Polydactyly

Supernumerary digits on hands or feet. Three anatomic categories that map to different differentials:

• Postaxial (ulnar/fibular side, "pinky" side): the extra digit is on the small-finger side. The most common form; benign type B (skin tag without bone) is especially common in African ancestry.
• Preaxial (radial/tibial side, "thumb" side): the extra digit or duplication is on the thumb/great-toe side. More often syndromic.
• Central / mesoaxial: the extra digit is between the middle fingers; rarer and more often syndromic.

Postaxial polydactyly subdivides further: type A (fully formed extra digit with bone and joint) vs type B (rudimentary nubbin or skin tag without bone, often pedunculated). Type B in isolation, without other anomalies, is benign and managed with simple surgical removal.

Two questions decide the work-up:

1. Where is it (preaxial vs postaxial vs central)?
2. Is it isolated or syndromic? A careful exam for dysmorphism, growth, cardiac findings, midline defects, polydactyly in other relatives, and family history.

Postaxial type B in an otherwise normal infant of African ancestry with no other findings is benign and inherited as autosomal dominant (often GLI3); cosmetic removal is the only intervention. Any other combination (preaxial, central, type A, syndromic features, family history of syndromic disease) warrants a syndrome work-up. Polydactyly is a sentinel finding for several ciliopathies and pathway disorders that have systemic implications: renal cysts, retinitis pigmentosa, hypogonadism, learning differences (BBS); cleft and cardiac (trisomy 13); hypothalamic hamartoma (Pallister-Hall).

Isolated polydactyly

• Postaxial polydactyly type B, isolated (GLI3, AD; population: ~1:300 in African ancestry, ~1:3000 European): a skin tag without bone, removed for cosmesis. Family history of "extra finger" in unaffected adults is common.
• Preaxial polydactyly, isolated (often GLI3 AD; or SHH regulatory mutations including the ZRS): thumb duplication. Usually warrants imaging if bilateral or complex; Wassel classification grades the level of duplication.

Ciliopathies (typically postaxial)

The clinically critical group; postaxial polydactyly is a common phenotypic flag.

• Bardet-Biedl syndrome (BBS) (multiple BBS genes): postaxial polydactyly + retinitis pigmentosa + truncal obesity + hypogonadism + learning differences + renal anomalies. The most common cilipathy presenting with polydactyly. Confirm with multigene BBS panel.
• Meckel-Gruber syndrome (MKS1, MKS3, others): postaxial polydactyly + cystic kidneys + occipital encephalocele. Lethal in the neonatal period; the prenatal-loss differential.
• Joubert syndrome (AHI1, CEP290, others): polydactyly in a subset, with the molar tooth sign on brain MRI + hypotonia + ataxia + episodic hyperpnea + retinal/renal involvement.
• McKusick-Kaufman syndrome (MKKS; phenotypic overlap with BBS): postaxial polydactyly + hydrometrocolpos + congenital heart defect.
• Orofaciodigital syndrome type 1 (OFD1): X-linked, lethal in males; lobulated tongue + cleft palate + frontal bossing + polydactyly + polycystic kidneys.

GLI3-spectrum disorders

GLI3 encodes a transcription factor downstream of Sonic Hedgehog; allele-specific defects cause overlapping limb-and-CNS pictures.

• Greig cephalopolysyndactyly syndrome (GLI3, AD): preaxial polydactyly + macrocephaly + frontal bossing + hypertelorism + cutaneous syndactyly.
• Pallister-Hall syndrome (GLI3, AD): postaxial polydactyly + hypothalamic hamartoma (gelastic seizures, central precocious puberty) + imperforate anus + bifid epiglottis. The hypothalamic hamartoma is the defining feature.

Aneuploidy and microdeletions

• Trisomy 13 (Patau): postaxial polydactyly + holoprosencephaly + cleft lip/palate + congenital heart disease + scalp cutis aplasia + microphthalmia. The polydactyly is a flag in a polymalformed newborn.

Syndromes with polydactyly and other distinctive features

• Smith-Lemli-Opitz syndrome (DHCR7): 2-3 toe syndactyly is more classic, but polydactyly is described. Microcephaly + ptosis + anteverted nares + cleft palate + hypospadias + low cholesterol.
• Carpenter syndrome (RAB23, AR): preaxial polydactyly + craniosynostosis + obesity + cardiac defects + intellectual disability. (No condition leaf to link.)
• Ellis-van Creveld syndrome (EVC, EVC2, AR): postaxial polydactyly + short ribs + cardiac (single atrium common) + ectodermal dysplasia (small nails, natal teeth). Old-order Amish population.
• Cartilage-hair hypoplasia / McKusick metaphyseal dysplasia (RMRP, AR; Amish): not classically polydactylous, but short-limbed short stature + sparse hair + immune deficiency in the same patient population deserves mention to keep the Amish skeletal differential straight. (No condition leaf to link.)
• Short-rib polydactyly syndromes (Saldino-Noonan, Majewski): short ribs + polydactyly + visceral anomalies; lethal forms in the perinatal period.

The work-up is driven by which side and what else is present.

1. Careful exam: count digits, palpate for bone, note bilateral vs unilateral, note nail bed, document any skin tag (type B). Examine for syndromic features (face, growth, cardiac, abdominal mass for renal cysts, fundus for RP, palpebral fissures).
2. Radiographs of hands and feet: distinguish type A (bone present) from type B; classify Wassel level for preaxial thumb duplication.
3. Family history: three-generation pedigree, ask specifically about "extra finger" in adults (often surgically removed in childhood and forgotten).
4. Echocardiogram if any cardiac murmur, syndrome with cardiac association suspected, or trisomy 13 features.
5. Renal ultrasound if cilipathy suspected (BBS, Meckel-Gruber, Joubert, OFD1) or in any syndromic polydactyly.
6. Brain MRI if Joubert (molar tooth sign), Pallister-Hall (hypothalamic hamartoma), holoprosencephaly suspected.
7. Ophthalmologic exam with dilated funduscopy if BBS or other ciliopathy suspected (retinitis pigmentosa often emerges in late childhood).
8. Chromosomal microarray as first-tier for syndromic polydactyly with multiple anomalies.
9. Targeted gene panel: BBS panel (multiple genes), ciliopathy panel, GLI3 if Greig/Pallister-Hall features, DHCR7 + cholesterol panel if SLO suspected.
10. Exome / genome sequencing if pattern is unclear or initial panel negative.
11. Surgical removal of polydactylous digits is done for function and cosmesis; timing depends on the form (type B can be ligated in the nursery; type A requires formal surgery later).