RESUMO
Holoprosencephaly (HPE) is failure of the forebrain to divide completely during embryogenesis. Incomplete penetrance has not been reported previously in SIX3 whole gene deletions, which are known to cause HPE. Both chromosomal microarray and whole exome sequencing (WES) were used to evaluate families with inherited HPE. Two families showed inherited deletions that contain SIX3 and were incompletely penetrant for HPE. Using WES, we ruled out parental mosaicism, a SIX3 hypomorph, and clinically significant variants in genes that are known to interact with SIX3 as causes of incomplete penetrance. We demonstrate the importance of molecular cascade testing in families with HPE and we answer important questions about incomplete penetrance.
Assuntos
Proteínas do Olho/genética , Deleção de Genes , Holoprosencefalia/genética , Proteínas de Homeodomínio/genética , Proteínas do Tecido Nervoso/genética , Prosencéfalo/anormalidades , Adulto , Pré-Escolar , Expressão Gênica , Holoprosencefalia/diagnóstico , Holoprosencefalia/metabolismo , Holoprosencefalia/patologia , Humanos , Lactente , Recém-Nascido , Análise em Microsséries , Proteínas do Tecido Nervoso/deficiência , Penetrância , Prosencéfalo/metabolismo , Sequenciamento do Exoma , Proteína Homeobox SIX3RESUMO
Turcot syndrome is a rare inherited condition of colonic polyposis associated with central nervous system tumors. We report a patient with a novel adenomatous polyposis coli gene mutation leading to a severe phenotype including medulloblastoma, low-grade fibromyxoid sarcoma following cranial radiation, pilomatrixomas, colonic adenomas, and abdominal desmoid tumor following colectomy, all of which were successfully treated. Multiple tumors may be seen in patients with Turcot syndrome but the occurrence of sarcomas is rare. This case highlights the importance of close follow-up for patients with Turcot syndrome and the importance of a broad differential diagnosis in evaluating a condition in which multiple tumors are frequently seen.
