EXPERIMENTAL AND THERAPEUTIC MEDICINE 13: 3494-3496, 20173494

Rare de novo inversion-duplication case with pure
3qter duplication syndrome including an overlapof the dup(3q) critical region: A case report
GEORGE IMATAKA1, YOSHIYUKI WATABE1, SAYURI KAJITANI1, SHUN WATANABE2,JUNKO ICHIKAWA1, FABRIZIO DRAGO3, HIROSHI SUZUMURA1 and SHIGEMI YOSHIHARA11Department of Pediatrics and 2First Department of Surgery, Dokkyo Medical University, Tochigi 321-0293, Japan;
Department of Pediatric Cardiology and Cardiac Surgery, Pediatric Cardiology and Cardiac Arrhythmias Complex Unit,Bambino Gesù Children's Hospital and Research Institute, I-00050 Rome, Italy

3

Received March 8, 2017; Accepted April 18, 2017
DOI: 10.3892/etm.2017.4416
Abstract. We report here a very rare case of de novo
inversion-duplication chromosomal abnormality with a pure
3qter duplication syndrome. Interestingly, the 3q duplication
includes an overlap of the syndrome's critical region. Although
there have only been 9 cases of this syndrome reported in thepast, our patient had more severe neurological abnormalities
than anticipated. In this regard, we have gathered the 3q chromosomal duplication abnormalities known to cause pure 3q
duplication syndrome to date as a reference for comparisonsand we discuss the particulars of our case.
Introduction
Pure chromosome 3q duplications are very rare. Most of thereported cases with a 3q duplication syndrome are thought tooccur from parental unbalanced translocations (1). Here we
report the case of a little girl with a very rare chromosomal
abnormality consisting of pure duplication of 3qter due to amechanism of de novo inversion(3)-duplication and its associated clinical syndrome.
Case report
The mother of the unborn baby had been hospitalized since themiddle of her pregnancy due to premature labor risk signs. Thefetus was diagnosed with ventricular enlargement by ultrasonicexamination. The female neonate was born through vaginal
delivery at 31 weeks and 2 days of the maternal pregnancy.
Her birth weight was 1,308 g. Asphyxia was noted at birth.

Correspondence to: Dr George Imataka, Department of Pediatrics,

Dokkyo Medical University, 880 Kitakobayashi, Shimotsuga, Mibu,
Tochigi 321-0293, Japan
E-mail: geo@dokkyomed.ac.jp

Key words: 3q, duplication syndrome, congenital anomaly

Also, multiple anomalies were recognized at birth including
hypertelorism, wide nasal bridge, micrognathia, cleft palateand lips, low-set ears and dysmorphic fingers. A large softhemangioma was localized on the occipital region of the head.
Cardiac ultrasonography confirmed a ventricular septal defectmuscular region of 2 mm in diameter. The baby also presented
congenital hearing loss confirmed by tests. Oral feeding withmilk was difficult due to stenosis of the throat and the tonguesettlement, and it became necessary to provide the infant witha feeding tube. Unfortunately, aspiration pneumonia associated with gastro-esophageal reflux occurred and the infant had
to be placed under long term-artificial ventilation therapy.
At the time, the parents were provided genetic counseling;
after which chromosomal examination revealed the infant's
karyotype as 46 XX, dup(3)(q29q22) (Fig. 1). Motor and intellectual developments were delayed and at 6-months of age, theinfant was still unable to stabilize her head and neck in theupright position. Brain magnetic resonance imaging (MRI)
showed evidence of delayed myelination and agenesis of thecorpus callosum (Fig. 2). No further abnormalities were noted
until the little girl became two years old, then a diagnosis ofdevelopmental retardation was given and a gastrostomy line
had to be established for her daily nutrition.
Discussion
There are three types of mechanisms by which 3q partial
trisomy occurs. In one, an inversion(3) in a parent's chromosome 3q becomes the recombinant chromosome. In another,
the defect is caused by a parental unbalanced translocation.
And finally, a last possible mechanism involves partial chromosome duplication with de novo-inversion. In recombinant
chromosomes with translocations, there are many cases
where partial monosomy by a chromosome different fromthat involved in the partial trisomy chromosome is alsopresent. Many of the papers previously reported on 3q trisomy
syndrome included partial monosomies in chromosomes otherthan the 3q chromosome involved in the partial trisomy (1).
Our case is special in that the 3q partial trisomy is caused
only by de novo 3q inversion-duplication. The chromosomal

IMATAKA et al: PURE DUPLICATION 3q3495

Figure 1. Chromosomal analysis with high resolution band stain, employing fifteen cells. Stain band level is 550. The karyotype of the patient revealed
dup(3)(q29q22).

Figure 2. Sagital MRI image of the 6-month-old patient showing delayed
myelination, agenesis of the corpus callosum and non-involuting congenital
posterior hemangioma. Spin echo method (echo time, 13.00 msec; repetitiontime, 700.00 msec) T1-weighted sagittal brain MRI. MRI, magnetic resonance imaging.

Figure 3. Overview of the chromosomal abnormalities in all the reported
pure 3q duplication syndrome cases found. A critical region of 3q duplication
at the chromosomal 3q26.31-q27.3 region is essential for the characteristic
clinical phenotype.

karyotype of our patient is 46 XX, dup(3)(q29q22), which
can be classified as a pure 3q duplication (since it does not
involve excess or deficiency of other chromosomal fragments).
Our report is a very valuable source of information for theclinical syndrome resulting from pure 3q duplication, given
the scarcity of such cases. Furthermore, the etiology of manyof the reported 3q duplication syndromes is duplication of3q21→qter, and to the best of our knowledge only 9 individuals
with pure 3q duplication syndrome have been reported in theliterature (2-9). Our case represents the 10th case; Fig. 3 for agraphic comparison of the partial 3q trisomy in our case withthe others available. In pure 3q duplication syndrome, it is notnecessary to consider the monosomy of another chromosomal
fragment when analyzing the etiology of phenotypic clinical

3496

EXPERIMENTAL AND THERAPEUTIC MEDICINE 13: 3494-3496, 2017

features. Thus, careful comparison of the clinical featuresdescribed in other pure 3q duplications can help elucidate theinfluence of specific gene critical regions on the phenotype.
Faas et al reported a de novo 3q duplication syndrome withdescriptions of 6 other previous cases and concluded that a
critical region responsible for the 3q duplication phenotype
could be assigned to 3q26.31-q27.3 (7). In this study, our case
was analyzed in view of the previous reports; our 3q partial
trisomy overlaps with the described critical region on chromosome 3. Moreover, the severity of the motor and intellectualdeficiencies in our case is uncommon. This may be due to thespecific chromosomal fragments involved in the inversionduplication in our case when compared to the syndromes
described in past reported cases (2-8). More cases should be
examined in the future in order to fully understand the characteristics of pure 3q duplication syndrome.
References
1. Koç A, Ekmekci AY and Ozer O: A case of dup(3q) syndrome.
Genet Couns 24: 381-385, 2013.
2. Wilson GN, Hieber VC and Schmickel RD: The association ofchromosome 3 duplication and the Cornelia de Lange syndrome.
J Pediatr 93: 783-788, 1978.

3. Stengel-Rutkowski S, Murken JD, Pilar V, Dutrillaux B,Rodewald A, Goebel R and Bassermann R: New chromosomal
dysmorphic syndromes. 3. Partial trisomy 3q. Eur J Pediatr 130:111-125, 1979.
4. Sciorra LJ, Bahng K and Lee ML: Trisomy in the distal end of
the long arm of chromosome 3. A condition clinically similar to
the Cornelia de Lange syndrome. Am J Dis Child 133: 727-730,
1979.
5. Rosenfeld W, Verma RS, Jhaveri RC, Estrada R, Evans H,Dosik H and Opitz JM: Duplication 3q: severe manifestations in
an infant with duplication of a short segment of 3q. Am J Med
Genet 10: 187-192, 1981.
6. van Essen AJ, Kok K, van den Berg A, de Jong B, Stellink F,Bos AF, Scheffer H and Buys CH: Partial 3q duplication
syndrome and assignment of D3S5 to 3q25-3q28. Hum Genet 87:151-154, 1991.
7. Faas BH, De Vries BB, Van Es-Van Gaal J, Merkx G, Draaisma JM
and Smeets DF: A new case of dup(3q) syndrome due to a pureduplication of 3qter. Clin Genet 62: 315-320, 2002.
8. Meins M, Hagh JK, Gerresheim F, Einhoff E, Olschewski H,Strehl H and Epplen JT: Novel case of dup(3q) syndrome due
to a de novo interstitial duplication 3q24-q26.31 with minimal
overlap to the dup(3q) critical region. Am J Med Genet A 132A:84-89, 2005.
9. Shanske AL, Leonard J, Nahum O, Coppock DL and Levy B:
Delineation of the breakpoints of pure duplication 3q due toa de novo duplication event using SOMA. Am J Med GenetA 152A: 3185-3188, 2010.