European Review for Medical and Pharmacological Sciences

2015; 19: 3241-3245

Del(18)(q12.2q21.1) syndrome: a case report andclinical review of the literature
G. IMATAKA, Y. OHWADA, N. SHIMURA, S. YOSHIHARA, O. ARISAKA
Department of Pediatrics, Dokkyo Medical University School of Medicine, Mibu, Tochigi, Japan

Abstract. – The terminal deletion of thelong arm of chromosome 18 is relatively common among cytogenetic abnormalities, which
occur incidentally in approximately 1 in 40,000
live births. Proximal interstitial deletions of thelong arm of chromosome 18 are less frequent.
The critical region on chromosome 18 of thissyndrome is del(18)(q12.2q21.1) and has recently been recognized as a new clinical entity.
We describe a 8-year-old boy with developmental delay, obesity, and epilepsy, with characteristic facial anomalies in whom G-banding chromosome analysis revealed a unique karyotypeof 46, XY, del(18)(q12.2q21.1). The patient wasdiagnosed with interstitial deletion chromosome 18q-syndrome. He received weight control therapy from a medical dietitian. For hisepilepsy, he was administered oral carbamazepine at 4 mg/kg/day. At age six, he entereda special needs elementary school. After entering school, he often showed hyperkinesis, andwas diagnosed with attention deficit hyperactivity disorder with mild mental retardation. Because patients with only del(18)(q12.2q21.1)
have no serious associated malformations,
physicians should be aware that even adult patients may have 18q-syndrome.
Therefore, if epilepsy occurs in patients withminor facial anomalies, psychomotor retardation, obesity, and the possibility of 18q-syndrome with del(18)(q12.2q21.1) should be kept
in mind, and chromosome testing should beperformed.
Key Words:
18q-, 18q12.3, Interstitial deletion, Obesity, Epilepsy.

Introduction
Terminal deletion of the long arm of chromosome 18 is relatively common among cytogenetic
abnormalities, which occur incidentally in approximately 1 in 40,000 live births1. However,proximal interstitial deletions of the long arm ofchromosome 18 are less common2-6. The criticalregion on chromosome 18 for this syndrome isdel(18)(q12.2q21.1) and has recently been recognized as a new clinical entity of thedel(18)(q12.2q21.1) syndrome7,8. The interstitialdeletion 18q-syndrome is clinically characterized
by developmental delay, seizures, obesity, abnormal behavior, and minor facial anomalies including ptosis, bilateral epicanthus strabismus, shortand slightly down-slanting palpebral fissures, fullcheeks, etc1-14. To our best of knowledge, only
seven liveborn patients with interstitial deletion
restricted involving del(18)(q12.2q21.1) havebeen reported in the literature2-6. Here, we describe an 8-year-old boy with developmental delay, obesity, and epilepsy, with characteristic facial anomalies in a de novo del(18)(q12.2q21.1).
Case Report
The patient was born with a weight of 3,285 g
and height of 49.5 cm. His head and chest circumference were each 33.0 cm. His mother had one
previous normal delivery. Delivery at 39+ weeks
gestation was difficult, and he was diagnosed withthe meconium aspiration syndrome. At the time ofhis birth, his father and mother were 38 and 31
years of age, respectively. Although slight, mild
muscle hypotonia of his extremities was observed,signs of birth asphyxia were not noted at delivery.
Multiple minor facial anomalies such as ptosis,
short and slightly down-slanting palpebral fissures, and moon face with full cheeks were recognized. No significant defects, including heart, lungor brain, were noted. Concerning motor movement, he was able to sit at ten months of age, andcould walk while holding onto something at one
year and four months of age. He could speak several meaningful words at one year and six months.
Stridor was repeatedly heard from eight months,
and he was diagnosed with baby asthma at 11months. His motor development and asthma weremonitored after that.
When he was three years old, his physique
was revealed to be characterized by macrocephaly and obesity. His head circumference atCorresponding Author: George Imataka, MD; e-mail: geo@dokkyomed.ac.jp3241

G. Imataka, Y. Ohwada, N. Shimura, S. Yoshihara, O. Arisaka

the age of 2 years and 11 months was 53.5 cm(+2.56 SD). His stature and weight were 91.3 cm(-0.41 SD) and 16.0 kg (+1.5 SD), respectively(Figure 1). He was started on weight control therapy with a medical dietitian. One testicle wasfixed in the intraabdominal space. For his nonpalpable testicle, surgery was performed to correct the testicular fixation at three years and fourmonths. At that time, he could run and jump actively. His developmental intelligence quotient
index was 92, and his verbal intelligence quotient
index was 52; he was diagnosed with mild mental retardation. At age four years, his breathing
frequently ceased for durations of more than 20
seconds during his sleep, and he was diagnosed
with obstructive sleep apnea syndrome. Moreover, he experienced general tonic-clonic convul-sions several times in the middle of the nightwith no fever. A sleep-induced electroencephalogram exhibited multifocal spikes in both hemispheres of the centro-parietal area. Brain magnetic resonance imaging (MRI) yielded normal findings. Based on these results, he was diagnosed
with epilepsy and was started on oral administration of carbamazepine 4 mg/kg/day.
To explore the cause of his mild facial anomalies, obesity, infantile motor developmental delay and mild mental retardation, sleep apnea syndrome, epilepsy and other conditions, we performed several examinations. Blood and urine
screening tests showed normal data. High resolution and G-banding chromosome analysis (Figure 2) using peripheral lymphocytes was performed due to his many symptoms, which re-Figure 1. Cross-sectional growth chart curve with Japanese boy. The growth curve of his physique revealed over +2.0 SD
obesity after 8-years-of his age.

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Del(18)(q12.2q21.1) syndrome: a case report and clinical review of the literature

Figure 2. Chromosome analysis. G-banding metaphase chromosomes was carried out on short-term lymphocyte cultures using standard procedures. Chromosome analysis is at 850-resolution revealed 46,XY,del(18)(q12.2q21.1).

vealed a unique karyotype of 46, XY,del(18)(q12.2q21.1). Therefore, he was diagnosed with interstitial deletion chromosome 18psyndrome. Additional chromosomal analysis byspectral karyotyping (SKY) using 24-color
probes showed normal findings.
At age six years, he entered a special needs elementary school. His epilepsy and asthma werewell controlled with carbamazepine and pranlukast hydrate, respectively. After entering thespecial needs elementary school, he often
showed hyperkinesis and received a warningfrom his teacher that he did not listen while others were talking. He was diagnosed with attention deficit hyperactivity disorder with mild
mental retardation. Also, he was being followed
for nocturnal enuresis at eight years of age.

Discussion
Trisomy 18, 18p-syndrome, and 18q-syndrome
have been established as syndromes associatedwith chromosome 18 abnormalities. At least 100
cases of 18q-syndrome, based on a deletion inchromosome 18, have been reported15. Many reports of 18q-syndrome describe a simple terminal
deletion, but reciprocal translocations and a microdeletion of only 18q12.3 have also been reported 3,11,12,14. The breakpoint is often 18q21(OMIM#601808). Serious incomplete myelination of the brain, which is seen in many cases of
18q-syndrome, is due to an abnormality of the18q23-MBP gene9,10.
Growth hormone deficiency is associated with
haplo insufficiency of the MBP or GALR1
gene16. This is a contiguous gene syndrome with

haplo insufficiency of a gene with a deleted region. Occasionally, part of a chromosome of unknown origin adheres to the 18q deleted region.
In such cases, an attempt to identify the unknown
region by G-band chromosome analysis of theparents, or spectral karyotyping (SKY), a special
fluorescence in situ hybridization (FISH) technique with differential staining of all chromosomes is necessary17,18.
On the other hand, interstitial deletions of thelong arm of chromosome 18 are rare, and thephenotype depends on the deleted region. Amonginterstitial deletions, case reports ofdel(18)(q12.2q21.1) are increasing, and thedel(18)(q12.2q21.1) syndrome is now recognized
as a new clinical entity. Only seven cases ofdel(18)(q12.2q21.1) syndrome have been reported to our knowledge (Table I)2-6. Patients witheven larger deleted regions, includingdel(18)(q12.2q21.1), have also been reported ashaving the del(18)(q12.2q21.1) syndrome. However, with abnormalities of the 18q23-MBP genewith even larger deleted regions, clinical findings, including severe mental retardation, differ
depending on the deleted region. Therefore,
Table I lists cases where the deleted region islimited to del(18)(q12.2q21.1) 2-6.
As shown in Table I, in 18q-syndrome, whendel(18)(q12.2q21.1) is the only deleted region,common clinical features include minor facial
anomalies, delayed motor and speech development, hypotonia, obesity, and epilepsy2-6. Moreover, 18q-syndrome, when del(18)(q12.2q21.1)
is the only deleted region, is characterized by theabsence of serious heart, lung, or brain complications. The oldest reported patient with 18q-syndrome involving only del(18)(q12.2q21.1) was a3243

3244

Term
ND
ND

ND++++ND

BirthWeek
LengthWeight

Facial anomaly
Strabismus
Epicanathus
Deep set eyes

Abnormal behavior
Developmental delay
Seizures
Hypotonia
2y 8m
95 cm
15 kg

ND++++++

Term
48 cm
2690 g

MaleND(q12.2q21.1)

Engelen JJ et al(1998)3

M = mother, F = father, ND = no data, y = year, m = months

Last examination (y.m.)
67yHeight150 cmWeight72.5 kg

FemaleND(q12.2q21.1)

Sex
Parents age M/FDeletion (18)

Tinkle BT et al(2003)2

4y 11m100 cm16.5 kg

++++

ND+
ND

ND
ND
ND

Female24/26(q12.2q21.1)

Schinzel A et al(1991, case 1)42y 5m
ND18.7 kg

ND++++ND
ND

Term
ND
3010 g

MaleND(q12.2q21.1)

Schinzel A et al(1991, case 2)44y 10m
108 cm
20 kg+++
ND++ND

3750 cm
2600 gMale
ND(q12.2q21.1)

Schinzel A et al(1991, case 3)4

Table I. Clinical features in the reviews of reported 8 cases with non-mosaic of del(18)(q12.2q21.1) syndrome.

7y134 cm
59.5 kg++++ND++

Term
51 cm
4600 gMale
32/34(q12.2q21.1)

1y 8m
84 cm
12.2 kg+++++++Term52 cm2880 gFemale
27/35(q12.2q21.1)

Wilson MG et al Kotzot D et al(1989)5(2005)68y 7m
131 cm38.5 kg+++++++

3949.5 cm
3285 gMale31/38(q12.2q21.1)

Our case(2015)

G. Imataka, Y. Ohwada, N. Shimura, S. Yoshihara, O. Arisaka

Del(18)(q12.2q21.1) syndrome: a case report and clinical review of the literature

67-year-old woman2, thus indicating that longterm survival is fully possible. Epilepsy, which isseen in all cases, can be treated with conventional anti-epileptic drugs, and no intractable epilepsy has been reported and one had intractableepilepsy13.
Because patients with only del(18)(q12.2q21.1)
have no serious associated malformations, physicians should be aware that even adult patients
may have 18q-syndrome. Therefore, if epilepsy
occurs in patients with minor facial anomalies,
psychomotor retardation, and obesity, the possibility of 18q-syndrome with del(18)(q12.2q21.1)
should be kept in mind, and chromosome testingshould be performed.

7)

8)

9)

10)

11)

–––––––––––––––––-––––
Conflict of InterestThe Authors declare that there are no conflicts of interest.
12)

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