The Principles of Clinical Cytogenetics - Extra Materials - Springer

Genomic Imprinting and Uniparental Disomy 529
been reported in three cases, hypospadias in two, and congenital cardiac anomalies were observed in
five cases, with an atrioventricular (A-V) canal defect in one and atrial septal defect (ASD) and
ventricular septal defect (VSD) in four. Subtle but apparently characteristic facial dysmorphisms
(slightly upslanted palpebral fissures, almond-shaped eyes, broad nasal root, upturned nares, long
philtrum, thin upper lip, prominent ears, and triangular face) might exist (235,237,239). In addition,
in a recent study, statistical analysis performed on a large series of mosaic trisomy 16 cases with
molecular determination of UPD status indicated that upd(16)mat was associated with fetal growth
restriction and with increased risk of major malformation (241). Although not yet certain, the existence
of an imprinting effect as a result of maternal UPD 16 is a distinct possibility.
upd(16)pat
A single case of paternal UPD for chromosome 16 has been reported (242). This case was associated
with confined placental mosaicism (see Chapter 12). Paternal isodisomy for chromosome 16
was prenatally diagnosed and confirmed after birth. IUGR was present with catch-up growth observed
at 13 months of age. Minor physical abnormalities included bilateral pes calcaneus and an
additional rudimentary mandibular dental arch. Psychomotor development was normal. It is not clear
whether paternal UPD 16 has an imprinting effect.
upd(17)mat
A single case of maternal UPD involving the entire chromosome 17 was reported in a 2-year-old boy
with trisomy 17 confined placental mosaicism (see Chapter 12) (243). His growth and psychomotor
development was normal. There is no evidence that maternal UPD 17 confers an imprinting effect.
upd(20)mat
Three cases of maternal UPD 20 have been reported (244–246). One of them was associated with
a mosaic cell line containing a small marker chromosome consisting of the pericentromeric region of
chromosome 20, and another was associated with confined placental mosaicism (see Chapter 12) for
trisomy 20. The common features in these three patients at ages 4 years, 35 months, and 17 months,
respectively, are prenatal and postnatal growth retardation. Isolated findings included mild facial
dysmorphism, strabismus, microcephaly, macrocephaly, developmental delay, and hyperactivity. It
is not clear whether maternal UPD 20 has an imprinting effect.
upd(20)pat
No pure paternal UPD involving the entire chromosome 20 has been reported. One case had a
structurally abnormal chromosome 20 derived from a terminal rearrangement that joined two chromosomes
20 at band p13 (247). DNA polymorphism studies indicated that the two chromosomes 20
in this terminal rearrangement were derived from one paternal chromosome, thereby representing
paternal isodisomy. The patient had multiple anomalies, including anotia, microcephaly, congenital
heart disease, and Hirschsprung disease. However, this case was complicated by the presence of
trisomy 20 cells in skin and the possibility of deletion of genes at the terminal rearrangement site.
Therefore, although an imprinting effect is possible for paternal UPD 20, a definitive conclusion
cannot be drawn without further case reports.
upd(21)mat
Maternal UPD for chromosome 21 has been reported in two patients (248,249). Both had a balanced
de novo (21;21) Robertsonian translocation (see Chapters 3 and 9) and were phenotypically
normal. Although maternal UPD 21 has been reported in early abortus specimens (250), it has not
been possible to clearly attribute embryonal death to UPD. Therefore, maternal UPD 21 might be
considered at this time to have no imprinting effect.