Pallister-Hall syndrome displays a wide range of severity and is characterized by hypothalamic hamartomas seen as a mass at the floor of the third ventricle, posterior to the optic chiasm 3,4.
Pallister-Hall syndrome is rare and the exact prevalence is unknown. Patients with postaxial polydactyly and asymptomatic hypothalamic hamartomas or bifid epiglottis may be misdiagnosed as having non-syndromic postaxial polydactyly type A 4.
- endocrine abnormalities ranging from asymptomatic to panhypopituitarism as a result of hypothalamic hamartoma 5
- limb malformations 4
- bifid epiglottis
- anal atresia
- renal anomalies, e.g horseshoe kidney, renal hypoplasia/agenesis, renal ectopia 4
- genitourinary anomalies, e.g hydrometrocolpos
- pulmonary segmentation anomalies, e.g bilateral bilobed lungs
- craniofacial abnormalities, e.g cleft palate, cleft uvula, cleft larynx, buccal frenula, low set and posteriorly angulated ears
There is a heterozygous genetic mutation in GLI3 located on chromosome 7p14.1 which is a zinc finger transcriptional activator protein 3,4. On histology, there are disordered arrangements of hyperplastic neurons admixed with astrocytes and minimal white matter which shows varying degrees of myelination 3.
Craniofacial abnormalities are thought to be a result of disruption of the midline development by the hypothalamic hamartoma 3.
MRI is the imaging modality of choice for hypothalamic hamartoma. They appear as non-calcified, non-enhancing and homogeneously isointense to grey matter on T1 weighted images and often hyperintense on T2 weighted images 3. These findings are helpful in distinguishing hypothalmic hamartoma from more common suprasellar lesions such as craniopharyngioma 3.
Treatment and prognosis
Prognosis in those with no known family history is based on the severity of the malformations present. The early lethality phenotype is likely associated with panhypopituitarism, severe airway malformation such as laryngotracheal clefts and / or unrecognised imperforate anus 4.
The following conditions contain overlapping clinical features 3:
- Ellis-van Crevald syndrome
- Smith-Lemil-Opitz syndrome
- oral-facial-digital syndrome type IV
- Kaufman-McKusick syndrome
- Greig cephalosyndactyly syndrome
- 1. Shaw-Smith C. Oesophageal atresia, tracheo-oesophageal fistula, and the VACTERL association: review of genetics and epidemiology. J. Med. Genet. 2005;43 (7): 545-54. doi:10.1136/jmg.2005.038158 - Free text at pubmed - Pubmed citation
- 2. Pallister-Hall Syndrome from Gene Reveiws, from NCBI. Pallister-Hall Syndrome
- 3. Kuo JS, Casey SO, Thompson L et-al. Pallister-Hall syndrome: clinical and MR features. AJNR Am J Neuroradiol. 20 (10): 1839-41. AJNR Am J Neuroradiol (full text) - Pubmed citation
- 4. Pallister-Hall Syndrome. (2017) Pubmed
- 5. Hall JG, Pallister PD, Clarren SK, Beckwith JB, Wiglesworth FW, Fraser FC, Cho S, Benke PJ, Reed SD. Congenital hypothalamic hamartoblastoma, hypopituitarism, imperforate anus and postaxial polydactyly--a new syndrome? Part I: clinical, causal, and pathogenetic considerations. (1980) American journal of medical genetics. 7 (1): 47-74. doi:10.1002/ajmg.1320070110 - Pubmed