Mosaic Trisomy 8

Mosaic trisomy 8 is a chromosomal disorder defined by the presence of three copies of chromosome 8 in some cells of the organism. It is characterized by facial dysmorphism, mild intellectual deficit and joint, urinary, cardiac and skeletal anomalies.

Epidemiology

Annual incidence varies between 1/25,000 and 1/50,000. Males are more frequently affected than females (sex-ratio 5:1).

Clinical description

Facial dysmorphic features are mild and include elongation of the skull (scaphocephaly), prominent forehead, hypertelorism, deeply set eyes (50%), broad upturned nose (60%), micrognathia (with everted lower lips), large dysplastic ears with prominent anthelices and large lobules. Additional features include: agenesis of the corpus callosum, highly arched or cleft palate (8%), short and large neck, high stature, elongated thin trunk, and narrow shoulder and pelvis. Urinary (hydronephrosis, ureteral reflux) and cardiac and large vessels abnormalities are frequent (40% and 25% respectively). Camptodactyly (70%), arthrogryposis of the joints (aggravating with time), deep palmar (in infants) and plantar furrows (75%), absent or hypoplastic patellae, vertebral malformations (65%: segmentation anomalies, costal anomalies, scoliosis...) as well as corneal opacity and strabismus are also commonly observed. Most patients present a moderate intellectual deficit (IQ between 50 and 75), with some patients having a normal intelligence. There is no correlation between the percentage of trisomic cells and the severity of the intellectual deficit.

Etiology

Mosaic trisomy 8 is the result of a post-zygotic event (error in chromosome segregation during mitosis in a fetus having a normal karyotype or spontaneous correction of trisomy 8). Complete trisomy 8 is due to an error in chromosome segregation during meiosis and often results in miscarriage during the first trimester. When, exceptionally, the fetus survives, it presents the same phenotype as mosaic trisomy. Patients with isochromosome 8p (tetrasomy of the short arm (p) of chromosome 8) have the same phenotype as patients with trisomy 8p (see this term).

Diagnostic methods

Diagnosis is based on karyotype analysis.

Antenatal diagnosis

Antenatal diagnosis is possible by cytogenetic studies. Corpus callum agenesis is the most important antenatal echographic criterion for the diagnosis of the syndrome.

Genetic counseling

Genetic counseling is reassuring, as trisomy 8 is almost always a de novo incident and presents a low risk of recurrence.

Management and treatment

Management requires a multidisciplinary approach. In some cases, cardiac surgery may be proposed.

Prognosis

Mosaic trisomy 8 seems to predispose to Wilms tumors, myelodysplasias and myeloid leukemia (see these terms). Some mosaic trisomy 8 patients have had children. In absence of serious malformations, life expectancy is normal.