title: Total colonic aganglionosis and imperforate anus in a severely affected infant with Pallister-Hall syndrome.
abstract: Pallister-Hall syndrome is a complex malformation syndrome characterized by a wide range of anomalies including hypothalamic hamartoma, polydactyly, bifid epiglottis, and genitourinary abnormalities. It is usually caused by truncating frameshift/nonsense and splicing mutations in the middle third of GLI3. The clinical course ranges from mild to lethal in the neonatal period. We present the first patient with Pallister-Hall syndrome reported with total colonic aganglionosis, a rare form of Hirschsprung disease with poor long-term outcome. The patient also had an imperforate anus, which is the third individual with Pallister-Hall syndrome reported with both Hirschsprung disease and an imperforate anus. Molecular testing via amniocentesis showed an apparently de novo novel nonsense mutation c.2641 C>T (p.Gln881*). His overall medical course was difficult and was complicated by respiratory failure and pan-hypopituitarism. Invasive care was ultimately withdrawn, and the patient expired at three months of age. This patient's phenotype was complex with unusual gastrointestinal features ultimately leading to a unfavorable prognosis and outcome, highlighting the range of clinical severity in patients with Pallister-Hall syndrome.
authors.affiliation: Division of Human Genetics, Department of Pediatrics, University of Pennsylvania Perelman School of Medicine and The Children's Hospital of Philadelphia, Philadelphia, Pennsylvania.
authors.forename: Mindy H
authors.initials: MH
authors.lastname: Li
authors.forename: Moriah
authors.initials: M
authors.lastname: Eberhard
authors.forename: Pamela
authors.initials: P
authors.lastname: Mudd
authors.forename: Luv
authors.initials: L
authors.lastname: Javia
authors.forename: Robert
authors.initials: R
authors.lastname: Zimmerman
authors.forename: Nahla
authors.initials: N
authors.lastname: Khalek
authors.forename: Elaine H
authors.initials: EH
authors.lastname: Zackai
mesh_terms: D001006:Anus, Imperforate / Q000175:diagnosis* / Q000235:genetics* / Q000601:surgery; D001706:Biopsy; D055028:Comparative Genomic Hybridization; D017809:Fatal Outcome; D005260:Female; D006627:Hirschsprung Disease / Q000175:diagnosis* / Q000235:genetics* / Q000601:surgery; D006801:Humans; D007231:Infant, Newborn; D059785:Karyotype; D051741:Kruppel-Like Transcription Factors / Q000235:genetics; D009154:Mutation; D009419:Nerve Tissue Proteins / Q000235:genetics; D054975:Pallister-Hall Syndrome / Q000175:diagnosis* / Q000235:genetics*; D010641:Phenotype; D011247:Pregnancy; D012720:Severity of Illness Index; D014057:Tomography, X-Ray Computed; D016216:Ultrasonography, Prenatal; D000074290:Zinc Finger Protein Gli3
chemical_list: C065683:GLI3 protein, human; D051741:Kruppel-Like Transcription Factors; D009419:Nerve Tissue Proteins; D000074290:Zinc Finger Protein Gli3
keywords: GLI3; Hirschprung disease; Pallister-Hall Syndrome; imperforate anus; total colonic aganglionosis