Pallister Hall syndrome:early diagnosis and natural history. N.J. Mendelsohn1,2, C. Ludowese1,2, R. Kriel1,2, O.A. Schirripa3, D.K. Manchester3, L.G. Biesecker4. 1) Dept Pediatrics/Med Genetics, Hennepin County Medical Center, Minneapolis, MN; 2) University of Minnesota, Minneapolis, MN; 3) University of Colorado Health Sciences Center; 4) GDRB, NIH/NHGRI, Bethesda, MD.
Pallister Hall Syndrome(PHS) is a condition with hypothalmic hamartoma(HH), polydactyly, bifid epiglottis and visceral anomalies. Hall et al first delineated the syndrome in 1980. Multiple case reports have broadened the diagnostic features from a lethal presentation to one where multiple generations are affected in an autosomal dominant manner. We report two infants diagnosed at an early age with a large HH and polysyndactyly. These infants demonstrate the imporance of early recognition and diagnosis as well as the natural history of PHS.
A 1st patient presented at ten weeks of age with polydactyly and feeding difficulties. ENT consultation revealed bifid epiglottis. A cerebral MRI disclosed a large suprasellar mass. Neurosurgical resection was planned but afer extensive discussion and evidence of no change in size of the mass, He was diagnosed with a benign HH as part of the PHS. A 2nd child presented at 16 days of age with polysyndactyly and a UTI. Further evaluation revealed an anterior rectal fistula. MRI of her head disclosed a HH. We present photographs of the children, subsequent MRIs, growth charts and results of endocrinologic evaluations.
These cases demonstrate important clinical aspects of Pallister Hall Syndrome. Polysyndactyly of PHS is typically central or postaxial and careful attention should be paid to families with four limb polydactyly. This in combination with midline defects should prompt a cerebral MRI. The correlation with these children's other congential malformations provided the correct diagnoses and avoided surgical removal of a major portion of their hypothalamic regions. Characteristically of PHS, the tumors have now been followed with no enlargement of the hamartoma and no evidence of malignant transformation. PHS has been mapped to 7p13. Biesecker et al reported two PHS families with frameshift mutations in GLI3. Evaluation of the GLI3 region is in progress for these children.