American Journal of Medical Genetics 80:454–458 (1998)
Syndrome of Facial, Oral, and Digital Anomalies
Due to 7q21.2→q22.1 Duplication
T. Lukusa and J.-P. Fryns*
Center for Human Genetics, University Hospital of Leuven, Leuven, Belgium
We report on an 18-year-old man with mod-
erate mental retardation, multiple congeni-
tal anomalies and partial trisomy
7q21.2→q22.1, as the unbalanced product of
a familial balanced 7q/6q insertion translo-
cation. To the best of our knowledge, this is
the first example of interstitial trisomy
7q21.2→q22.1 reported. The syndrome is
characterized by the presence of facial, oral,
and digital anomalies: 1) macrocephaly with
frontal bossing, hypertelorism, small palpe-
bral fissures with downward slant; 2) lobu-
lated tongue, multiple intrabuccal frenula,
oligodontia and enamel hypoplasia; 3) cuta-
neous syndactyly of fingers II-III and III-IV,
broad and short fingertips with fetal pads,
broad thumbs, and halluces. Am. J. Med.
Genet. 80:454–458, 1998. © 1998 Wiley-Liss, Inc.
KEY WORDS: trisomy 7q; insertional trans-
location; oro-facial and digi-
tal anomalies; chromosome 7;
chromosome 6
INTRODUCTION
Since the use of banding techniques was introduced
in human cytogenetics, at least 41 liveborn patients
with well documented partial 7q trisomy have been
published: 36 cases previously reviewed by Novales et
al. [1982], Johnson et al. [1986], and Forabosco et al.
[1988], and five additional cases: one of the two cases
published by Zackowsky et al. [1990], three cases re-
ported by Romain et al. [1990], and one case by Hum-
phreys et al. [1991]. In most of them, a terminal partial
trisomy was present involving a variety of segments
from 7q21→qter to 7q35→qter, whereas in only seven
cases, an interstitial partial trisomy involving the seg-
ments 7q11.2→q11.23 [Hoo et al., 1982], 7q11→q22
[Kardon et al., 1983], 7q21.12→q31.32 [Humphreys et
al., 1991], or 7q22→q31 [Grace et al., 1973; Berger et
*Correspondence to: Jean-Pierre Fryns, Center for Human Ge-
netics, Herestraat 49, B-3000 Leuven, Belgium.
Received 23 January 1998; Accepted 26 May 1998
© 1998 Wiley-Liss, Inc.
al., 1974; Serville et al., 1975; Romain et al., 1990] was
described.
The present report concerns a mentally retarded
adult male with partial 7q21.2→q22.1 trisomy.
CLINICAL REPORT
The index patient of this report, B.C., is an 18-year-
old moderately mentally retarded man referred for di-
agnostic evaluation. He was the fourth and youngest
child born to healthy non-consanguineous parents. His
only sister was born prematurely and died shortly after
birth. No further data are available on this child. His
two older brothers, now 22 and 20 years old, are nor-
mal. At his birth the mother was 28 years and the
father (deceased from a lung carcinoma at the age of 40
years) 32 years old. He was born at term after an un-
eventful pregnancy. Birthweight was 2,650 g. In the
neonatal period generalized hypotonia with poor suck,
marked retrognathia, and a very weak cry were noted.
Feeding difficulties and recurrent infections were pre-
sent during infancy, and his weight gain was slow. At
the age of 1 year, delay in psychomotor development
was noted: he could not sit without support and could
hardly roll from supine to prone position. He started to
walk without support at 2 years. At the age of 6 years
he was integrated in a special school for the moderately
mentally retarded (IQt 34 - WISC-R). Now, at the age
of 18 years, verbal skills are relatively better than per-
formance skills, but social integration is difficult with
episodes of aggressive behaviour especially towards
children.
Clinical examinations at different ages during in-
fancy (Fig. 1) showed relative macrocephaly with fron-
tal bossing, hypertelorism, small palpebral fissures
with downward slant, left divergent strabismus, and
apparently low set, normal ears. Oral anomalies were
remarkable: short upper lip, retrognathia, high arched
palate, lobulated tongue with absence of frenulum lin-
guae, presence of multiple intrabuccal frenula linking
inferior and superior labia to the alveolar processes,
oligodontia, and enamel hypoplasia. The neck was
short. There was cutaneous syndactyly of fingers II-III
and III-IV; fingertips were broad and short with fetal
pads, and thumbs and halluces were noted to be broad.
CT scan of the brain at the age of 1 year showed
discrete bifrontal cortical atrophy with subdural hy-
groma, but these findings were not confirmed on a con-
 Syndrome Due to 7q21.2→q22.1 Duplication 455

Fig. 1. The patient’s appearance at different ages during childhood. A: Note frontal bossing, downward slant of palpebral fissures, short upper lip,
retrognathia, cutaneous syndactyly. B: Note macrocephaly, hypertelorism, ‘‘tent-like mouth,’’ absence of frenulum linguae. C: Note small eyes, lobulated
tongue. D: Note long fingers.
456 Lukusa and Fryns
trol CT scan at the age of 8 years. Ophthalmologic ex-
amination showed left divergent strabismus and atypi-
cal, irregular pigmentation of both fundi. Now at the
age of 18 years, weight is 46.6 kg (third centile is 50
kg), height 155.5 cm (third centile is 161 cm) and OFC
57 cm (75th centile). Craniofacial anomalies and intra-
oral anomalies are identical as described at younger
age. There is general hypotonia with joint hypermobil-
ity, especially of wrists and distal interphalangeal
joints. Secondary sexual development is normal. Ex-
cept for lumbar platyspondyly and diastasis of the pu-
bic bones, no additional anomalies were noted on a
skeletal survey.
CHROMOSOMAL STUDIES
Metaphase chromosomes were prepared from phyto-
hemagglutinin-stimulated peripheral lymphocytes and
G- and T-banded using standard techniques.
Analysis of the patient’s chromosomes showed a
male karyotype with additional material inserted
within the long arm of one of the chromosomes 6 giving
an abnormally long derivative chromosome 6 [6q+],
and no other evidence of deletion or duplication else-
where (Fig. 2a).
The mother had a normal 46,XX female karyotype.
Both normal brothers were carriers of a balanced in-
sertional 7q/6q translocation (Fig. 2b), the segment
7q21.2→q22.1 lacking on one chromosome 7 [7q-] and
inserted into the long arm of one chromosomes 6 [6q+]
at the 6q16.2 band (Fig. 3).
Whole chromosome painting with a probe for chro-
mosome 7 following the methodology of the manu-
facturer (CAMBIO, Cambridge, UK) confirmed the cy-
togenetic findings by showing presence of material
from chromosome 7 on the long arm of chromosome 6
(Fig. 4).
Thus, the brothers’ karyotype was 46,XY,ins(6;7)
(q16.2)(q21.2→22.1) and the additional material on
the proband’s chromosome 6q was identified as
7q21.2→q22.1 and the karyotype was 46,XY der(6)
ins(6;7)(q16.2;q212→q221).
DISCUSSION
To the best of our knowledge, this patient is the first
case of trisomy for the interstitial 7q21.2→7q22.1 re-
Fig. 2. A: The patient’s partial karyotype (T-banding). Arrow indicates the derivative chromosome 6. Both chromosomes 7 are normal. B: Partial
karyotype of one of the brothers (T-banding) with the balanced translocation. Arrows show the derivative chromosomes 6 and 7.
gion ever reported. The partial 7q21.2→q22.1 duplica-
tion is the unbalanced product of a familial insertional
7q/6q translocation. Felding and Mitelman [1979] re-
ported a newborn boy with partial trisomy 7q32→qter
equally resulting from an insertional 7q/6q transloca-
tion as part of a complex balanced translocation
t(6;7;20) in the mother and concomitant partial trisomy
for the segment 20p11→pter. No other case has been
published with partial 7q trisomy resulting from trans-
location 7q/6q. Among the seven patients hitherto re-
ported with interstitial trisomy 7q, four cases [Grace et
al., 1973; Serville et al., 1975; Berger et al., 1974; Hum-
phreys et al., 1991] resulted from familial insertion
translocation, whereas three cases were de novo [Hoo
et al., 1982; Kardon et al., 1983; Romain et al., 1990]
and were assumed to be related to unequal crossing-
over in the mother.
Partial trisomy of the long arm of chromosome 7 in-
variably results in a MCA/MR syndrome. Up to now,
attempts have been made to delineate at least three
different partial trisomy 7q syndromes resulting from
7q32→qter, 7q31→qter, and interstitial 7q22→q31 du-
plications, respectively [Berger et al., 1974; Vogel,
1977; Novales et al., 1982; Couzin et al., 1986;
Forabosco et al., 1988].
Three patients [Grace et al., 1973; Berger et al.,
1974; Serville et al., 1975] with interstitial duplication
7q22→q31 served to delineate the clinical data related
to interstitial trisomy 7q. They had developmental de-
lay, hypotonia, frontal bossing, small palpebral fis-
sures, hypertelorism with epicanthal folds, strabismus
and depressed nasal bridge, low-set ears and, charac-
teristically, no skeletal anomalies, no microretrogna-
thia, no cleft palate, and no early postnatal death.
Our patient is trisomic for the segment
7q21.2→q22.1 which partially overlaps with the seg-
ment 7q22→q31. He is mentally retarded and hypo-
tonic. Almost all the facial anomalies of the interstitial
trisomy 7q22→q31 syndrome are observed with, in ad-
dition, distinct oral and digital anomalies. Oral anoma-
lies consisting of high arched palate, oligodontia with
enamel hypoplasia, and multiple intrabuccal frenula
are very striking findings which have never been re-
corded previously in interstitial 7q trisomy. They prob-
ably contributed to feeding difficulties and subsequent
 Syndrome Due to 7q21.2→q22.1 Duplication 457

Fig. 3. Partial karyotype and idiogram (G-banding) of normal (left) and derivative (right) chromosomes 6 and 7 from one of the brothers. Breakpoints
are indicated on the normal chromosomes by arrows.

Fig. 4. Whole chromosome paint (A: painting; B: G-banding) with chromosome 7 specific library on metaphase from one of the brothers revealing
presence of translocated material from chromosome 7 on the long arm of chromosome 6.
458 Lukusa and Fryns
poor weight gain registered during infancy. Likewise,
digital anomalies consisting of cutaneous syndactyly,
broad and short fingertips with fetal pads, and broad
thumbs and halluces are not known as part of intersti-
tial trisomy syndrome.
Thus, the present case combines facial characteris-
tics of interstitial trisomy 7q syndrome, and oral and
digital anomalies, evoking in some way oral-facial-
digital (OFD) syndrome [Toriello, 1993; Shashi et al.,
1995]. To the best of our knowledge, no similar condi-
tion has been described previously.
REFERENCES
Berger R, Derre J, Ortiz MA (1974): Les trisomies partielles du bras long
du chromosome 7. Nouv Presse Med 3:1801–1804.
Couzin DA, Haites N, Watt JL, Johnston AW (1986): Partial trisomy 7
(q32→qter) syndrome in two children. J Med Genet 23:461–465.
Felding I, Mitelman F (1979): A child with partial trisomy 7 and 20 inher-
ited from the mother. Hereditas 91:91–95.
Forabosco A, Baroncini A, Dalpra L, Chessa L, Giannotti A, Maccagnani F,
Dallapiccola B (1988): The phenotype of partial dup(7q) reconsidered: a
report of five new cases. Clin Genet 34:48–59.
Grace E, Sutherland GR, Stark GD, Bain AD (1973): Partial trisomy of 7q
resulting from a familial translocation. Ann Genet 16:51–54.
Hoo JJ, Lorenz R, Fischer A, Fuhrmann W (1982): Tiny interstitial dupli-
cation of proximal 7q in association with a maternal paracentric inver-
sion. Hum Genet 62:113–116.
Humphreys MW, Magee AC, Nevin NC (1991): Duplication 7q resulting
from a maternal insertional translocation. J Med Genet 28:574.
Johnson DD, Michels VV, Aas MA, Dewald GW (1986): Duplication of
7q31.2→7qter and deficiency of 18qter: report of two patients and lit-
erature review. Am J Med Genet 25:477–488.
Kardon NB, Pollack L, Davis J, Broekman A, Krauss M (1983): De novo
duplication of 7q11→q22 region. J Med Genet 20:471–473.
Novales MA, Fernandez-Novoa C, Hevia A, Martin VS, Galera H (1982):
Partial trisomy for the long arm of chromosome 7. Case report and
review. Hum Genet 62:378–381.
Romain DR, Cairney H, Stewart D, Columbano-Green LM, Garry M,
Parslow MI, Parfitt R, Smynthe RH, Chapman CJ (1990): Three cases
of partial trisomy 7q owing to rare structural rearrangements of chro-
mosome 7. J Med Genet 27:109–113.
Serville F, Broustet A, Sandler B, Bourdeau M-J, Leloup M (1975): Triso-
mie 7q partielle. Ann Genet 18:67–70.
Shashi V, Clark P, Rogol AD, Wilson WG (1995): Absent pituitary gland in
two brothers with an oral-facial-digital syndrome resembling OFDS II
and VI:a new type of OFDS? Am J Med Genet 57:22–26.
Toriello HV (1993): Oral-facial-digital syndromes, 1992. Clin Dysmorphol
2:95–105.
Vogel W (1977): Partial duplication 7q. In Yunis JJ (ed): New chromosomal
syndromes. New York: Academic Press, p 185–195.
Zackowski JL, Raffel LJ, McDaniel LD, Schwartz S (1990): A paternal
balanced translocation [t(7;22)(q32;q13.3)] leading to reciprocal unbal-
anced karyotypes in two consecutive pregnancies. Ann Genet 33:113–
116.