, osteogenic sarcoma | MDS/AML | MDS/AML, SCC anogenital region, SCC and basal cell skin cancer | MDS/AML |
| Physical feature . | Macrocytosis . | . | |||||
|---|---|---|---|---|---|---|---|
| Thrombocytopenia . | Anemia . | Neutropenia . | |||||
| TAR . | TBD* . | FA* . | DBA . | SDS . | GATA2 deficiency . | SCN* . | |
| Head and neck | Oral leukoplakia,† early gray hair, ophthalmic anomalies | Microcephaly, hearing loss/ear anomalies, ophthalmic anomalies/small eyes | Craniofacial defects, short/webbed neck | Hearing loss | Hearing loss, dental carries, gingivitis | ||
| Pulmonary | Pulmonary fibrosis, emphysema | Pulmonary dysfunction, PAP | |||||
| Cardiovascular | Septal defects | Congenital heart defects | |||||
| Gastrointestinal | Liver cirrhosis, hepatopulmonary syndrome, esophageal strictures | Tracheoesophageal fistula, esophageal atresia | Pancreatic dysfunction | ||||
| Genitourinary/ gynecologic | Urethral strictures | Renal/GU tract anomalies, infertility | Renal/GU tract anomalies | GU tract anomalies, preterm labor | |||
| Musculoskeletal | Absent radii with thumbs present‡ | Short stature, avascular necrosis, osteoporosis | Short stature, thumb/radii anomalies‡ | Short stature, thumb anomalies | Short stature, metaphyseal dysostosis | Bone mineral loss | |
| Dermatologic | Lacy reticulated skin pigmentation,* dysplastic nails* | Cafe au lait spots, hypo-/hyperpigmentation | Eczema | HPV-related warts, panniculitis | Eczema | ||
| Vascular | Arteriovascular malformations | Lymphedema, DVT/PE | |||||
| Immunologic | Variable immunodeficiency | Recurrent infections | Mycobacterial, fungal, viral infections, autoimmune disease | Recurrent infections | |||
| CNS/neurologic | Developmental delay, cerebellar hypoplasia | Developmental delay, learning disabilities, hypopituitarism | Developmental delay | Developmental delay, learning disabilities | Behavioral disorders | Developmental delay, epilepsy | |
| Malignancy | MDS/AML | MDS/AML, SCC anogenital region, SCC head and neck, SCC and basal cell skin cancer | MDS/AML, SCC anogenital region, SCC head and neck, SCC and basal cell skin cancer | MDS/AML, GI tract malignancies, osteogenic sarcoma | MDS/AML | MDS/AML, SCC anogenital region, SCC and basal cell skin cancer | MDS/AML |
This table provides an overview of the most common features (in bold); see detailed reviews for additional features.4,5,7,8,18,20,27-29,31,32,36,37,41,49
DBA, Diamond-Blackfan anemia; DVT/PE, deep vein thrombosis/pulmonary embolism; FA, Fanconi anemia; GI, gastrointestinal; GU, genitourinary; HPV, human papillomavirus; MDS/AML, myelodysplastic syndrome/acute myeloid leukemia; PAP, pulmonary alveolar proteinosis; SCC, squamous cell carcinoma; SCN, severe congenital neutropenia; SDS, Shwachman-Diamond syndrome; TAR, thrombocytopenia absent radii; TBD, telomere biology disorder.
Syndromic features and their severity vary by the specific gene involved.
Diagnostic triad seen in the classical TBD presentations; these features may be variably present or even absent in patients with known TBD. Adult onset forms often feature pulmonary fibrosis and cytopenias as predominant features.
In FA, if the radius is absent, the thumb is absent, whereas in TAR, bilateral radii are often absent with thumbs present.