RESUMEN
OBJECTIVE: The purpose of this study was to elucidate the facial morphology and the pattern of internal malformations in three fetuses with RS born to first cousins of Egyptian decent. METHODS: The fetal ultrasonography findings were highly suggestive of RS leading to targeted Sanger sequencing of FAM20C and postnatal assessment. RESULTS: The prenatal ultrasound findings of osteosclerotic skull, exorbitism, hypoplastic nose, midface hypoplasia, small mouth with down-curved corners, and a distinct and recognizable pattern of intracranial calcification were identified in three fetuses with RS. The calcifications were evident specifically around the corpus callosum and/or ventricular walls. Ectopic renal and hepatic calcifications, pulmonary hypoplasia, mild rhizomelic shortening of the upper limbs, intrauterine fractures, and cerebellar hypoplasia were also noted. Molecular analysis identified three novel homozygous variants, two frameshift: [c.456delC (p.Gly153Alafs*34)] in exon 1 and [c.905delT (Phe302Serfs*35)] in exon 4 and one nonsense mutation in exon 10, [c.1557C>G(p.Tyrs519*)]. The three variants were segregated with the phenotype. This is the first description of a phenotype associated with homozygous truncating variants of FAM20C. CONCLUSION: RS has characteristic prenatal ultrasound findings which can improve the prenatal identification of this condition and help in guiding the molecular diagnosis and counseling.
Asunto(s)
Anomalías Múltiples/diagnóstico por imagen , Fisura del Paladar/diagnóstico por imagen , Exoftalmia/diagnóstico por imagen , Microcefalia/diagnóstico por imagen , Osteosclerosis/diagnóstico por imagen , Adulto , Facies , Femenino , Humanos , Fenotipo , Embarazo , Ultrasonografía PrenatalRESUMEN
OBJECTIVE: Deterioration in ventricular function is often observed in patients treated with anthracyclines for cancer. There is a paucity of evidence on interventions that might provide cardio-protection. We investigated whether prophylactic use of carvedilol can prevent doxorubicin-induced cardiotoxicity and whether any observed effect is dose related. METHODS: A prospective, randomized, double-blind study in patients treated with doxorubicin, comparing placebo (nâ¯=â¯38) with different doses of carvedilol [6.25â¯mg/day (nâ¯=â¯41), 12.5â¯mg/day (nâ¯=â¯38) or 25â¯mg/day (nâ¯=â¯37)]. The primary endpoint was the measured change in left ventricular ejection fraction (LVEF) from baseline to 6 months. RESULTS: LVEF decreased from 62⯱â¯5% at baseline to 58⯱â¯7% at 6-months (pâ¯=â¯0.002) in patients assigned to placebo but no statistically significant changes were observed in any of the 3 carvedilol groups. At 6 months, only one of 116 patients (1%) assigned to carvedilol had an LVEFâ¯<â¯50% compared to four of the 38 assigned to placebo (11%), (pâ¯=â¯0.013). No significant differences were noted between carvedilol and placebo in terms of the development of diastolic dysfunction, clinically overt heart failure or death. CONCLUSIONS: Carvedilol might prevent deterioration in LVEF in cancer patients treated with doxorubicin. This effect may not be dose related within the studied range.