Chromosome affected: 7p13
Gene affected: GLI3 transcription factor
Inheritance: autosomal dominant with variable penetrance
Key clinical findings:
(1) hypothalamic hamartoblastoma on the floor of the third ventricle posterior to the optic chiasm
(2) pituitary aplasia, hypoplasia or dysplasia with panhypopituitarism
(3) mesoaxial (central) polydactyly: increased digits, with Y-shaped metacarpal bones in the hands and metatarsal bones in the foot
(4) postaxial polydactyly (PAP) on the ulnar aspect of the forearm or fibular aspect of the lower leg. This is termed PAP-A if a well-formed digit is present and PAP-P if a rudimentary digit is present.
(5) bifid epiglottis
Other findings:
(1) genitourinary malformations (cystic malformations, renal hypoplasia, ectopic ureteral implantation)
(2) imperforate anus, anal stenosis, rectal aplasia
(3) pulmonary segmentation anomalies
(4) short limbs
(5) facial malformations (flat nasal bridge, flat midface, short nose, anteverted nares, bathroacephaly, micrognathia)
(6) external ear malformations
(7) dysplastic tracheal cartilage
(8) nail dysplasia
(9) cleft palate or lip
(10) cleft uvula or larynx
plus a long list of other malformations
The diagnosis can be made if the patient:
(1) has a hypothalamic hamartoma and central polydactyly.
(2) has a first degree relative with PHS and a hypothalamic hamartoma
(3) has a first degree relative with PHS and central polydactyly.
(4) has a first degree relative with PHS and postaxial polydactyly type B and not of central African descent
A patient may have PHS (and should be tested for GLI3 mutations) if:
(1) postaxial polydactyly and hypothalamic hamartoma
(2) central polydactyly not meeting above criteria for diagnosis
(3) hypothalamic hamartoma without central or postaxial polydactyly
