RESUMEN
Infantile juvenile polyposis is a rare disease with severe gastrointestinal symptoms and a grave clinical course. Recently, 10q23 microdeletions involving the PTEN and BMPR1A genes were found in four patients with infantile juvenile polyposis. It was hypothesized that a combined and synergistic effect of the deletion of both genes would explain the condition. Subsequently, however, a patient with a larger 10q23 deletion including the same genes but with a mild clinical phenotype was identified. Here, we present four additional patients with 10q23 microdeletions involving the PTEN and BMPR1A genes. The sizes of the deletions were analyzed using single nucleotide polymorphism array analysis. All patients had macrocephaly, dysmorphic features, retardation and congenital abnormalities. One patient developed colorectal cancer. However, only one case had disease onset before 2 years of age and severe symptoms requiring colectomy. No clear correlation was found between ages at onset or severity of gastrointestinal symptoms and the sizes of the deletions. We conclude that patients with 10q23 microdeletions involving the PTEN and BMPR1A genes have variable clinical phenotypes, which cannot be explained merely by the deletion sizes. The phenotypes are not restricted to severe infantile juvenile polyposis but include childhood-onset cases with macrocephaly, retardation, mild gastrointestinal symptoms and possibly early-onset colorectal cancer.
Asunto(s)
Receptores de Proteínas Morfogenéticas Óseas de Tipo 1/genética , Cromosomas Humanos Par 10 , Enfermedades Gastrointestinales/genética , Poliposis Intestinal/genética , Fosfohidrolasa PTEN/genética , Eliminación de Secuencia , Anomalías Múltiples/genética , Edad de Inicio , Preescolar , Neoplasias Colorrectales/etiología , Femenino , Enfermedades Gastrointestinales/complicaciones , Enfermedades Gastrointestinales/patología , Humanos , Lactante , Recién Nacido , Discapacidad Intelectual/genética , Poliposis Intestinal/complicaciones , Poliposis Intestinal/patología , Masculino , Análisis de Secuencia por Matrices de Oligonucleótidos , FenotipoAsunto(s)
Deleción Cromosómica , Cromosomas Humanos Par 22/genética , Cromosomas Humanos Par 7/genética , Mucosa Bucal/ultraestructura , Síndrome de Williams/genética , Mejilla , Aberraciones Cromosómicas/diagnóstico , Aberraciones Cromosómicas/genética , Trastornos de los Cromosomas , Cósmidos/genética , Humanos , Hibridación Fluorescente in Situ/métodos , Mucosa Bucal/citología , Síndrome , Síndrome de Williams/diagnósticoRESUMEN
OBJECTIVE: The presentation of sonographic and perinatal findings of tetrasomy 9p. METHODS AND RESULTS: Chorionic villus sampling and amniocentesis were performed at 19 weeks of gestation because of the sonographic findings of Dandy-Walker malformation with bilateral ventriculomegaly. Cytogenetic analysis showed 47,XX,+i psu dic(9)(pter->q12::q12>-pter). The pregnancy was terminated at 20 weeks of gestation at the request of the parents. At post-mortem examination, the presumed hypoplasia of the vermis could not be confirmed for technical reasons. No other pathological findings were seen. CONCLUSION: From our experience and from the literature, we conclude that Dandy-Walker malformation is an important finding in tetrasomy 9p. Chromosomal studies should be carried out in fetuses with sonographically detected Dandy-Walker malformation, even in the absence of other abnormalities.