Prenatal diagnosis of chromosome 4 mosaicism: prognostic role of cytogenetic, molecular, and ultrasound/MRI characterization.
Trisomy 4 mosaicism is extremely rare: herein we report the cytogenetic and molecular characterization and prenatal US findings of a case diagnosed prenatally. The diagnosis of level III mosaicism was established in cultured amniotic fluid cells (22.5%). At 22 weeks gestation, micrognathia and hypotelorism were suspected at 2-D sonography, and confirmed at 3-D examination. In addition, 2-D US showed cerebellar hypoplasia associated with borderline ventriculomegaly (confirmed at magnetic resonance imaging, MRI), spine deformity (hemivertebra), and a complete atrioventricular septal defect (AVSD). The pregnancy was terminated. Trisomy 4 mosaicism was confirmed in placental and fetal skin cultured cells. The cord blood karyotype was normal. Molecular analysis excluded uniparental disomy of chromosome 4, and indicated that the trisomy 4 was of maternal meiotic origin. In presence of chromosome 4 mosaicism, accurate fetal sonography and echocardiography are mandatory. Low level mosaicism and normal echographic examinations seem to be associated with good prognosis. In postnatal life, chromosome 4 mosaicism should be suspected, and cytogenetic analysis proposed of further tissues (i.e., skin), in presence of craniofacial dysmorphism, cardiac defects, and abnormal hands/feet, even if mental development is appropriate or only slightly impaired.
Gentile
Mattia
M
Department of Medical Genetics, I.R.C.C.S. Saverio de Bellis, Castellana Grotte, Bari, Italy. mattiagentile@libero.it
Volpe
Paolo
P
Cariola
Filomena
F
Di Carlo
Antonio
A
Marotta
Vincenzo
V
Buonadonna
Antonia Lucia
AL
Boscia
Filippo Maria
FM
D000015:Abnormalities, Multiple / Q000175:diagnosis / Q000196:embryology / Q000235:genetics; D000328:Adult; D002894:Chromosomes, Human, Pair 4 / Q000235:genetics*; D017809:Fatal Outcome; D005260:Female; D005313:Fetal Death; D005315:Fetal Diseases / Q000175:diagnosis / Q000235:genetics; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D007223:Infant; D007621:Karyotyping; D008279:Magnetic Resonance Imaging; D009030:Mosaicism; D011247:Pregnancy; D011379:Prognosis; D014314:Trisomy; D016216:Ultrasonography, Prenatal