Tetrasomy 18p: Report of the Molecular and
Clinical Findings of 43 Individuals
Courtney Sebold,1Elizabeth Roeder,1Marsha Zimmerman,1Bridgette Soileau,1Patricia Heard,1
Erika Carter,1Martha Schatz,2W. Abraham White,2Brian Perry,3Kent Reinker,4Louise O’Donnell,1,5
Jack Lancaster,6John Li,6Minire Hasi,1Annice Hill,1Lauren Pankratz,1Daniel E. Hale,1
and Jannine D. Cody1,7*
1Department of Pediatrics, University of Texas Health Science Center at San Antonio, San Antonio, Texas
2Department of Ophthalmology, University of Texas Health Science Center at San Antonio, San Antonio, Texas
3Ear Medical Group, San Antonio, Texas, San Antonio, Texas
4Department of Orthopedics, University of Texas Health Science Center at San Antonio, San Antonio, Texas
5Department of Psychiatry, University of Texas Health Science Center at San Antonio, San Antonio, Texas
6Research Imaging Institute, University of Texas Health Science Center at San Antonio, San Antonio, Texas
7Chromosome 18 Registry and Research Society, San Antonio, Texas
Received 24 December 2009; Accepted 16 June 2010
Thus far, the phenotype of tetrasomy 18p has been primarily
delineated by published case series and reports. Findings re-
portedinmorethan 25%ofthese cases includeneonatalfeeding
problems, growth retardation, microcephaly, strabismus,
muscle tone abnormalities, scoliosis/kyphosis, and variants on
brain MRI. Developmentaldelays and cognitive impairment are
universally present. The purpose of this study was to more fully
with tetrasomy 18p diagnosed via routine karyotype. The
medical records of 42 of these 43 individuals were reviewed. In
order to gain additional phenotypic data, 31 individuals with
tetrasomy 18p underwent a series of clinical evaluations at the
Chromosome 18 Clinical Research Center. Results from the
molecular analysis indicated that 42 of 43 samples analyzed had
also trisomic for a section of proximal 18q. The results of the
medical records review and clinical evaluations expand the
phenotypic description of tetrasomy 18p to include neonatal
loss; seizures; refractive errors; constipation and gastroesopha-
geal reflux; cryptorchidism; heart defects; and foot anomalies.
Additional findings identified in a small number of individuals
include hernias, myelomeningocele, kidney defects, short stat-
ure, and failure to respond to growth hormone stimulation
testing. Additionally, a profile of dysmorphic features is
for individuals with tetrasomy 18p is suggested.
? 2010 Wiley-Liss, Inc.
Key words: tetrasomy 18p; isochromosome 18p
Isochromosome 18p appears to be one of the most commonly
observed isochromosomes [Kotzot et al., 1996]. The phenotype of
tetrasomy 18p has been delineated through multiple case reports
and case series. A thorough review of the literature revealed an
average birth weight of 2,519g, which falls between the 3rd and
Grant sponsor: The Chromosome 18 Registry & Research Society; Grant
sponsor: Institute for the Integration of Medicine and Science (National
Center for Research Resources); Grant number: UL 1RR025767; Grant
sponsor: CHRISTUS Santa Rosa Children’s Hospital.
Jannine D. Cody, Department of Pediatrics, UT Health Science Center,
Published online 18 August 2010 in Wiley Online Library
How to Cite this Article:
Sebold C, Roeder E, Zimmerman M, Soileau
B, Heard P, Carter E, Schatz M, White WA,
Perry B, Reinker K, O’Donnell L, Lancaster J,
JD. 2010. Tetrasomy 18p: Report of the
molecular and clinical findings of 43
Am J Med Genet Part A 152A:2164–2172.
? 2010 Wiley-Liss, Inc.
10th centile. The average birth length is 50.1cm, which is at
approximately the 50th centile. The findings described in these
65 case reports and series are presented in Table I. The most
common findings included neonatal feeding problems, growth
retardation, microcephaly, strabismus, abnormalities in muscle
tone, scoliosis/kyphosis, and variants on MRI of the brain. Dys-
nose; a high-arched palate; a small mouth; and either prognathism
or micrognathia [Swingle et al., 2006].
The molecular mechanism of isochromosome 18p formation
has been discussed in several publications [Bugge et al., 1996;
arises as a result of two independent events: nondisjunction and
centromeric misdivision. The alternative mechanism of formation
of an isochromosome is a U-shaped exchange, which would
typically produce a dicentric isochromosome [Kotzot et al.,
1996]. Hence, it is suspected that nondisjunction and misdivision
are primarily responsible for the formation of isochromosome
18p. The parental origin of the isochromsome has been reported
in five different papers and was found to be maternal in 21 of the
22 cases in which origin could be determined [Bugge et al.,
1996; Eggermann et al., 1996, 1997, 1999; Kotzot et al., 1996].
It appears that, in the majority of cases, nondisjunction occurs
during maternal meiosis II followed by centromeric misdivision,
et al., 1999].
The goal of this paper is to more fully describe the molecular
features and clinical presentation of tetrasomy 18p. A series of
clinical evaluations recommended for individuals with tetrasomy
18p is also presented.
for this study included a diagnosis of tetrasomy 18p confirmed by
a routine karyotype. All components of this study have been
approved by the Institutional Review Board of the University of
Texas Health Science Center at San Antonio (UTHSCSA). All
families were and continue to be involved in the informed consent
process, which is appropriately documented.
Blood samples were collected from all study participants as well as
the biological parents, if available. As routine karyotypes had been
completed prior to the participants’ enrollment in the study, they
forcopy numberchanges byoligonucleotide microarraycompara-
tive genomic hybridization as previously described in Heard et al.
. Custom arrays were designed using the Agilent e-array
software (hg18) and were constructed with 32,000 features
(60-mers) across chromosome 18 and 12,000 features across the
remainder of the genome.
The diagnosisoftetrasomy18p wasconfirmed inall individuals by
obtaining copies of the original karyotype. Medical records were
then obtained from all participants. All available records were
reviewed in detail. Following the record review, the families
were contacted by one of three investigators (ER, CS, MZ) to
confirm the medical history and to provide information that was
the parents’ report. In the few instances where the information
used in data analysis to minimize recall bias. For example, several
parents reported birth weights that were slightly different from the
weight listed in the newborn records. In these cases, we used the
birth and thus not subject to recall bias.
Thegatheringof phenotypic data included evaluations bymultiple
specialties, including neurotology, audiology, ophthalmology, ge-
netics, neurology, orthopedics, and endocrinology. Each specialty
used the standard evaluation that is used in a typical new patient
visit in clinic. Thus, none of the evaluations are considered experi-
mental in nature. The endocrine evaluation also includedbone age
studies, IGF1 and IGFBP3 levels, growth hormone provocative
testing using arginine and clonidine, total T4 and TSH measure-
ments, and FSH, LH, estradiol and testosterone levels in post-
pubertal individuals. Participants also had brain MRIs and skeletal
surveys. Hearing was assessed using sound booth audiometry and/
or an Auditory Brainstem Evoked Response (ABR).
We received blood samples from 43 individuals with tetrasomy
18p diagnosed via routine karyotype. In all but one individual,
aCGH confirmed the diagnosis of tetrasomy 18p molecularly. In
extending from the centromere to 18,536,308 (18q11.2). In order
was removed from the phenotypic analysis. The other 42 indi-
viduals’ region of recombination is located between nucleotides
without sequence data.
The medical charts of 42 individuals with tetrasomy 18p were
reviewed in detail. The medical records from one family were
was gathered via an e-mail interview conducted in English, as the
family was bilingual. All families were interviewed by one of the
investigators.Forty-one individuals hadanisochromosome 18pin
SEBOLD ET AL.
TABLE I. Tetrasomy 18p Findings
Developmental delay/mental retardation
Submucous cleft palate
Recurrent otitis media
Small/narrow ear canals
Abnormal muscle tone
Brain MRI variants
History of constipation
History of gastroesophageal reflux
Other foot anomalies
Growth hormone deficiency
Additional findings identified in single individuals
Giant cell hepatitis
Celiac sprue disease
Abeliovich et al. , Back et al. , Bakshi et al. , Balicek et al. , Balkan et al. , Batista et al. , Blennow and Nielson , Blennow et al. ,
Boyle et al. , Bugge et al. , Callen et al. , Cote et al. , Condron et al. , DeBerardinis et al. , Eggermann et al. , Esmer et al. ,
Fryns et al. [1985, 1990], Kleckzkowska et al. , Kotzot et al. , Mewar et al. , Nielsen et al. , Ogata et al. , Park et al. , Ramegowda et al. ,
Rauch et al. , Rivera et al. , Rocchi et al. , Singer et al. , Swingle et al. , Takeda et al. , Tangheroni et al. , Taylor et al. .
aThese data were not an item scored in the chart review.
bThese data were not collected during the clinical assessment process.
cAn additional seven patients had a history of febrile seizures.
2166 AMERICAN JOURNAL OF MEDICAL GENETICS PART A
individual, lymphocyte analysis revealed 19% of cells with the
isochromosome; fibroblast analysis revealed 68% and 94%
mosaicism in abdominal skin and foreskin, respectively.
paternal age was 34.1 years. The average birth weight was 2,842g
(6.36lbs), and the average birth length was 48.7 centimeters
The large majority of individuals with tetrasomy 18p had some
the neonatal period was feeding difficulty, identified in 83% of
newborns. The feeding problems were frequently related to hypo-
tonia, a high-arched palate, or gastroesophageal reflux. Jaundice
requiring phototherapy was also present in 57% of individuals.
Respiratory distress, though less common than feeding difficulties
and jaundice, was another frequent occurrence in this population
and was seen in 31% of our study participants.
Cardiac. A heart defect was the most common congenital
anomaly present in this population. Of the 32 individuals that had
undergone echocardiograms, 15 had some type of anomaly. The
most common findings were patent ductus arteriosus (7); patent
foramen ovale (3); ventricular septal defect (5); and atrial septal
defect (2). In all but one of these cases, the anomaly closed
spontaneously and did not require surgery. Other cardiac findings
included mild mitral valve regurgitation; mitral valve prolapse;
bicuspid pulmonary valve; hypoplastic transverse aortic arch;
tricuspid valve regurgitation; right ventricular hypertrophy; and
two individuals with pulmonic stenosis. One individual had
‘‘unusual systolic flow.’’
Abdominal. Genitourinary anomalies were also seen within
our population. Of the 19 males, 12 were diagnosed with cryptor-
31 patients who had undergone abdominal ultrasounds, 2 had
horseshoe kidneys and 1 had bladder diverticuli requiring
surgical correction. The only structural anomaly noted in the
gastrointestinal tract was pyloric stenosis, which was identified in
two individuals. Hernias were diagnosed in five individuals. Four
had inguinal hernias while one had an umbilical hernia.
Orthopedic. Six (14%) had clubfoot; two (5%) had vertical
talus; two (5%) had metatarsus adductus; and two (5%) had
rockerbottom feet. Seven (17%) had congenital hip dysplasia.
Centralnervoussystem. Three ofthe42studyparticipantshad
Twenty-four of the 42 participants (57%) had recurrent otitis
media and required the placement of PE tubes.
Chronic constipation was a frequent finding and affected 81% of
our population. Gastrointestinal reflux was another frequent
occurrence and affected 36%.
Muscle tone abnormalities were the most common neurologic
anomaly noted. Forty-one of 42 patients had an abnormality
of muscle tone. Twenty-one had hypotonia; 8 had hypertonia;
and 12 had mixed muscle tone. Approximately one in four had
a seizure disorder. An additional seven individuals had febrile
All study participants had developmental delays as well as some
were within the mild to moderate range of mental retardation.
Table II presents the age range at which key gross motor and
the study population compared with typically developing peers.
Data regardingdegree of cognitive impairmentandotherdevelop-
mental parameters will be presented in a separate publication (in
TABLE II. Age of Attainment of Developmental Milestones
Rolls from side to back N¼31
Sat independently N¼34
Walked alone N¼33
Single words N¼28
2–3 word phrases N¼19
aThe age of acquisition listed for typically developing children indicates the age at which approximately 50% of the Bayley Scales of Infant Development-Second Edition [Bayley, 1993]
normative sample of infants and children demonstrated the skill.
Study children average age of acquisition (months)
Age of acquisition for typically
SEBOLD ET AL.
Of note, within the UTHSCSA population, one female study
participant died suddenly at 13 years of age. She presented to
the ER with a 1-day history of nausea, vomiting, and lethargy,
culminating in asystolic cardiac arrest. Resuscitation efforts were
initiated, but the patient developed multiorgan failure and passed
away. On autopsy, it was revealed that the patient had a massively
distended colon with a large fecal mass measuring 22 cm in
all instances, both parents had normal results. In four of the
remaining 12 families, only the mother had had chromosome
analysis, the results of which were normal. Two were adopted;
thus, birth parents were not available for chromosome analysis. In
the remaining six families, neither parent had undergone chromo-
Clinical Evaluations. All participants were invited to San An-
tonio to receive a series of clinical evaluations. Thirty-one were
evaluated at the Chromosome 18 Clinical Research Center at the
University of Texas Health Science Center at San Antonio. This
sample included 14 males and 17 females. The average age at
evaluation was 9 years 8 months.
All 31 individuals were evaluated by a neurotologist. Although
10 had small ear canals, no other structural anomalies were noted.
Height, weight, and head circumference were obtained on all
participants. In general, individuals with tetrasomy 18p were short
the 3rd centile for weight (three of whom were also below the 3rd
centile for height). Thirteen (42%) were at or below the 3rd centile
for head circumference.
Nineteen individuals were evaluated by an orthopedist. Kyphosis
was diagnosed in three participants, and scoliosis was identified in
deformity and pes cavus. Two had contractures of the fingers;
two had femoral anteversion; one had a slight Erlenmeyer flask
deformity; and 1 had a contraction of the left elbow, possibly
indicating a hemiparesis.
Twenty-eight underwent behavioral audiometry. Fourteen had
ABR evaluations as well. Hearing loss was identified in nine
individuals. Two had sensorineural hearing loss; three had con-
ductive hearing loss; three had mixed hearing loss. One had an
loss, two had moderate hearing loss, and the remaining two
individuals had a mild or moderate hearing loss in the left ear and
a severe hearing loss in the right ear.
Twenty-four underwent ophthalmologic evaluation. Eighteen
subjects showed evidence of strabismus, with 16 subjects demon-
strating esotropia (7 accommodative, 5 infantile, 2 acquired non-
accommodative, 2 intermittent) 1 subject displaying an esophoria,
and 1 subject diagnosed with intermittent exotropia. Seventeen
subjects were noted to have some type of refractive error. Four had
myopia; eight had hyperopia; and six had astigmatism. Four were
diagnosed with anisometropia.
Thirty-one participants underwent the endocrine clinical evalua-
tion. Six participants (19%) failed both growth hormone provoca-
tive tests (peak growth hormone value <10ng/mL for children,
<5ng/mL for adults) using arginine and clonidine. Height per-
centiles of those who failed growth hormone stimulation testing
ranged from the 9th–70th percentile. Two of the six individuals
were children who fulfilled more traditional growth hormone
deficiency criteria with height in the lowest quartile for age and
had low IGF-1 levels. It was recommended that these children seek
with height at the 10th percentile and low IGF-1 levels. Given the
controversy surrounding treatment of adult growth hormone
deficiency, it was recommended that this family discuss growth
three individuals who failed both growth hormone provocative
had been drifiting down from the 50th to the 10th percentile over
the past several years. For these individuals, close monitoring of
evaluations were normal.
Twenty-four families consented to have a sedated brain MRI.
However, only 8 of the 24 responded to the sedative used in our
protocol: chloral hydrate. Four additional individuals had MRIs
without sedation. Among the 12 patients that were scanned, three
had enlargement of the lateral ventricles, and three had a thin or
small corpus callosum. Two had minor signal abnormalities. One
individual had a lipoma of the ambient cistern. Some individuals
had more than one abnormality noted on brain MRI.
All 31 participants were evaluated by a board-certified clinical
geneticist (ER). Features noted in more than 25% of individuals
are listed in Table III.
2168 AMERICAN JOURNAL OF MEDICAL GENETICS PART A
Photographs of individuals exhibiting the typical facial features
of tetrasomy 18p are included in Figure 1.
In this report, we present the largest series of individuals with
growth retardation, microcephaly, strabismus, abnormalities
in muscle tone, scoliosis/kyphosis, and variants on brain MRI.
Developmental delays and cognitive impairment are also univer-
sally present. A thorough chart review of 42 patients and clinical
evaluations of 31 of these patients allows us to expand the pheno-
typic spectrum of tetrasomy 18p to include neonatal jaundice,
recurrent otitis media, hearing loss, seizures, refractive errors, a
history of constipation and gastroesophageal reflux, heart defects,
and pes planus. Less frequently, kidney defects, hernias, and
myelomeningocele as well as short stature and failure to respond
with tetrasomy 18p. Some individuals who did not respond to
growth hormone stimulation testing and who also had low IGF-1
values still had normal growth for unknown reasons. Based on our
data as well as the reports in the literature, guidelines for the
evaluation of individuals with tetrasomy 18p are suggested in
Of interest, one of the UTHSCSA cases had mosaicism. Reports
several reports of a prenatal diagnosis of mosaic tetrasomy 18p
followed by termination of the pregnancy [Gocke et al., 1986;
Verschraegen-Spae et al., 1993; Blennow et al., 1995; Pinto et al.,
1998]. Thus, these reports do not provide useful information
18p. Pfeiffer and Schulze  reported three cases of presumed
mosaic tetrasomy 18p. These individuals had features similar to
those reported in individuals with full tetrasomy 18p. Similarly,
the UTHSCSA patient with mosaicism also had features of the
tetrasomy 18p phenotype, including neonatal feeding problems;
cryptorchidism; vision problems; recurrent otitis media; and mild
diagnosed with pneumonia and adenoid hypertrophy.
The high de novo rate of isochromosome 18p in our patients is
consistent with the literature. In fact, only a handful of reports of
inherited cases exist. Takeda et al.  and Taylor et al. 
both reported families in which the mother had a karyotype
of 47,XX,del(18p),þi(18p). The mother reported by Takeda
was phenotypically normal and had two pregnancies affected by
Taylor et al.  had one daughter with tetrasomy 18p and one
daughter with 18p-syndrome. This mother was reportedly pheno-
typically normal, though small. Abeliovich et al.  reported a
(3%) for tetrasomy 18p. This individual was slightly dysmorphic,
though her medical and developmental histories were normal.
Boyle et al.  reported a family in which two maternal-half
sisters had tetrasomy 18p. Karyotype and molecular analysis of the
isochromosome 18. Though it appears that tetrasomy 18p is a de
novo occurrence in the great majority of cases, these case reports
show that, in some families, the abnormality is familial. This has
significant implications for genetic counseling for these families
and should be taken into account when providing information
regarding recurrence risks.
Some authors have suggested that advanced maternal age may
play a role in isochromosome 18p formation [Bugge et al., 1996;
frequent mechanism of isochromosome formation involves non-
disjunction in maternal meiosis II. In this sample, the average
findings were consistent with the literature, and given that there is
no evidence for any imprinting effects by genes on 18, we did not
perform parental origin studies. We felt that such studies were
unlikely to provide new information.
There are some limitations to this study. There may have been
some degree of ascertainment bias for those studies that were not
echocardiograms and renal ultrasounds. Forexample,itis possible
that only individuals with a heart murmur were referred for an
echocardiogram, or that renal ultrasounds were performed on
individual with recurrent urinary tract infections. Thus, there may
be some minor heart or kidney defects that have gone undetected.
Despite this limitation, this study serves as a critical step in the
delineation of the natural history of tetrasomy 18p. This study
TABLE III. Features Noted During Genetics Evaluation
Ptosis or hooded eyes
Posteriorly rotated ears
Small ears (at or below 3rd centile)
Abnormal columella (broad, or extends
below alae nasi)
Thin upper lip vermilion
Abnormal Cupid’s bow (smooth, ill-defined, narrow)
Palatal abnormalities (high, arched, narrow)
Prominent and/or pointed chin
Mild/partial syndactyly of the toes
Prominent finger tip pads
Gap between 1st and 2nd toes
Proximally placed anus
aThis part of the exam was deferred in some patients.
SEBOLD ET AL.
FIG. 1. Photographsofindividualswithtetrasomy18patvaryingages.A:1year8months,(B)3years10months,(C)6years2months,(D)7years
2 months, (E) 7 years 3 months, (F) 7 years 7 months, (G) 8 years 9 months, (H) 12 years 11 months, (I) 19 years, (J) 20 years 9 months.
2170 AMERICAN JOURNAL OF MEDICAL GENETICS PART A
of affected individuals. Future studies include the analysis of the
results of comprehensive developmental, behavioral, and neuro-
cognitive evaluations conducted with our subject participants
through the Chromosome 18 Research Center.
We would like to thank the families who have so generously
supported this work with their time and enthusiasm. This work
was supported by The Chromosome 18 Registry & Research
Society. This project was also supported in part by the Institute
for the Integration of Medicine and Science (UL 1RR025767;
National Center for Research Resources) and CHRISTUS Santa
Rosa Children’s Hospital.
Abeliovich D, Dagan J, Levy A, Steinberg A, Zlotogora J. 1993. Isochro-
mosome 18p in a mother and her child. Am J Med Genet 46:392–393.
Back E, Toder R, Voiculescu I, Wildberg A, Schempp W. 1994. De novo
isochromosome 18p in two patients: Cytogenetic diagnosis and confir-
mation by chromosome painting. Clin Genet 45:301–304.
Bakshi SR, Brahmbhatt MM, Trivedi PJ, Chudoba I. 2006. Constitutional
tetrasomy 18p. Indian Pediatr 43:357–359.
no. 18 chromosome in a mentally retarded girl. Clin Genet 9:192–196.
Balkan M, Duran H, Budak T. 2009. Tetrasomy 18p in a male dysmorphic
child in southeast Turkey. J Genet 88:337–340.
Tentative delineation of a syndrome. J Med Genet 20:144–147.
Bayley N. 1993. The Bayley Scales of Infant Development, Second Edition.
San Antonio, TX: The Psychological Corporation.
Blennow E, Nielson KB. 1991. Molecular identification of a small super-
numerary markerchromosome by in situ hybridization: Diagnosis of an
isochromosome 18p with probe L1.84. Clin Genet 39:429–433.
E, Gillberg C, Nordenskjold M. 1995. Fifty probands with extra struc-
turally abnormal chromosomes characterized by fluorescence in situ
hybridization. Am J Med Genet 55:85–94.
Boyle J, Sangha K, Dill F, Robinson WP, Yong SL. 2001. Grandmaternal
J Med Genet 101:65–69.
Bugge M, Blennow E, Friedrich U, Petersen MB, Pedeutour F, Tsezou A,
f ? rum A, Hermann S, Lyngbye T, Sarri C, Avramopoulos D, Kitsiou S,
Lambert JC, Guzda M, Tommerup N, Brf ? ndum-Nielsen K. 1996.
Tetrasomy 18p de novo: Parental origin and different mechanisms of
formation. Eur J Hum Genet 3:160–167.
Callen DF, Freemantle CJ, Ringenbergs ML, Baker E, Eyre HJ, Romain D,
Hann EA. 1990. The isochromosome 18p syndrome: Confirmation of
cytogenetic diagnosis in nine cases by in situ hybridization. Am J Hum
Condron CJ, Cantwell R, Kaufman RL, Brown SB, Warren RJ. 1974. The
supernumerary isochromosome 18 syndrome (þ18pi). Birth Defects
Orig Artic Ser 10:36–42.
Cote GB, Petmezaki S, Bastakis N. 1979. A gene for hypospadias in a child
with presumed tetrasomy18p. Am J Med Genet 4:141–146.
DeBerardinis RJ, Medne L, Spinner NB, Zackai EH. 2005. DiGeorge
Am J Med Genet Part A 138A:155–159.
Eggermann T, Engels H, Moskalonek B, N€ othen MM, M€ uller-Navia J,
Schleiermacher E, Schwanitz G, Stengel-Rutkowski S. 1996. Tetrasomy
18p de novo: Identification by FISH with conventional and microdis-
section probes and analysis of parental origin and formation by short
sequence repeat typing. Hum Genet 97:568–572.
Eggermann T, Engels H, Apacik C, Moskalonek B, M€ uller-Navia J,
Schwanitz G, Stengel-Rutkowski S. 1997. Tetrasomy 18p caused by
paternal meiotic nondisjuntion. Eur J Hum Genet 5:175–177.
Eggermann T, Schubert R, Engels H, Apacik C, Stengel-Rutkowski S,
Haefliger C, Emiliani V, Ricagni C, Schwanitz G. 1999. Formation of
supernumerary euchromatic short arm isochromosomes: Parent and
cell stage of origin in new cases and review of the literature. Ann Genet
Esmer CM, Frias S, G? omez L, Carnevale A. 1994. Tetrasomy 18p in two
cases. Confirmation by in situ hybridization. Ann G? en? et 37:156–159.
Fryns JP, Kleczkowska A, Marien P, Van Den Berghe H. 1985. 18p
Tetrasomy. Further evidence for a distinctive clinical syndrome. Ann
G? en? et 28:111–112.
Fryns JP, Grubben C, Van Den Berghe H. 1990. Penile enlargement in
tetrasomy 18p: An additional feature? Ann G? en? et 33:239–240.
Gocke H, Muradow I, Zerres K, Hansmann H. 1986. Mosaicism of
fetus at 21 weeks. Prenat Diagn 6:151–157.
Heard PL, Carter EM, Crandall AC, Sebold C, Hale De, Cody JD. 2009.
High resolution genomic analysis of 18q- using oligo-microarray
comparative genomic hybridization. Am J Med Genet Part A 149A:
Berghe H. 1986. Trisomy (18q) and tetrasomy (18p) resulting from
isochromosome formation. Clin Genet 30:503–508.
Kotzot D, Bundscherer G, Bernasconi F, Brecevic L, Lurie IW, Basaran S,
Baccicchetti C, H€ oller A, Castellan C, Braun-Quentin C, Pfeiffer RA,
Schinzel A. 1996. Isochromosome 18p results from maternal meiosis II
nondisjunction. Eur J Hum Genet 4:168–174.
Mewar R, Harrison W, Overhauser J. 1993. Confirmation of isochromo-
some 18p using whole chromosome arm-specific fluorescence in situ
hybridization. Cytogen Cell Genet 64:1–4.
Nielsen K, Dyggve H, Friedrich U, Hobolth N, Lyngbye T, Mikkelsen M.
1978. Small metacentric nonsatellited extra chromosome: Report of five
FIG. 2. Suggested Evaluations for Individuals with Tetrasomy 18p.
SEBOLD ET AL.
mentally retarded individuals and review of literature. Contribution to Download full-text
Further Delineation of a New Syndrome. Hum Genet 44:59–69.
presumptive þi(18p) associated with serum IgA deficiency. Clin Genet
Park VM, Gustashaw KM, Bilenker RM, Golden WL. 1991. Diagnosis of
tetrasomy 18p using in situ hybridization of a DNA probe to metaphase
chromosomes. Am J Med Genet 41:180–183.
Pfeiffer RA, Schulze T. 1994. Mosaicism in three cases of 47,XY(or XX),
þi(18)(p10) detected by interphase FISH of buccal mucosa. Ann G? en? et
Pinto MR, Silva MLF, Ribeiro MC, Pina R. 1998. Prenatal diagnosis of
mosaicism for tetrasomy 18p: Cytogenetic, FISH, and morphological
findings. Prenat Diagn 18:1095–1097.
Ramegowda S, Gawde HM, Hyderi A, Savitha MR, Patel ZM, Krishna-
murthy B, Ramachandra NB. 2006. De novo isochromosome 18p in a
female dysmorphic child. J Appl Genet 47:397–401.
Rauch A, Pfeiffer RA, Trautmann U, Liehr T, Rott HD, Ulmer R. 1992. A
study of ten small supernumerary (marker) chromosomes identified by
flouorescence in situ hybridization (FISH). Clin Genet 42:84–90.
RiveraH,M€ oller HernandezA, Enr? ıque-GuerraMA, Arreola R,Cant? uJM.
1984. Tetrasomy 18p: A distinctive syndrome. Ann G? en? et 27:187–189.
Rocchi M, Stormi M, Archidiacono N, Filippi G. 1979. Extra small
metacentric chromosome identified as i(18p). J Med Genet 16:69–73.
phenotype. Am J Med Genet 36:144–147.
Swingle HM, Ringdahl J, Mraz R, Patil S, Keppler-Noreuil K. 2006.
Behavioral management of a long-term survivor with tetrasomy 18p.
Am J Med Genet Part A 140A:276–280.
mother with trisomy 18p. J Med Genet 26:195–197.
Tangheroni w, Cao A, Furbetta M. 1973. Multiple anomalies associated
with an extra small metacentric chromosome: Modified Giemsa stain
results. Humangenetik 18:291–295.
Taylor KM, Wolfinger HL, Brown MG, Chadwick DL. 1975. Origin of a
small metacentric chromosome: Familial and cytogenetic evidence. Clin
cytogenetic characterization of marker chromosomes found at prenatal
diagnosis. Prenat Diagn 13:385–394.
2172 AMERICAN JOURNAL OF MEDICAL GENETICS PART A