CLINICAL REPORT

Familial Ring (18) Mosaicism in a 23-Year-Old

Young Adult With 46,XY,r(18) (::p11!q21::)/46,XY
Karyotype, Intellectual Disability, Motor Retardation
and Single Maxillary Incisor and in His
Phenotypically Normal Mother, Karyotype
47,XX,þr(18)(::p11!q21::)/46,XX
Sevim Balci,1* Celal T€umer,2 Çigdem Karaca,2 and Oliver Bartsch3
1
Department of Clinical Genetics, Ihsan Dogramacı Children’s Hospital, Hacettepe University, Ankara, Turkey
2
Department of Oral and Maxillofacial Surgery, Faculty of Dentistry, Hacettepe University, Ankara, Turkey
3
Institut f€ur Humangenetik, Universit€atsmedizin der Johannes Gutenberg–Universit€at Mainz, Mainz, Germany

Received 15 July 2010; Accepted 24 November 2010

We report on a 23-year-old man with craniofacial findings of the
holoprosencephaly spectrum disorder (microcephaly, hypote-
lorism, depressed nasal bridge, single median maxillary central
incisor), fusion of C2–C3 vertebrae, intellectual disability, and
severe sleep apnea. Chromosome analysis of blood lymphocytes
showed 75% ring (18) cells and 25% normal cells, karyotype mos
46,XY,r(18)(::p11!q21::)[75]/46,XY[25]. His mother was phe-
notypically normal except for a double ureter and bifid renal
pelvis as in his son. She had a supernumerary ring (18) in 10% of
blood lymphocytes, karyotype mos 47,XX,þr(18)(::p11!q21::)-
[10]/46,XX[90]. Familial ring (18) is a rare cytogenetic abnor-
mality. This is the first report of a mother with a supernumerary
ring (18) and a son with ring (18) mosaicism. Interestingly, the
son showed a true mosaicism (mixoploidy) of ring (18) and
normal cells. The mother’s 46,XX cells could be easily explained
by mitotic instability and ring loss during cell division. However,
the coexistence of ring (18) and normal cells in the son is unusual.
Possibly, during early postzygotic divisions of a 47,XY,þr(18)
zygote, two (possibly subsequent) genetic events could have
occurred, one when one normal chromosome 18 was lost
(resulting in a cell line with ring 18), and one when the ring
18 was lost (resulting in a cell line without ring, ‘‘escape to
normal’’). Alternatively, the zygote of the son could have been
46,XY,r(18), and postzygotic loss of the ring 18 could have
resulted in monosomy 18 cells followed by duplication of chro-
mosome 18 in these cells (a rare mechanism for cell survival
previously described as ‘‘compensatory’’ isodisomy).

2011 Wiley-Liss, Inc.
Key words: familial mosaic ring chromosome 18; ring chromo-
some 18; supernumerary ring 18; single median maxillary central
incisor (SMMCI)
How to Cite this Article:
Balci S, T€
umer C, Karaca Ç, Bartsch O. 2011.
Familial ring (18) mosaicism in a 23-year-old
young adult with 46,XY,r(18) (::p11!q21::)/
46,XY karyotype, intellectual disability,
motor retardation and single maxillary
incisor and in his phenotypically normal
mother, karyotype
47,XX,þr(18)(::p11!q21::)/46,XX.
Am J Med Genet Part A 155:1129–1135.
INTRODUCTION
Ring chromosome 18 is one of the more frequent ring chromo-
somes [Kosztolanyi et al., 1991] and most individuals with kar-
yotypes of 46,XX or XY,r(18) show phenotypes resulting from
deletions of the distal chromosomes 18p and 18q. The chromosome
18p and the chromosome 18q deletion syndromes (OMIM 146390
and 601808, respectively) may also arise from other chromosome
abnormalities (in many cases, translocations) and have been re-
ported with a wide spectrum of clinical abnormalities [Linnankivi
et al., 2006; Turleau, 2008]. Accordingly, there have been excep-
tional reports of familial transmission of 18p and 18q deletions, in
*Correspondence to:
Sevim Balci, Department of Clinical Genetics, Ihsan Dogramacı Children’s
Hospital, Hacettepe University, Zirvekent, 2 Etap, C Blok, Kat 8 Daire 35,
Birlik Man, Gankaya, Ankara, Turkey. E-mail: sbalci@hacettepe.edu.tr
Published online 11 April 2011 in Wiley Online Library
(wileyonlinelibrary.com).
DOI 10.1002/ajmg.a.33868

2011 Wiley-Liss, Inc. 1129

1130 AMERICAN JOURNAL OF MEDICAL GENETICS PART A

most cases from a mildly affected mother to her child [Velagaleti

et al., 1996; Tsukahara et al., 2001; Chen et al., 2006; Linnankivi
et al., 2006; Maranda et al., 2006]. In addition, there have been at
least seven reports of familial transmission of ring chromosome 18
[Kosztolanyi et al., 1991; Fryns et al., 1992; Jenderny et al., 1993].
Single median maxillary central incisor (SMMCI) is an unusual
dental abnormality occurring in 1 out of 50,000 births [Hall,
2006]. SMMCI has been reported as an isolated finding or associ-
ated with midline developmental defects, in particular associated
with holoprosencephaly (HPE) and its microforms [Solomon et al.,
2010]. HPE spectrum disorder is one of the most common devel-
opmental anomalies of the human brain and is associated with
cylopia, absence of nose and agnathia or absence of the mandible
[Balcı et al., 1993; Kauvar et al., 2010]. Etiologically, HPE and
SMMCI may be due to chromosomal abnormalities, monogenic
mutations, or environmental factors. Various genes for HPE have
been identified including the TGIF gene (formerly named as HPE4
FIG. 1. (a) The patient at age 9 months, note deciduous single
locus) on chromosome 18p [Gripp et al., 2000]. HPE and SSMCI
maxillary incisor, (b) permanent single maxillary incisor at adult
are long known to represent seminal clinical signs of the ring
age, and (c) facial appearance of the patient at age 9 years, note
chromosome 18 syndrome, and have been shown to result from round face, hypotelorism, small nose, very hypoplastic columella
haploinsufficiency of the TGIF gene residing on chromosome 18p nasi, prominent chin, and cupped ears with large lobes. [Color
only 3.4 Mb from the telomere [Gripp et al., 2000]. figure can be viewed in the online issue, which is available at
Here, we report on a normal mother with partial trisomy 18 www.wileyonlinelibrary.com]
caused by a ring chromosome 18 [mos 47,XX,þr(18)/46,XX] and
resulting in a 46,XY,r(18)/46,XY mosaicism in her son with
SMMCI, intellectual disability and severe sleep apnea. Familial
transmission of ring chromosome 18 has been reported, but there system continuing as a single ureter at the level of the iliac artery
has been no previous reports of mosaicism of a ring chromosome 18 (Fig. 2a). Growth hormone was decreased at 0.6 ml U/ml (normal
with normal cells, 46,XY,r(18)/46,XY, in the offspring. 0–20) and somatomedin-C was increased at 1,148 ng/ml (normal
90–270).
At age 17 years the patient was readmitted because of severe sleep
CLINICAL REPORT apnea. Paranasal sinus CT showed a deviation of the nasal septum to
The patient was the second child of healthy Turkish parents, a 31- the right, narrow nasal cavity, mandibular prognathism, and fusion
year-old mother and a 35-year-old father. His parents were first of cervical vertebrae at the level of C2–C3 (Fig. 2b). When last seen
cousins. His older sister was healthy. Family history was unremark- at the age of 23 years, he suffered from severe sleep apnea, obesity,
able. He was born by caesarean; birth weight was 2,250 g (<3rd and idiopathic leg edema treated with antidiuretics. Height was
centile) and length was 42 cm (<3rd centile). He was first seen 155 cm (<3rd centile) and weight was 90 kg (>97th centile). He was
by one of us (S.B.) at the age of 9 months and was seen almost cognitively impaired, but was well-mannered and very cooperative
every year for until 23 years of age. Positive clinical findings at with a friendly attitude.
9 months included hypotonia, motor retardation, microcephaly Recently, we asked for the photos of patient and his mother. The
(occipitofrontal circumference [OFC] 42 cm; <3rd centile), hypo- facial appearance of patient was characterized by short neck, round
telorism, depressed nasal bridge, underdeveloped alae nasi, very face and microcephaly (Fig. 3a) and facial picture of patient with
hypoplastic columella, smooth philtrum, deciduous single median open mouth is characterized by single maxillary incisor, small nose
maxillary central incisor (SMMCI) (Fig. 1a), bilateral clinodactyly, with hypoplastic alae nasi (Fig. 3b). This facial appearance is
and cryptorchidism. His length was at the 10th centile (68 cm), and compatible with HPE spectrum. The facial picture of the mother
his weight was at the 50th centile (8.5 kg). Developmental screening was normal. Her head circumference was 54 cm, i.e., normal. There
examinations indicated a developmental quotient of 70 at age was no hypotelorism and she had a normal nose (Fig. 4). The
3 years and intellectual disability (IQ 44) with autistic features at intelligence of the mother is normal.
age 6 years. At age 9 years findings included short stature at 125 cm Clinical findings of the patient and his mother are summarized in
(<3rd centile), normal weight (21.5 kg; 10th centile), and micro- Table I.
cephaly (OFC 49 cm; <3rd centile). He had a permanent SMMCI
(Fig. 1b), long cupped ears with large lobes, and short neck (Fig. 1c).
He also had small penis, cryptorchidism, and flat feet. Cranial CYTOGENETIC STUDIES AND FLUORESCENCE IN SITU
computed tomography (CT) demonstrated frontotemporal atro-
phy and a large cisterna magna. An intravenous pyelogram (IVP)
HYBRIDIZATION (FISH)
showed a bifid pelvis on the left kidney; his mother was also found to Cytogenetic and FISH analyses were performed using conventional
have a bifid pelvis on the left kidney along with a double collecting techniques and lymphocytes from the patient, his mother, his
BALCI ET AL. 1131

FIG. 2. (a) Intravenous pyelogram of the mother, note bifid pelvis of left kidney and double collecting systems continuing as single ureters at the level
of the iliac artery. The patient also had bifid pelvis of left kidney. (b) Paranasal sinus CT of the patient, lateral section, note mandibular prognathism
and cervical vertebrae fusion at C2–C3.

father, and his sister. The chromosome analyses of the father and
sister were normal.
In the patient, G-banding analysis of metaphases at age 9 years
showed 75 cells (75%) with a ring (18) (Fig. 5) and 25 cells (25%)
with a normal 46,XY karyotype (not shown). Metaphase FISH
analysis (Fig. 6) was performed at age 17 years using a total of
four different DNA probes; the alphoid 18 centromere (cen)
probe D18Z1 (P5041; purchased from Appligene/Oncor, Illkirch,
France), BAC 248E24 containing the BCL2 gene or parts thereof
(18q21.33), CEPH YAC 957g7 (D18S466/D18S1092/D18S61;
18q22.1-q22.2), and CEPH YAC968f4 (D18S488; 18q22.3), respec-
tively. Using the 18cen probe, 30 metaphases were evaluated, of
which 11 (37%) showed a ring (18) and a normal 18, inferred
karyotype 46,XY,r(18), and 17 (57%) showed two normal chro-
mosomes 18, inferred karyotype 46,XY. Two metaphases (6.7%)
displayed only one normal 18, but chromosome numbers could not

FIG. 3. The patient at age 23 years, note (a) microcephaly, round face, and short neck and (b) small nose with hypoplastic alae nasi and single
maxillary incisor. These signs are indicative of a HPE spectrum disorder. [Color figure can be viewed in the online issue, which is available at
www.wileyonlinelibrary.com]
1132
FIG. 4. The mother of the patient, note normal facial appearance,
absence of hypotelorism, and normal nose. Her intelligence was
normal in spite of 10% cells with r(18) in blood. [Color figure can be
viewed in the online issue, which is available at
www.wileyonlinelibrary.com]
be counted and therefore, we could not determine whether these
metaphases represented preparational artifacts, or cells with mono-
somy 18 due to loss of the ring (18). Five metaphases were analyzed
with each probe BAC 248E24, YAC 957g7, and YAC968f4, and these
loci were found to be present on the normal 18 and absent on the
ring (18), locating the breakpoint on 18q proximal of the BCL2
gene, and by size of the ring chromosome most likely within 18q21.
FISH results in the patient are summarized in Table II. His karyo-
type after FISH was 46,XY,r(18).ish r(18)(::p11!q21::)(D18Z1þ,
BCL2,D18S466/D18S1092/D18S61,D18S488)[11]/45,XY,-18.
ish 18(D18Z1x1)[2]/46,XY.ish 18(D18Z1x2)[17].
In the mother, G-banding analysis of metaphases showed 90
normal cells (90%) and 10 cells (10%) with the supernumerary ring
(18) chromosome. Metaphase FISH analysis was performed using a
whole chromosome paint for 18 (wcp18; purchased from Vysis,
Downers Grove, IL). The ring was fully painted (not shown), and
therefore was made up of chromatin from 18, but not from other
chromosomes. Systematic analysis of 50 metaphases showed 47
cells (94%) with normal 18s and 3 metaphases with only one normal
18 (for explanation, see FISH section of patient).
DISCUSSION
Ring chromosome 18 is not a rare cytogenetic finding, but familial
transmission of ring chromosome 18 has been reported rarely
[Kosztolanyi et al., 1991; Fryns et al. 1992; Jenderny et al., 1993];
this only the second report of a supernumerary ring (18) in a parent
and a ring (18) in the offspring [Jenderny et al., 1993]. The
AMERICAN JOURNAL OF MEDICAL GENETICS PART A
phenotypically and mentally normal mother had transmitted the
ring chromosome 18 to her son. Most likely the mosaicism in the
mother originated from a rescue of a trisomic zygote generating
normal diploid cell lines through mitotic non-disjunction events.
The daughter described by Jenderny et al. [1993] showed a 46,XX,r-
(18) karyotype with a monocentric ring and the breakpoints
approximately at p11 and q23 in all 100 lymphocytes studied. In
contrast, the son in this report had a very interesting mosaicism of
46,XY,r(18) cells (37%, see FISH analysis section) and apparently
normal cells (57%), which is unique compared to other reports
on inherited ring chromosomes. The perplexing observation of a
(single) cell with a normal female chromosome complement in a
girl with familial ring (19) chromosome mosaicism has previously
been reported and discussed [Flejter et al., 1996].
The mother’s germ cell must have contained the r(18), and we
assume that her haploid set most likely was 24,X,þr(18). Accord-
ingly, the zygote of her son was set up as 47,XY,þr(18). During the
postzygotic divisions, two (possibly subsequent) genetic events
could have occurred, one when one normal chromosome 18 was
lost (resulting in a cell line with ring 18), and one when the ring 18
was lost (resulting in a cell line without ring, ‘‘escape to normal’’).
Alternatively, the zygote of the son could have been 46,XY,r(18);
postzygotic loss of the ring 18 could have resulted in monosomy 18
cells followed by duplication of chromosome 18 in these cells (a rare
mechanism for cell survival named ‘‘compensatory’’ isodisomy)
[Petersen et al., 1992; Bartsch et al., 1994]. DNA for studies of
uniparental isodisomy and cells from other tissues (fibroblasts) for
further cytogenetic studies were not available.
Table I summarizes the clinical findings in the patient and his
mother. Most abnormalities can be attributed to the distal mono-
somy 18p of the patient (Table I). In its most common form, the
18p-syndrome is nonspecific. In general the size of the deletions
correlate severity of the phenotype. The main clinical features
include short stature, round face with short philtrum, hypotelor-
ism, and palpebral ptosis (as microforms of the holoprosencephaly
[HPE] spectrum disorder), and large ears. Intellectual disability is
usually mild to moderate, but only some 10–15 percent of patients
present with more severe dental, facial and brain malformations
clearly indicating a HPE spectrum disorder. This patient demon-
strated unequivocal features of the HPE spectrum including hypo-
telorism and deciduous and permanent SMMCI, although the
cranial imaging (CT, MRI) did not show overt holoprosencephaly.
The signs of holoprosencephaly in the 18p-syndrome are explained
by the haploinsufficiency of the TGIF1 gene (HPE4 locus) on
chromosome 18p11.31, which resides at 3.4 Mb from the 18p
telomere and must be deleted in this patient. Deletion of distal
chromosome 18p are among the most common chromosomal
changes found in patients with HPE [Roessler and Muenke,
2010]. The penetrance of 18p deletions as a cause of HPE is low
(approximately 10–15%), suggesting that this is a weak HPE
locus and that additional genetic or environmental factors, such
as low retinoids, may be required for manifestation [Roessler and
Muenke, 2010].
The breakpoints on this ring chromosome were crudely mapped
in the year 2000 using FISH and a limited supply of cytogenetic
slides. Five loci or probes could be studied. First, the ring was
unequivocally confirmed as a ring (18) by use of an alphoid probe
 BALCI ET AL.

TABLE I. Clinical Findings in the Patient and His Mother, and Frequent Clinical Findings in the Distal Monosomy 18p and Distal Monosomy 18q Syndromes, Respectively
Frequent clinical findings with
Frequent clinical findings with monosomy monosomy 18q23!qter
This patient Mother of this patient 18pter!p11.2 (OMIM 146390) (OMIM 601808)
46,XY,r(18)(::p11!q21::)/46,XY 47,XX,þr(18)(::p11!q21::)/46,XX
Short stature (final height 155 cm, <3rd centile) Normal stature Short stature Short stature
Moderate mental retardation (IQ 44 at age 6 years) Normal Mild to moderate mental retardation Mild to moderate mental retardation
Autistic behavior Normal Autistic behavior
Microcephaly Normal (54 cm) Microcephaly Microcephaly
Round face with smooth philtrum Round face with short philtrum Short philtrum
Hypotelorism, flat nasal bridge, small nose, Normal Holoprosencephalyspectrum disorder in Flat nasal bridge
hypoplastic alae nasi, very hypoplastic columella about 10% of cases
Single median maxillary central incisor (SMMCI) Normal Single median maxillary central incisor
Cupped ears with large lobes Normal Large protruding ears with detached pinnae Prominent antihelix and antitragus,
narrow or atretic external canal
Mandibular prognathism Normal Micrognathia Mandibular prognathism
Short neck, cervical vertebral fusion C2/C3 Normal Kyphoscoliosis Short neck, extra ribs
Bifid pelvis on left kidney Bifid pelvis on left kidney, — Occasional abnormality:
double collecting systems horseshoe kidney
continuing as a single ureter
at the levels of the iliac artery
Cryptorchidism Normal Cryptorchidism Cryptorchidism
Cranial MRT: microcephaly, non-specific lesions of — Cranial Imaging: Holoprosencephaly Cranial Imaging: white matter
white matter, holoprosencephaly was ruled out. spectrum disorder in about 10% of cases abnormalities, enlarged ventricles
Cranial CT: frontotemporal atrophy, large
cisterna magna
IgA normal at 135 mg/dl at the age of 9 years — — Low levels of immunogobulin A (IgA)
(reference range 29–270)
1133
1134 AMERICAN JOURNAL OF MEDICAL GENETICS PART A

FIG. 5. Partial karyotypes of (a) patient and (b) mother.

FIG. 6. Results by FISH, (A) partial metaphase of the patient hybridized with alphoid DNA probe D18Z1 (chromosome 18cen), note two normal FISH
signals, one on the normal homologue 18 (white arrow) and the other on the ring(18) (gray arrow), proving that the ring represents a ring 18, and (B)
metaphase of the patient hybridized with BAC bC248E24 (BCL2 gene area, chromosome 18q21.33), note FISH twin spot signals present on the
normal homologue 18 (white arrow) and absent on the ring 18 (gray arrow), locating the breakpoint on 18q proximal of the BCL2 gene. [Color figure
can be viewed in the online issue, which is available at www.wileyonlinelibrary.com]

TABLE II. Positions of DNA Probes Used for FISH Analyses and Results in the Patient
DNA probe Positiona Genes and markers Chromosome Result
Appligene/Oncor P5041 15,400,000–19,000,000 D18Z1 18cen x2, signal present on ring 18
BAC 248E24 60,790,579–60,987,361b BCL2 18q21.33 x1, signal absent on ring 18
YAC 957g7 66,424,036–67,439,275b D18S466/D18S1092/D18S61 18q22.1-q22.2 x1, signal absent on ring 18
YAC 968f4 69,404,487–69,404,723b D18S488 18q22.3 x1, signal absent on ring 18
a
Position on chromosome 18 in bp according to the Ensembl genome browser, release 58, data compiled on 6 July 2010 (http://www.ensembl.org/). The TGIF1 gene is located on chromosome
18p11.31 at 3,412,072–3,458,409 bp.
b
Data indicate positions of markers within DNA probes.
BALCI ET AL.
for the chromosome 18 centromere (Fig. 4b) and whole chromo-
some 18 painting. Cytogenetically, the breakpoint on the long arm
had been tentatively placed in or near 18q22.2, but FISH using three
different YAC and BAC clones (representing 18q22.3, 18q22.2-22.1,
and 18q21.3), respectively, yielded no signals on the ring (18),
indicating deletion of these regions and placing the breakpoint
between the BCL2 gene, which resides in 18q21.3 (deleted), and the
18 centromere (Fig. 4a, Table II).
In summary we report on mosaic (10%) additional ring chro-
mosome 18 in a mother and the presence of the ring as constitutive
member of the chromosome set in 90% of her son’s lymphocytes.
The mother intelligence and phenotype is normal. This family is the
second familial mosaic ring 18 in the literature.
ACKNOWLEDGMENTS
We wish to thank the family for consenting to this study and Mrs.
Diana Villwock for assistance with the manuscript.
We are very appreciated the family of the patient for cooperation
since 1999. Thanks again the family and especially the patient’s
mother.
REFERENCES
Balcı S, Onol B, Ercal MD, G€ unay M, Besim A, Eryılmaz M. 1993.
Autosomal recessive alobar holoprosencephaly with cylops in three
females sibs prenatal ultrasonographic diagnosis at 18th week. Clin
Dysmorph 2:165–168.
Bartsch O, Petersen MB, Stuhlmann I, Mau G, Frantzen M, Schwinger E,
Antonarakis SE, Mikkelsen M. 1994. ‘‘Compensatory’’ uniparental
disomy of chromosome 21 in two cases. J Med Genet 31:534–540.
Chen CP, Lin SP, Chern SR, Lee CC, Huang JK, Wang W. 2006. Direct
transmission of the 18q-syndrome from mother to daughter. Genet
Couns 17:185–189.
Flejter WL, Finlinson D, Root S, Nguyen W, Brothman AR, Viskochil D.
1996. Familial ring (19) chromosome mosaicism: case report and review.
Am J Med Genet 66:276–280.
1135
Fryns JP, Kleczkowska A, Smeets E, Van Den Berghe H. 1992. Transmission
of ring chromosome 18 46, XX/46,XX,r(18) mosaicism in a mother and
ring chromosome 18 syndrome in her son. Ann Genet 35:121–123.
Gripp KW, Wotton D, Edwards MC, Roessler E, Ades L, Meinecke P,
Richieri-Costa A, Zackai EH, Massague J, Muenke M, Elledge SJ. 2000.
Mutations in TGIF cause holoprosencephaly and link NODAL signalling
to human neural axis determination. Nat Genet 25:205–208.
Hall RK. 2006. Solitary median maxillary central incisor (SMMCI)
syndrome. Orphanet J Rare Dis 1:12.
Jenderny J, Caliebe A, Beyer C, Grote W. 1993. Transmission of a ring
chromosome 18 from a mother with 46,XX/47,XX,þr(18) mosaicism to
her daughter, resulting in a 46,XX,r(18) karyotype. J Med Genet 30:
964–965.
Kauvar EF, Solomon BD, Curry CJR, VanEssen AJ, Jansseu N, Dutra A,
Roessler E, Muenke M. 2010. Holoprosencephaly and agnathia spectrum:
Presentation of two new patients and review of the literature. Am J Med
Genet Part C 154C:158–159.
Kosztolanyi G, Mehes K, Hook EB. 1991. Inherited ring chromosomes: an
analysis of published cases. Hum Genet 87:320–324.
Linnankivi T, Tienari P, Somer M, K€ahk€ onen M, L€onnqvist T, Valanne L,
Pihko H. 2006. 18q deletions: clinical, molecular, and brain MRI findings
of 14 individuals. Am J Med Genet Part A 140A:331–339.
Maranda B, Lemieux N, Lemyre E. 2006. Familial deletion 18p syndrome:
case report. BMC Med Genet 7:60.
Petersen MB, Bartsch O, Adelsberger PA, Mikkelsen M, Schwinger E,
Antonarakis SE. 1992. Uniparental isodisomy due to duplication of
chromosome 21 occurring in somatic cells monosomic for chromosome
21. Genomics 13:269–274.
Roessler E, Muenke M. 2010. The molecular genetics of holoprosencephaly.
Am J Med Genet Part C 154C:52–61.
Solomon BD, Pineda-Alvarez DE, Mercier S, Raam MS, Odent S, Muenke
M. 2010. Holoprosencephaly flashcards: A summary for the clinician. Am
J Med Genet Part C 154C:3–7.
Tsukahara M, Imaizumi K, Fujita K, Tateishi H, Uchida M. 2001. Familial
Del(18p) syndrome. Am J Med Genet 99:67–69.
Turleau C. 2008. Monosomy 18p. Orphanet J Rare Dis 3:4.
Velagaleti GV, Harris S, Carpenter NJ, Coldwell J, Say B. 1996. Familial
deletion of chromosome 18 (p11.2). Ann Genet 39:201–204.