2008 Barcelona - European Society of Human Genetics

Clinical genetics
curved radii, ulnae, tibiae and fibulae
In autopsy, multiple visceral abnormalities of major organs such as
bilateral polycystic kidney and intestinal malrotations were detected .
Based on radiological criteria and the pattern of associated abnormalities,
short rib-polydactyly syndrome type IV or Beemer-Langer type
was retained as diagnosis . The differential diagnosis of this entity is
discussed .
P01.143
Ellis-Van creveld syndrome, with bilateral sensory-neural
hearing loss: report of a case and literature review
B. Bozorgmehr, F. Afroozan, V. Hadavi, M. H. Kariminejad;
Kariminejad-Najmabadi Pathology & Genetics Center, Tehran, Islamic Republic
of Iran.
Ellis-Van Creveld syndrome is a constellation of chondral, ectodermal
and cardiac defects . It is a rare autosomal recessive syndrome with
variable expression . This syndrome is also known as chondroectodermal
dysplasia and mesoectodermal dysplasia . The main features are
short stature, short ribs, polydactyly, dysplastic fingernails and teeth,
accompanied by heart defects . We are reporting a 2-year-old girl referred
to our genetics center with dwarfism, mesomelic short limbs,
narrow thorax, funnel chest, short ribs, oligodontia, oral frenula, postaxial
polydactyly of fingers and deafness. Her clinical findings are compatible
with Ellis-Van Creveld Syndrome . We believe that this is the
first Ellis-Van Creveld Syndrome with sensory-neural hearing loss.
P01.144
skeletal dysplasia with amelogenesis imperfecta- report of a
third family
O. Caluseriu 1,2 , M. Cholette 1 , M. A. Copete 3 , U. Amendy 1,2 , J. J. Howard 1,2 , R.
D. McLeod 1,2 ;
1 Alberta Children’s Hospital, Calgary, AB, Canada, 2 University of Calgary, Calgary,
AB, Canada, 3 Royal University Hospital, Saskatoon, AB, Canada.
Platyspondyly is a frequent feature in skeletal dysplasias, but an association
with amelogenesis imperfecta has only been reported twice .
Verloes and colleagues (1996) described two siblings of Moroccan
origin with consanguineous parents, who had mild growth retardation,
platyspondyly, dysplastic femoral necks, amelogenesis imperfecta and
oligodontia . They proposed their case to be a new subtype of brachyolmia
with amelogenesis imperfecta . A third case was described in a separate
paper (Houlston et al, 1994) . We present three additional cases
from a sibship of five. The affected children, two girls and a boy of 16,
9, and 12 years of age are non-dysmorphic and of normal intelligence .
They have short trunk short stature (-5SD, 3-10 centile and respectively
-3SD) with platyspondyly and oligodontia . The oldest girl has an
S shape scoliosis mid-thoracic to lumbar spine that required surgery
and bilateral coxa valga . The other two siblings have osteopenic bones
and lower thoracic-lumbar scoliosis . Recurrent dental abscesses were
noted and a subsequent diagnosis of amelogenesis imperfecta was
confirmed by dental pathology. The parents first cousins of Pakistani
origin are healthy and of normal stature . We provide further evidence
for a new AR previously proposed condition . Known genes involved in
amelogenesis imperfecta (including AR forms) do not explain concurrent
skeletal abnormalities .
P01.145
From a multimalformed baby to a new skeletal dysplasia
C. O. Barbosa 1 , D. P. Cavalcanti 2 ;
1 UNICAMP, Campinas, Brazil, 2 UNICAMP, Campinas - SP, Brazil.
In a number of cases skeletal dysplasias (SD) can be associated with
other malformations not related to the bone system, but usually the
diagnosis of SD is early after birth . In this presentation we report a
case of a multimalformed boy, firstly thought representing a VACTER
association, which afterward revealed an unusual skeletal dysplasia .
The infant was born at term by caesarean section weighting 2 .130 g,
46 cm height, and HC of 34 cm . Prenatal ultrasonography evaluation
showed oligohydramnios and absence of right kidney . Soon after birth
additional minor dysmorphisms and major anomalies were detected:
prominent metopic suture, up-slanting palpebral fissures, bilateral epicanthal
folds, ulnar deviation of 4 th -5 th fingers, syndactyly of the 2 nd -3 rd
toes, prominent calcaneus, esophageal atresia with distal fistula, mild
ventricular dilatation with tricuspid insufficiency and pulmonary hypertension,
dilated bile ducts, and moderate ventricular dilatation sugges-
tive of cerebral atrophy . No skeletal anomalies were observed at this
time . Karyotype was normal - 46,XY . Mental retardation was evident
in the follow up . At age of 6 years old short stature was evident . Bone
age was normal, but the skeletal findings showed findings of SD with
spondylo-epy-methaphyseal involvement and also some dyaphyseal
lesions . At this time the mother reported two maternal uncles with short
stature . As the skeletal lesions were suggestive of spondyloenchondrodysplasia,
hydroxyglutaric aciduria investigation was performed, but
results were normal . In conclusion, the patient here reported seems to
represent a new pattern of SD associated with mental retardation and
other no related skeletal anomalies .
P01.146
Further evidence for a recessive form of sEmD resembling
pseudoachondroplasia in a consanguineous family of
maghrebian origin
D. R. Amrom 1,2 , N. Van Regemoorter 3 , Y. Sznajer 4 , G. Jackson 5 , M. Briggs 5 , G.
Mortier 6 ;
1 Hôpital Français, Brussels, Belgium, 2 Center La famille, Brussels, Belgium,
3 Department of Medical Genetics, Hôpital Erasme – ULB, Brussels, Belgium,
4 Clinical Genetics, Hôpital Universitaire des Enfants Reine Fabiola – ULB,
Brussels, Belgium, 5 Wellcome Trust Centre for Cell-Matrix Research, Faculty of
Life Sciences, University of Manchester, Manchester, United Kingdom, 6 Department
of Medical Genetics, Ghent University Hospital, Ghent, Belgium.
Pseudoachondroplasia is an autosomal dominant disorder caused by
mutations of the COMP gene . In 2005, Spranger et al . described two
sibs with a spondyloepimetaphyseal dysplasia (SEMD) resembling
pseudoachondroplasia but without a COMP mutation . We have identified
a similar skeletal dysplasia in a dizygotic twin and maternal first
cousin, born to consanguineous parents of Maghrebian origin . They
presented around the age of 1 year with growth failure .
The proband is a 8-year-old girl with short-limb dwarfism (height at
-7sd) . She is of normal intelligence and has a normal head and face .
Clinical features include mild obesity, lumbar hyperlordosis, hyperlaxity
of finger and knee joints, metatarsus adductus and waddling gait.
Radiographic evaluation reveals mild anterior protrusion of the central
aspects of the vertebrae, abnormal pelvis with absent ossification of
the femoral epiphyses, shortened tubular bones with small epiphyses
and marked metaphyseal changes, and delayed carpal ossification.
Similar radiographic changes are observed in her twin brother who
in addition to short stature (height at -9sd) has microcephaly and tetraspasticity
of unknown origin. A maternal first cousin was referred
at the age of 7 years because of short stature (height at -3 .5sd) and
suspicion of pseudoachondroplasia . Sequence analysis of the COMP
gene did not reveal any mutation in this boy .
We believe that the three children in this consanguineous family have
the same skeletal dysplasia that resembles pseudoachondroplasia but
shows autosomal recessive inheritance . No mutation in the COMP
gene was identified suggesting a genetic defect in another gene important
in bone growth and development .
P01.147
Omani type spondyloepiphyseal dysplasia with cardiac
involvement caused by a new missense mutation in cHst3
B. Tüysüz 1 , S. Turkmen 2 , P. Nürnberg 2 , K. Sugahara 2 , A. Çelebi 1 , S. Mundlos 2 ;
1 İstanbul University, Cerrahpasa Medical Faculty Department of Pediatric Genetics,
İstanbul, Turkey, 2 Universitatsklinikum Berlin, Charite Virchow-Klinik,
Berlin, Germany.
We present three patients with a spondyloepiphyseal dysplasia,
brachydactyly and cardiac involvement in a large inbred Turkish family .
A genome wide scan using the 250K Affymetrix SNP chip revealed a
locus for homozygosity on chromosome 10q23 . This interval includes
an obvious candidate, Chondroitin 6-O-sulfotransferase-1 (C6ST-1)
gene (CHST3), previously shown to be mutated in Spondyloepiphyseal
Dysplasia (SED) Omani type. Focusing on CHST3, we amplified the
coding region of the CHST3 and identified a homozygous missense
mutation (T141M) in the exon 3 of the CHST3 gene in all three of the
affected members of the family . Using recombinant C6ST-1, it could
be shown that the identified missense mutation reduced the activity of
C6ST-1 to 24-29% . This is the second description of SED Omani type
further supporting this skeletal dysplasia as a distinct clinical entity .
Our patients shared the following features: short trunk stature, progressive
spinal involvement, brachydactyly, camptodactyly, irregular-
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