What genetic syndromes are associated with abnormalities of the fifth digit of the hand?

Genetic Syndromes Associated with Fifth Digit Abnormalities of the Hand

Several genetic syndromes are characterized by abnormalities of the fifth digit of the hand, including clinodactyly, brachymesophalangia, and polydactyly.

Common Genetic Syndromes with Fifth Digit Abnormalities

Down Syndrome (Trisomy 21)

• Characterized by fifth finger clinodactyly (curved fifth finger) and brachymesophalangia (shortened middle phalanx) 1
• Hand development studies show reduced length of individual bones in the third finger during fetal development 1
• The middle phalanx of the fifth finger often appears later than normal or may not appear at all in some cases 1

Williams Syndrome

• Caused by a chromosome microdeletion at 7q11.23 (incorporating the elastin gene) 2
• Features include distinctive facial appearance ("elfin facies"), mild-to-moderate developmental delay, cardiovascular abnormalities (particularly supravalvular aortic stenosis) 2
• Hand anomalies can include fifth finger clinodactyly 2

22q11.2 Deletion Syndrome (DiGeorge/Velocardiofacial Syndrome)

• Characterized by thymic and parathyroid hypoplasia, immunodeficiency, low-set ears, and cardiac defects 2
• Hand abnormalities may include fifth finger clinodactyly 2
• Associated with conotruncal heart defects including tetralogy of Fallot, interrupted aortic arch type B, and truncus arteriosus 2

Simpson-Golabi-Behmel Syndrome (SGBS)

• X-linked condition caused by mutations in GPC3 or GPC4 genes 2
• Features include pre- and postnatal macrosomia, distinctive craniofacial features, macrostomia, and macroglossia 2
• Hand anomalies include large hands and postaxial polydactyly (extra digit on the ulnar/little finger side) 2

Noonan Syndrome

• Caused by mutations in PTPN11, KRAS, SOS1, RAF1, NRAS, BRAF, or MAP2K1 genes 2
• Features include facial anomalies, webbed neck, chest deformity, short stature, and cardiac defects (particularly pulmonary stenosis) 2
• Fifth finger clinodactyly may be present 3

Less Common Syndromes with Fifth Digit Abnormalities

Fetal Alcohol Syndrome

• Caused by maternal alcohol consumption during pregnancy 2
• Features include growth deficiency, characteristic facial features, and central nervous system abnormalities 2
• Fifth finger clinodactyly is among the minor anomalies that may be present 2

Autosomal Dominant Syndrome with Tetralogy of Fallot

• Characterized by mild prenatal-onset growth deficiency, distinctive facial appearance, preauricular pits, and fifth finger clinodactyly 3
• Tetralogy of Fallot is present in some affected individuals 3
• Shows autosomal dominant inheritance with male-to-male transmission 3

Types of Fifth Digit Abnormalities

Clinodactyly

• Lateral curvature of the finger, most commonly affecting the fifth digit 4
• Often associated with a cone-shaped epiphysis or dysplasia on the radial margins of the epiphysis and diaphysis 4
• Frequently seen in Down syndrome and other genetic conditions 4

Polydactyly

• Presence of extra digits, can be preaxial (thumb side) or postaxial (little finger side) 5
• Postaxial polydactyly (duplicated fifth digit) is the most common form 5
• May occur in isolation or as part of genetic syndromes 5
• When associated with syndromes, trisomy 13, Meckel syndrome, and Down syndrome are common causes 5

Brachymesophalangia

• Shortening of the middle phalanx, often of the fifth finger 4
• Frequently associated with clinodactyly 4
• Common in Down syndrome 1

Clinical Implications and Management

• Fifth digit abnormalities may be isolated findings or important diagnostic clues to underlying genetic syndromes 2
• When identified, a thorough evaluation for associated anomalies should be conducted, particularly cardiac defects which are common in many of these syndromes 2
• Genetic testing should be considered when fifth digit abnormalities are found in conjunction with other dysmorphic features, developmental delay, or congenital anomalies 2
• Surgical correction may be indicated for functional or cosmetic reasons, particularly in cases of polydactyly 6

Diagnostic Approach

• Radiographic evaluation is essential to characterize the specific bone abnormality 4
• Chromosomal microarray analysis should be considered for patients with fifth digit abnormalities and additional features suggestive of a genetic syndrome 2
• Targeted genetic testing based on associated features (e.g., FISH for 22q11.2 deletion or 7q11.23 deletion) 2
• Consider whole exome sequencing when specific genetic syndromes are suspected but targeted testing is negative 2

Fifth digit abnormalities are important physical findings that can help identify underlying genetic conditions. Their presence should prompt careful evaluation for associated anomalies and appropriate genetic testing.