American Journal of Medical Genetics 137A:308–312 (2005)
Trisomy 20q13!20qter in a Girl With Multiple Congenital
Malformations and a Recombinant Chromosome 20
Inherited From a Paternal Inversion (20)(p13q13.1):
Clinical Report and Review of the Trisomy 20q Phenotype
Dorothy K. Grange,1* Jaime Garcia-Heras,1Ramzi A. Kilani,2and Stephen Lamp1
1Department of Pediatrics, Division of Medical Genetics, Washington University School of Medicine, St. Louis, Missouri
2Department of Pediatrics, Division of Newborn Medicine, Washington University School of Medicine, St. Louis, Missouri
We report on a patient with a rec(20)dup(20q)
chromosome 20 inversion [inv(20)(p13q13.1)]. The
rearrangement results in a duplication of 20q13.1
to 20qter and a deletion of 20p13 to 20pter. The
patient is a girl with craniofacial features and
multiple congenital malformations that overlap
with the abnormalities previously described in
trisomy 20q syndrome. To our knowledge this is
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chromosome 20 pericentric inver-
rearrangements. The few previously described cases were
rec(20)dup (20p) arising via recombination-aneusomy from
1986]. We present the first report of a rec(20)dup (20q) in a
newborn girl with multiple malformations that overlap with
trisomy 20q syndrome, describe her clinical course over 15
months after birth, and review the clinical features of trisomy
The patient was born at 40-weeks gestation by cesarean-
section to a 27-year-old G1P1 mother. The pregnancy was
uncomplicated. Apgar scores were 6 at 1 min and 7 at 5 min.
Family history was remarkable for ‘‘empty sella syndrome’’ in
the father with poor growth in childhood, and six lumbar
vertebrae in the paternal grandmother. There is no one else
with known birth defects or recurrent miscarriages.
The birth weight was 3,507 g (75th centile), the length was
51.5 cm (75–90th centile), and the OFC was 33 cm (10th
centile). Physical examination showed craniofacial dys-
morphic features. She had relative microcephaly, a low frontal
hairline with hirsutism of the forehead, thick scalp hair, deep
set eyes with short and upslanting palpebral fissures, blocked
tearducts, anupturned nosewithflaired nostrils, aprominent
a left preauricular pit, micro-retrognathia with protruding
upper lip, and creases in the skin of the chin (Fig. 1). Exam-
ination of the limbs showed bilateral fifth finger clinodactyly
with broad thumbs and mildly broad great toes. An echocar-
diogram demonstrated complex cardiac malformations con-
sisting of an atrioventricular canal, D-transposition of the
great vessels, hypoplastic right ventricle, pulmonary valve
atresia, hypoplastic pulmonary arteries, right aortic arch, and
aberrant right subclavian artery. Multiple thoracic hemiver-
tebrae (T7, T10, T11, T12), fusion of the right T7 hemivertebra
on radiographs. She had malrotation of the intestine that was
repaired in early infancy. There was a possible duplicated left
renal collecting system by ultrasound. A head ultrasound
study was normal, but no other brain imaging has been done.
The patient had poor feeding, requiring nasogastric tube
feedings and eventual placement of a gastrostomy tube at
5 months of age. Weight has been maintained at the 25th
now less than the 3rd centile and about 2.5–3 SD below the
mean. She has had two cardiac surgeries, a Blalock–Taussig
shunt procedure at 1 week of age, followed by repair of the
age. She has had developmental delays since birth. At the age
of 4½ months she was smiling and reaching for objects. Her
head control was poor and she was unable to roll over. By
9 months she was still not rolling over or sitting up. She was
normal. She has mild hyperopia. She had left nasolacrimal
At 15 months of age, she is said to be functioning at the 7–
8 month level developmentally. She is able to roll over and sits
without support, but she cannot get into a sitting position on
her own. She is beginning to bear weight on her feet and can
from hand to hand, but has a poor pincer grasp. She babbles
and makes a few vowel sounds, but says no words. She re-
ceives all of her feedings through the gastrostomy tube and
takes nothing by mouth. She has been healthy and no longer
requires medication for her cardiac problems.
A chromosome study on peripheral lymphocytes from the
patient by GTW banding identified an abnormal chromosome
20 with a deletion of 20p13 to 20pter and a duplicated 20q13.1
*Correspondence to: Dr. Dorothy K. Grange, M.D., Department
of Pediatrics, Division of Medical Genetics, Washington Univer-
sity School of Medicine, Campus Box 8116, 660 S. Euclid Ave.,
St. Louis, MO 63110. E-mail: firstname.lastname@example.org
Received 24 September 2004; Accepted 30 May 2005
? 2005 Wiley-Liss, Inc.
had a normal karyotype. The chromosome analysis in the
father revealed a pericentric inversion of chromosome 20. His
karyotype is 46,XY,inv(20)(p13q13.1) (Fig. 2b and Fig. 3). The
abnormal chromosome 20 in the patient was interpreted as
a meiotic recombinant inherited from the father via recom-
bination-aneusomy. FISH with subtelomeric probes for chro-
mosome 20 showed a normal chromosome 20 and the
recombinant with two subtelomeric 20q signals and no sub-
telomeric 20p signal (Fig. 4). The karyotype nomenclature is
46,XX,rec(20)dup (20q) inv(20)(p13q13.1)pat. It has not been
possible to study paternal relatives to determine if there are
other carriers of the same inversion.
Our patient represents the first description of a rec(20)dup
(20q) chromosome defect, which was inherited via recom-
bination-aneusomy from a paternal pericentric inversion of
chromosome 20. The resulting chromosomal imbalance is a
combination of trisomy of 20q13.1 to 20qter and a deletion of
The patient at different ages, (a) newborn, (b) 4 months, and (c) 9 months. [Color figure can be viewed in the online issue, which is available at
A number of patients with partial trisomy 20q have been
described. The rearrangements have typically been derived
from parental translocations through an abnormal meiotic
segregation [Plotner et al., 2002]. Thus, the 20q trisomy is
usually associated with a partial deletion of another chromo-
some, or anadditional partial duplication in a few cases, and it
has been difficult to determine a specific phenotype. However,
four previously reported patients with trisomy 20q13.1 to
20qter associated with relatively small or minor chromosome
deletions tentatively delineate a recognizable syndrome, with
craniofacial malformations, musculoskeletal abnormalities,
andcardiacdefects[Saxetal.,1986; Herensetal., 1990;Addor
epicanthal folds, deep-set small eyes, upslanting palpebral
ing chinwithskincreases,andcardiacmalformations. Abund-
other cases. Our patient had malrotation of the intestine,
died in early infancy, one at a few days of age due to complex
cardiac defects, including a truncus arteriosus, single ven-
tricle, and mitral valve atresia [Sax et al., 1986] and the other
at 5 months of age of an unknown cause [Herens et al., 1990].
Several patients with larger, essentially ‘‘pure’’ duplications
of 20q, from 20q11 to 20qter, have been described [Pierquin
et al., 1988; Waters et al., 1990]. Interestingly, the case
reported by Pierquin et al.  had almost the same cardiac
defects seen in our patient, including complete atrioventicular
canal, transposition of the great vessels, and pulmonary
with developmental delays.
It is difficult to assess the phenotypic impact of the deletion
from 20p13 to 20pter in our case because, to our knowledge,
there are no reports of similar deletions. A few cases of
del(20)(p12.2) reported previously are not comparable because
the deletions are larger. One of these patients was a 16-year-
old male with delayed psychomotor development, severe
behavioral problems, craniofacial dysmorphism, kyphoscolio-
sis, pectus carinatum, anomalies of the fingers and thumbs,
milder and different from those observed in ourpatient, but he
did have vertebral anomalies as seen in our patient. The other
cases were mosaic del(20)(pter!p12.2) in two patients who
had similar craniofacial dysmorphic features, severe mental
retardation and seizures [Fryns et al., 1992; Sauter et al.,
a: The rec(20)dup 20q (*) chromosome, (b) the inv(20)(p12q13.1)
(center), and the inv(20) chromosomes (right).
Ideograms showing the normal 20 (left), the rec(20)dup 20q
has two subtelomeric 20q signals (red) and no subtelomeric 20p signal
subtelomeric signal (red). [Color figure can be viewed in the online issue,
which is available at www.interscience.wiley.com.]
FISH with subtelomeric probes for chromosome 20. The rec(20)
310 Grange et al.
2003]. One of these patients also had autistic behavior [Sauter
et al., 2003].
It is interesting to note that the father of our patient, who
carries the inv(20)(p13q13.1), had a history ofpoor growth and
and has normal stature and intelligence. His mother report-
edly has six lumbar vertebrae, an abnormality seen in our
if she carries the same inversion as her son. The father has
not had X-rays of his spine, and thus it is unknown if he has
vertebral anomalies. It is possible that a gene related to
vertebral segmentation is disrupted at one of the breakpoints
of the inversion, either at 20p13 or 20q13.1.
Pericentric inversions of chromosome 20 are quite rare and
to our knowledge the breakpoints observed in the father of our
patient have not been reported before (Table II) [Jenderny
et al., 1992]. These inversions were often detected on prenatal
studies (6 of 11 cases). The others were observed in a man
whose wife had three spontaneous abortions, in a liveborn
infant with congenital anomalies, and in three cases ascer-
tained after the diagnosis of a recombinant in the offspring
[Lucas et al., 1985; Bown et al., 1986; present case].
The paternal pericentric chromosome inversion and the
occurrence of an abnormal recombinant of chromosome 20 in a
liveborn infant puts this family at risk to have other affected
liveborn offspring in future pregnancies. Using data from
counseled with an overall empiric recurrence risk of 5–10%
derived from several sources [Groupe de Cytogeneticiens
Francais, 1986; Sherman et al., 1986; Stene, 1986]. Combined
data from American, Canadian, and European prenatal
studies provides a slightly higher recurrence risk estimate of
10–15% for inversions with small distal segments in families
with a previously affected liveborn child [Daniel et al., 1989].
Recombinants of chromosome 20 are rare. The only two
1986]. With such a small sample it is not clear if there is an
ascertainment bias, a difference in viability between recombi-
nant types, or if the meiotic recombination favors the genera-
tion of a specific recombinant. Research studies to collect data
about recombinant types and frequency could be done in male
carriers of pericentric inversions using the in vitro sperm
penetration hamster assay [Martin et al., 1994] or FISH
analysis of decondensed sperm nuclei with subtelomeric
probes [Anton et al., 2002].
We thank the family for their interest and cooperation
during the study.
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TABLE II. Reported Pericentric Inversions of Chromosome 20
Boue and Gallano a
Lucas et al. 
Bown et al. 
Miller et al. a
Valvova and Demirev 
Jenderny et al. 
aPrenatally ascertained cases.
TABLE I. Phenotypic Features of Trisomy
Normal intrauterine growth
Low frontal hairline
Blocked tear ducts
Deeply set eyes
Upslanting palpebral fissures
Protruding upper lip
Chin skin creases
Thick scalp hair
Clinodactyly of fifth finger
Other hand/foot anomalies
Rib or vertebral anomalies
Malrotation of intestine
aPatients decribed by Addor et al., 2002; Plotner et al., 2002; Herens et al.,
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312 Grange et al.