Syndrome
Upper limb anomaly
Commonly associated features
Inheritance pattern
Testing
Cornelia de Lange
Absent or hypoplastic ulna; oligodactyly
Prenatal growth retardation, microcephaly, congenital heart disease (CHD), dysmorphic features, GU anomalies
Autosomal dominant, mostly de novo
Molecular
Fanconi anemia
Radial ray deficiencies
Short stature, microcephaly, pancytopenia
Autosomal recessive, X-linked
Chromosome breakage, molecular
Poland anomaly
Distal transverse defect, unilateral symbrachydactyly
Ipsilateral pectoral muscle deficiency (Fig. 1), cranial nerve palsy
Sporadic (most) or autosomal dominant
Unknown
Holt-Oram
Radial, thenar, or carpal bone malformation
CHD (esp. ASD/VSD), cardiac conduction defects
Autosomal dominant
Molecular
Thrombocytopenia-absent radius (TAR)
Thrombocytopenia, other skeletal anomalies, GU anomalies
Autosomal recessive (deletion or mutation)
Deletion in 1q21.1; molecular
Roberts
Mesomelic shortening leading to hypomelia, symmetric tetraphocomelia, oligodactyly, syndactyly, clinodactyly
Prenatal growth retardation, cleft lip +/− palate, dysmorphic facies, intellectual disability
Autosomal recessive
Premature centromere separation, Molecular
Adams-Oliver
Terminal transverse limb defects, syndactyly, brachydactyly
CHD, cutis aplasia (absence of a portion of skin, usually on the scalp) (Fig. 4)
Autosomal dominant or recessive
Molecular
Amniotic band sequence
Amputation of digits and/or limbs, constriction bands (Fig. 5)
Cleft lip +/− palate, club foot
Sporadic
Disruption
Nager
Radial ray deficiency
Cleft lip +/− palate, micrognathia, dysmorphic features
Autosomal dominant
Molecular
Thalidomide exposure
Variable long bone deficiencies, oligodactyly
Ear anomalies, CHD
Teratogen
N/A
VACTERL
Radial aplasia proximally placed thumb, humeral hypoplasia
Vertebral anomalies, anal atresia, CHD, tracheoesophageal fistula, renal anomalies
Sporadic (most), autosomal dominant, or X-linked
Unknown
Synostosis /Syndactyly
Synostosis is an osseous connection between bones that are typically separate and is usually due to the failure of complete segmentation of cartilaginous template of the skeleton. Symphalangism is defined as synostosis of phalanges resulting from failure of development of interphalangeal joints. Syndactyly is due to a failure of the digits to separate during weeks 6–8 in embryonic development and may involve the bone and nails or only soft tissue. Syndactyly is the most common congenital anomaly of the limbs, occurring in 2/1,000–3/1,000 live births (Schwabe and Mundlos 2004; Table 2).
Table 2
Selected syndromes with synostosis and/or syndactyly as a common feature
Syndrome | Upper limb anomaly | Commonly/variably associated features | Inheritance pattern | Testing |
|---|---|---|---|---|
Apert | Cutaneous and/or osseous syndactyly (Fig. 6) | Craniosynostosis, shallow orbits with hypertelorism (Fig. 7), hearing loss, cleft palate | Autosomal dominant | Molecular |
Adams-Oliver | Terminal transverse limb defects, syndactyly, brachydactyly | CHD, cutis aplasia | Autosomal dominant or recessive | Molecular |
Fibrodysplasia ossificans progressiva | Synostosis, broad thumbs | Progressive ossification of soft tissue, hearing loss, broad great toes | Autosomal dominant | Molecular |
Pfeiffer | Syndactyly, broad thumbs, radiohumeral synostosis | Craniosynostosis, broad great toes, hydrocephalus, occasional mental retardation | Autosomal dominant | Molecular |
Timothy | Unilateral or bilateral cutaneous syndactyly involving fingers two to five | Prolonged QT interval, CHD, hypertrophic cardiomyopathy, seizures, intellectual disability | Autosomal dominant | Molecular |
Polydactyly
Polydactyly occurs from excessive partitioning of the hands and feet resulting in complete or incomplete extra digits. Postaxial polydactyly describes an extra digit on the ulnar side and preaxial polydactyly is accessory digits on the radial side. Isolated postaxial polydactyly is common in the African-American population (Frazier 1960), and postaxial polydactyly in this population is therefore less likely to be associated with a syndrome. Mesoaxial or central polydactyly is the partial or complete duplication on the 2nd, 3rd, or 4th finger (Table 3).
Table 3
Selected syndromes with polydactyly as a common feature
Syndrome | Upper limb anomaly | Commonly associated features | Inheritance pattern | Testing |
|---|---|---|---|---|
Bardet-Biedl | Postaxial polydactyly | Truncal obesity, renal anomalies, retinal dystrophy, mental retardation | Autosomal recessive | Molecular |
Meckel-Gruber | Postaxial polydactyly | Encephalocele, cystic kidneys, cleft lip+/− palate hepatic fibrosis | Autosomal recessive | Molecular |
Trisomy 13 | Postaxial polydactyly | Holoprosencephaly, midline cleft lip+/−palate, intellectual disability | Chromosomal | Karyotype |
Oral-facial-digital syndrome, type 1 | Preaxial or postaxial polydactyly, syndactyly, clinodactyly, brachydactyly | Bifid or trifid tongue, cleft palate, brain anomalies, renal cysts, duplicated hallux | X-linked dominant | Molecular |
McKusick-Kaufman | Postaxial polydactyly, mesoaxial polydactyly | CHD, GU malformations | Autosomal recessive | Molecular |
Short rib-polydactyly syndromes (types I–V) | Postaxial polydactyly | Lethal skeletal dysplasia (short limbs, short ribs), CHD, polycystic kidneys | Autosomal recessive | Molecular (types II, III, and V) |
Simpson-Golabi-Behmel | Postaxial polydactyly, brachydactyly, cutaneous syndactyly | Pre and postnatal macrosomia, organomegaly, large mouth, CHD, prolonged QT, | X-linked | Molecular |
Pallister-Hall | Postaxial polydactyly, mesoaxial polydactyly | Hypothalamic hamartoma, bifid epiglottis | Autosomal dominant | Molecular |
Fanconi anemia | Preaxial polydactyly, hypoplastic, or absent thumbs/radius | Microcephaly, short stature, pancytopenia/bone marrow failure | Autosomal recessive or X-linked | Chromosome breakage studies, molecular |
Townes-Brocks | Preaxial polydactyly, triphalangeal thumbs | Imperforate anus, preauricular pits/tags, sensorineural deafness, renal agenesis/impairment | Autosomal dominant | Molecular |
Carpenter | Postaxial polydactyly, brachydactyly, clinodactyly, syndactyly, camptodactyly | Craniosynostosis, CHD, growth and intellectual disability | Autosomal recessive | Molecular |
Ellis-van Creveld | Postaxial or mesoaxial polydactyly, nail dysplasia (Fig. 8) | Short-limb dwarfism, neonatal teeth, narrow chest | Autosomal recessive | Molecular |
Brachydactyly
Brachydactyly refers to shortening of the digits and can be due to underdeveloped, absent, or abnormally shaped phalanges or metacarpals. Single or multiple digits may be involved and shortening can be symmetric or asymmetric. Types of brachydactyly are classified by the clinical and radiographic patterns of involvement of the digits (Temtamy and McKusick 1978). Important syndromes with brachydactyly are included here for completeness although if brachydactyly is the only orthopedic anomaly, a child is not likely to be referred to orthopedic surgery. However, brachydactyly is likely to be noticed in a complete orthopedic examination and might be an important clue to an undiagnosed genetic syndrome (Table 4).
Table 4
Selected syndromes with brachydactyly
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