RESUMO
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 Invasive care was ultimately withdrawn, and the patient expired at three months of age.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.
Assuntos
Anus Imperfurado/diagnóstico , Anus Imperfurado/genética , Doença de Hirschsprung/diagnóstico , Doença de Hirschsprung/genética , Síndrome de Pallister-Hall/diagnóstico , Síndrome de Pallister-Hall/genética , Anus Imperfurado/cirurgia , Biópsia , Hibridização Genômica Comparativa , Evolução Fatal , Feminino , Doença de Hirschsprung/cirurgia , Humanos , Recém-Nascido , Cariótipo , Fatores de Transcrição Kruppel-Like/genética , Mutação , Proteínas do Tecido Nervoso/genética , Fenótipo , Gravidez , Índice de Gravidade de Doença , Tomografia Computadorizada por Raios X , Ultrassonografia Pré-Natal , Proteína Gli3 com Dedos de ZincoRESUMO
9q22.3 microdeletion syndrome is a well-described contiguous deletion syndrome with features of Gorlin syndrome and other manifestations. Commonly reported findings in addition to those of Gorlin syndrome include metopic craniosynostosis, hydrocephalus, intellectual disability, and minor facial anomalies. The critical region for this condition was found to include the PTCH1 and FANCC genes; however, other genes are often deleted in affected individuals but their role in the observed phenotype is not understood. Fewer than 50 individuals with 9q22.3 microdeletion have been reported, all diagnosed postnatally on the basis of the phenotype. A confirmed prenatal diagnosis and accompanying fetal imaging has not been reported to date. We describe a patient with prenatally diagnosed 9q22.3 microdeletion syndrome following the ultrasonographic identification of trigonocephaly, macrosomia, organomegaly, ventriculomegaly, and anomalous vertebrae.