American Journal of Medical Genetics 75:59–61 (1998)
Unique Cardiac and Cerebral Anomalies With
Chondrodysplasia Punctata
David J. Ciske,1 Darrel J. Waggoner,1 and S. Bruce Dowton2*
1
Edward Mallinckrodt Department of Pediatrics, Washington University School of Medicine, St. Louis, Missouri
2
James S. McDonnell Department of Genetics, Washington University School of Medicine, St. Louis, Missouri
Chondrodysplasia punctata (CDP) is associ-
ated with a variety of genetic and nonge-
netic conditions. We report a girl with CDP,
complex congenital cardiac disease, central
nervous system (CNS) anomalies, and clini-
cal findings that resemble those of the sibs
described by Toriello et al. [1993, Am J Med
Genet 47:797–799]. The cardiac defects and
CNS abnormalities reported are unique in
the context of CDP and may serve to expand
the phenotypic spectrum of the unique form
of CDP described by Toriello et al. [1993].
Am. J. Med. Genet. 75:59–61, 1998.
© 1998 Wiley-Liss, Inc.
KEY WORDS: chondrodysplasia punctata;
brachytelephalangy; coarcta-
tion of the aorta; atrioven-
tricular canal; brain anoma-
lies
INTRODUCTION
Chondrodysplasia punctata (CDP) is a radiographic
finding of newborns and infants that is sometimes seen
with a variety of other anomalies. Classification of dis-
orders associated with CDP has focused on defining
inheritance patterns and related clinical characteris-
tics [Bennett et al., 1992; Pryde et al., 1993; Wulfsberg
et al., 1992]. Toriello et al. [1993] described a brother
and sister with CDP and raised the possibility of a
unique syndrome with CDP as a component. Autoso-
mal recessive inheritance was implied in the family by
involvement of male and female sibs. We describe a
child with CDP and clinical findings resembling those
of the sibs described by Toriello et al. [1993] and ex-
pand the phenotype of this condition.
C.A. was born at 42 weeks of gestation to nonconsan-
guineous parents. Pregnancy was complicated by expo-
*Correspondence to: Dr. S. Bruce Dowton, Division of Medical
Genetics, Department of Pediatrics, St. Louis Children’s Hospi-
tal, Washington University School of Medicine, One Children’s
Place, St. Louis, MO 63110.
Received 3 April 1997; Accepted 28 July 1997
© 1998 Wiley-Liss, Inc.
sure to oral contraceptive medication, but no other ex-
posure to teratogens occurred. The infant was deliv-
ered to a 23-year-old gravida 2 para 1 mother by
caesarean section for double footling breech presenta-
tion. Birth weight was 3,850 g (75th centile), length
was 51 cm (50th centile), and occipitofrontal circumfer-
ence was 36.5 cm (75th centile). She also had brachy-
cephaly, bitemporal narrowing, a large anterior fonta-
nelle, and a round face. She had hypertelorism (inner
canthal distance of 2.8 cm, >97th centile), prominent
ocular globes, and asymmetry of the palpebral aperture
in the coronal plane; the top lid was tented and
the lower lid was flat when the eyes were open. The
nasal root was depressed and the bridge was broad
(Fig. 1). The palate was high and intact, and a bifid
uvula was present. Her ears appeared low-set and
asymmetric, with a flat overfolded helix on the left.
There was ulnar deviation of the fingers at the meta-
carpophalangeal joint, bilateral proximal cutaneous
dyndactyly of fingers 3 and 4, and deep plantar and
palmar creases.
Additional evaluations were performed. Echocardi-
ography demonstrated an incomplete atrioventricular
canal, small left ventricle, and coarctation of the aorta.
Ophthalmologic exam showed a right retinal coloboma.
Ultrasonography showed calcifications in the liver,
mild splenomegaly, and bilateral echogenic renal pyra-
mids without hydronephrosis. Cranial ultrasound ex-
amination disclosed partial absence of the corpus cal-
losum, an enlarged cisterna magna, a small vermis,
and an intermediate enlargement of the anterior horns
of the lateral ventricles. Radiographs of the skeleton
showed punctate calcifications at the proximal humer-
al and femoral epiphyses bilaterally (Fig. 2), thin and
gracile ribs, broad and triangular metaphyses, and
brachytelephalangy of the hands and feet bilaterally
(Fig. 3).
The patient’s clinical problems have necessitated
several surgical procedures including repair of the co-
arctation at 6 days and primary repair of the atrioven-
tricular canal at 6 weeks (due to failure to wean from
ventilatory support). She also had a colectomy for nec-
rotizing enterocolitis. At the age of 8 weeks, due to
failure to wean from endotracheal intubation, a trache-
ostomy was performed.
Results of high-resolution chromosome analysis
were normal. Quantification of concentrations of
60 Ciske et al.
Fig. 1. Patient at 10 months of age. A: Frontal view. B: Lateral view.
Note brachycephaly, low-set ears, and overfolded helix.
total plasma very long chain fatty acids, pipecolic
acid, and serum plasmalogens were within reference
ranges.
At age 10 months, her weight was 5.71 kg (<5th cen-
tile) and length was 61 cm (<5th centile). Physical find-
ings were essentially unchanged except for mild con-
tracture of the metacarpophalangeal joint of the third
fingers. Her development has shown steady gain since
discharge home but is delayed for age. She continues to
Fig. 2. Anterioposterior radiograph of the right shoulder. Note epiph-
yseal stippling of proximal humerus.
require tracheostomy and has had several long admis-
sions for viral illnesses.
This child most closely resembles the sibs described
by Toriello et al. [1993], who may represent a poten-
tially separate syndrome associated with CDP. She has
many similarities with these children, including
brachycephaly, ocular colobomata, flat facial profile,
apparently low-set ears, deep palmar creases, and flat
lower eyelids.
In review of all reported cardiac defects in patients
noted to have syndromes with CDP, Fourie [1995] did
not find an association between specific cardiac defects
and disorder type. Cardiac defects included, but were
not limited to, patency of the ductus arteriosus and
foramen ovale, septal defects (ventricular and atrial),
peripheral pulmonary arterial stenosis, tetralogy of
Fallot, and dextrocardia. The cardiac findings observed
in the subject of this report (i.e. coarctation of the aorta
and atrioventricular canal) have not been reported in
other patients with CDP.
Malformations of the central nervous system have
been reported infrequently in nonrhizomelic conditions
associated with CDP but include compression of the
cervical spinal cord [Goodman and Dominguez, 1990],
atlanto-axial instability [Afshani and Girdany, 1972],
and congenital flaccid paraparesis [Curless, 1983]. The
anomalies observed in this patient (partial absence of
the corpus callosum, small size of the vermis, enlarge-
ment of the cisterna magna, and enlargement of the
anterior horns of the lateral ventricles) appear to be
unique in the presence of CDP.
The present report reemphasizes the broad and over-
lapping spectrum of physical manifestations associated
with CDP. In addition, we expand this spectrum fur-
ther with the addition of a unique congenital heart de-
fect and previously unreported structural brain anoma-
lies in a patient who most clearly resembles the sibs
described by Toriello et al. [1993].

Fig. 3. Radiographs demonstrating brachytelephalangy. A: Hand. B: Feet.
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