Mosaic Trisomies 8, 9, and 16




Abstract


The most severe trisomies usually result in early pregnancy loss. However, some of these severe trisomies may survive to birth if they are mosaics, in which the condition only affects a portion of the cells in the body. Trisomy 8 mosaicism (Warkany syndrome 2) has a range of clinical phenotypes depending on the cell lines affected. Common findings include agenesis of the corpus callosum, hydrocephalus, ventriculomegaly, abnormal facies, cardiac malformations, and joint contractures. Children have progressive neurodevelopmental delay, although life expectancy may be normal. Trisomy 9 mosaicism is a rare disorder. Characteristic ultrasound findings include microcephaly, craniofacial defects, cardiac abnormalities, and limb findings. Most patients will die within the first year of life, and have severe intellectual and motor deficiencies. Trisomy 16 is the most common autosomal trisomy, although most will result in first-trimester pregnancy loss. All cases that survive to birth are mosaic trisomy 16. Ultrasound findings include cardiac anomalies, pulmonary hypoplasia, genitounrinary anomalies, growth restriction, and two-vessel umbilical cord. The outcome of mosaic trisomy 16 depends on the cell lines affected.




Keywords

mosaicism

 




Introduction


Trisomies can occur with any chromosome, but most often result in spontaneous abortion. For example, trisomy 16 is the most common trisomy in human pregnancies, and the majority of the time results in miscarriage. These severe trisomies are more likely to survive past the first trimester and possibly to birth if they are mosaics, in which the condition of trisomy only affects a portion of the cells in the body. Here, we discuss mosaic trisomies 8, 9, and 16.




Disorder


Trisomy 8


Definition


Trisomy 8 mosaicism is a genetic abnormality that results from a cell line with an extra chromosome number 8 in addition to a genetically normal cell line. Trisomy 8 mosaicism is also called Warkany syndrome 2. Unlike some other trisomies, trisomy 8 mosaicism can be compatible with life. These individuals vary in phenotype and can be recognized by mental retardation, abnormal facies, absent or dysplastic patellas, joint contractures, plantar/palmar furrows, distinctively abnormal toe posture, vertebral anomalies, narrow pelvis, and urorenal anomalies. 2


Prevalence and Epidemiology


Mosaic trisomy 8 is estimated in 2–4 : 100,000 births. Eight of 10 spontaneous abortions is due to complete trisomy 8, which is lethal in a conceptus. There is a 3 : 1 male-to-female sex ratio in the mosaic cases. 3 A review of PubMed’s database shows that only 120 cases have been reported.


Etiology and Pathophysiology


According to Fineman et al., chromosome 8 is the “largest autosome thus far found to be trisomic among live-born infants.” Most cases of trisomy 8 mosaicism result from mitotic nondisjunction.


Manifestations of Disease


Clinical Presentation


Mosaic trisomy 8 has a wide range of clinical phenotypes depending on the cell lines present. Individuals can be normal or have severe malformations. Twenty-five per cent of patients may have congenital cardiac malformations. Other physical findings of live-born infants with trisomy 8 mosaicism include mild-to-moderate mental retardation due to corpus callosum agenesis, strabismus, osseous and soft tissue abnormalities, broad bulbous nose, palate deformity, hydronephrosis, cryptorchidism, reduced joint mobility, various vertebral and costal anomalies, eye anomalies, camptodactyly, and deep plantar and palmar creases. Deep plantar creases are very characteristic of this disease.


Imaging Technique and Findings


Ultrasound.


Ultrasound (US) can identify cases of suspected trisomy 8 mosaicism. US findings include agenesis of the corpus callosum, hydrocephalus, abnormal facies, cardiac malformations, ventriculomegaly, and joint contractures.


Magnetic Resonance Imaging.


There are few cases that address magnetic resonance imaging (MRI) in trisomy 8 mosaicism. However, MRI can further characterize brain abnormalities, including enlarged lateral ventricles and corpus callosum agenesis, which exist in trisomy 8 mosaicism. One case report describes a 33-year-old man treated for Marfan syndrome during childhood who presented with “lumbar spine herniated nucleus propulsus” on MRI.




Differential Diagnosis From Imaging Findings




  • 1.

    Other trisomies


  • 2.

    Syndromes with Arthrogryposis

Other trisomies should be on the differential diagnosis for trisomy 8 mosaicism. Syndromes with arthrogryposis should be differentiated from trisomy 8 mosaicism. Both diagnoses include joint contractures. Arthrogryposis syndromes are multifactorial and it is often hard to find a cause.




Synopsis of Treatment Options


Prenatal


Most patients with mosaic trisomy 8 will be detected with chorionic villus sampling; however, the results are not specific. This is due to the fact that trisomy 8 mosaic found in the sample may be due to confined placental mosaicism. Like other chromosomal abnormalities, maternal serum alpha-fetoprotein (MSAFP) may be in trisomy 8 mosaicism. Amniocentesis can confirm the diagnosis.


Postnatal


Postnatal diagnosis of trisomy 8 mosaicism may be delayed because of the wide spectrum of phenotypes that exist. 2 Some individuals with trisomy 8 mosaicism may not be diagnosed until after birth when a child presents with progressive neurodevelopmental delay and dysmorphic facial features. Life expectancy may be normal. These children can be diagnosed with karyotyping on serum blood cells. Mosaic trisomy 8 individuals may have an increased risk of leukemia and myelodysplastic syndrome. This is a result of progenitor cell proliferation due to abnormal stromal cells.




Disorder


Trisomy 9


Definition


Trisomy 9 mosaicism is a genetic abnormality that results from a cell line that has an extra chromosome number 9 in addition to a genetically normal cell line.


Prevalence and Epidemiology


The earliest report of trisomy 9 mosaicism was in 1973. Trisomy 9 is extremely rare in live births. Only 0.1% of trisomy 9 conceptions will result in live birth with poor prognosis, with survival times ranging from mere minutes to 9 months after birth. Live-born fetuses will have a mosaic phenotype. Trisomy 9 affects both genders equally.


Etiology and Pathophysiology


Trisomy 9 mosaicism is a result of meiotic error with trisomy rescue. Similar to trisomy 16, trisomy 9 mosaicism increases with maternal age because the genetic error occurs in meiosis.


Manifestations of Disease


Clinical Presentation


Mosaic trisomy 9 has a similar phenotype to those individuals with pure trisomy 9. Individuals with the disease will most likely die within 1 year of age. Typical characteristics of this disease are “failure to thrive, severe intellectual and motor deficiency, cryptorchidism in males, and renal cysts.” Other physical findings of live-born infants with trisomy 9 mosaicism include bulbous nose and dislocated limbs.


Imaging Technique and Findings


Ultrasound.


US can identify cases of suspected trisomy 9 mosaicism. Characteristic findings have been noted in up to 60% of these individuals, including microcephaly, deep-set eyes, fleshy nose, receding lower lip, subluxation of hips, and cardiac disease. US findings are nonspecific for trisomy 9 mosaicism. The most common findings are intrauterine growth restriction and amniotic fluid disorders, followed by craniofacial, cardiac, skeletal, and urinary findings. In a review of 13 mosaic trisomy 9 fetuses, 7.7% had one single umbilical artery and 15.4% had gastrointestinal findings on US.


Magnetic Resonance Imaging.


There are few cases that address magnetic resonance imaging (MRI) in trisomy 9 mosaicism. Of note, most trisomy 9 mosaic individuals do not have CNS structural anomalies, and so MRI is unlikely to be of great clinical value.




Differential Diagnosis From Imaging Findings


Trisomy 18 in particular has similar sonographic findings as trisomy 9 mosaicism, as both contain facial and cardiac abnormalities. Trisomy 18 is the second most common autosomal trisomy occurring in 1 in 5500 live births. Similar to other chromosomal abnormalities, the disease can involve any organ. The phenotypic characteristics of trisomy 18 are intrauterine growth restriction, hypertonia, prominent occiput, small mouth, micrognathia, pointy ears, short sternum, horseshoe kidney, and flexed fingers, with the index finger overlapping the third finger and the fifth finger overlapping the fourth.

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Jul 7, 2019 | Posted by in OBSTETRICS & GYNAECOLOGY IMAGING | Comments Off on Mosaic Trisomies 8, 9, and 16
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