Table 3. [GLI3 Allelic Disorders]. - GeneReviews®

Disorder	Clinical Features	Comment
Pallister-Hall syndrome (PHS)	Wide range of severity Central or postaxial polydactyly, hypothalamic hamartoma, bifid epiglottis, imperforate anus or anal stenosis, & other anomalies In a minority of individuals: multiple severe anomalies (e.g., pituitary dysplasia w/pan hypopituitarism & laryngeal clefts or other airway anomalies, which may be life threatening in the neonatal period)	It is often wrongly assumed that PHS is severe & GCPS is mild; most individuals w/PHS are mildly affected, w/polydactyly, asymptomatic bifid epiglottis, & hypothalamic hamartoma
Postaxial polydactyly type A (PAP-A) (OMIM 174200)	Limb malformation limited to presence of a single, well-formed supernumerary postaxial digit on 1 or both hands & feet	There is some controversy as to whether PAP-A is distinct from PHS or is instead a variant of PHS w/mild, subtle, & asymptomatic bifid epiglottis, hypothalamic hamartoma, anal stenosis, & other signs.
Preaxial polydactyly type IV (PPD-IV) (OMIM 174700)	Preaxial polydactyly of hands &/or feet w/o other malformations (typically the same pattern of syndactyly in hands & feet as those w/GCPS) Severity is highly variable. ¹	PPD-IV is essentially GCPS w/o craniofacial manifestations. Because macrocephaly occurs in the general population & is common in GCPS, the presence of macrocephaly in a person w/apparently isolated PPD-IV may be difficult to interpret.
Acrocallosal syndrome	Postaxial polydactyly, macrocephaly, agenesis of the corpus callosum, & severe developmental delay	2 individuals diagnosed w/acrocallosal syndrome have been reported w/missense variants in GLI3. ²

Disorder

Clinical Features

Comment

Wide range of severity
Central or postaxial polydactyly, hypothalamic hamartoma, bifid epiglottis, imperforate anus or anal stenosis, & other anomalies
In a minority of individuals: multiple severe anomalies (e.g., pituitary dysplasia w/pan hypopituitarism & laryngeal clefts or other airway anomalies, which may be life threatening in the neonatal period)

It is often wrongly assumed that PHS is severe & GCPS is mild; most individuals w/PHS are mildly affected, w/polydactyly, asymptomatic bifid epiglottis, & hypothalamic hamartoma

Postaxial polydactyly type A (PAP-A)
(OMIM 174200)

Limb malformation limited to presence of a single, well-formed supernumerary postaxial digit on 1 or both hands & feet

There is some controversy as to whether PAP-A is distinct from PHS or is instead a variant of PHS w/mild, subtle, & asymptomatic bifid epiglottis, hypothalamic hamartoma, anal stenosis, & other signs.

Preaxial polydactyly type IV (PPD-IV)
(OMIM 174700)

Preaxial polydactyly of hands &/or feet w/o other malformations (typically the same pattern of syndactyly in hands & feet as those w/GCPS)
Severity is highly variable. ¹

PPD-IV is essentially GCPS w/o craniofacial manifestations.
Because macrocephaly occurs in the general population & is common in GCPS, the presence of macrocephaly in a person w/apparently isolated PPD-IV may be difficult to interpret.

Acrocallosal syndrome

Postaxial polydactyly, macrocephaly, agenesis of the corpus callosum, & severe developmental delay

2 individuals diagnosed w/acrocallosal syndrome have been reported w/missense variants in GLI3. ²

From: Greig Cephalopolysyndactyly Syndrome

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Adam MP, Feldman J, Mirzaa GM, et al., editors.

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