2008 Barcelona - European Society of Human Genetics

Clinical genetics
P01.138
clinical and molecular diagnosis of ADULt syndrome in a
pregnant woman
A. Wischmeijer1 , C. Graziano1 , M. Gnoli1 , R. Bocciardi2 , R. Ravazzolo2 , M.
Seri1 ;
1 2 U.O. Genetica Medica, Bologna, Italy, U.O. Genetica Molecolare e Citogenetica,
Genova, Italy.
A 29 year old woman affected by ectodermal dysplasia came to our
attention during her 1st pregnancy, asking about the risk of recurrence
in her children and the possibility of diagnostic prenatal testing .
No relatives were reported to be affected and the patient’s parents
were not consanguineous . Ectodermal dysplasia was suspected in
childhood because of hypodontia, corneal dystrophy, sparse hair, thin
skin and dystrophic nails, but a specific diagnosis had never been formulated
.
Upon clinical examination we noticed, besides classical signs, mild
dysmorphic features: deep-set eyes with upward-slanted and short
palpebral fissures, high forehead, low nasal bridge. Moreover, we
noticed bifid uvula, freckling and absence of nipples, which led us to
hypothesize involvement of the p63 gene . In fact, molecular analysis
of p63 identified the presence of a Gly134Val mutation, previously described
in a patient with ADULT syndrome . p63 mutations can give
rise to a spectrum of partially overlapping phenotypes, from ADULT
syndrome to limb-mammary and EEC syndrome, all transmitted with
an autosomal dominant pattern .
Absence of the mutation in the parents proved its de novo origin . Our
patient underwent CVS for fetal molecular analysis and, fortunately,
the mutation was not transmitted to the fetus .
Due to limited time availability, it is seldom possible to successfully
resolve a molecular diagnosis during pregnancy without preconceptional
analysis . Thanks to careful clinical examination, the availability
of an efficient laboratory and prompt familial involvement, our proband
received the result of prenatal testing in less than one month from the
1st counselling session .
P01.139
Variable expression in a familial case of Pfeiffer syndrome with
FGFR1 P252R mutation
K. Ludwig1 , C. Daolio1 , L. Salviati1 , M. Baldi2 , I. Mura2 , M. Clementi1 , R. Tenconi1
;
1 2 Servizio di Genetica Clinica, Padova, Italy, Laboratorio di Genetica, E.O.
Ospedali Galliera, Genova, Italy.
A 4 year and six month old boy was diagnosed with Pfeiffer syndrome
on the basis of bilateral coronal craniosynostosis, skin syndactyly of
toes, brachydactyly, broad thumbs and big toes and characteristic facial
dysmorphisms .
Close examination of the patient’s family revealed flattening, bilateral
soft tissue hypertrophy, foreshortening and medial deviation of
the great toes as well as mild bilateral proptosis in the mother and in
the older brother . The brother also had partial skin syndactyly of toes,
broad thumbs and camptodactyly of the left fifth finger. Neither the
mother, nor the brother showed any signs of craniosynostosis .
Molecular analysis of the FGFR1 gene revealed the P252R mutation
in all three family members .
Several articles have documented the high clinical variability and genetic
heterogeneity in individuals affected by Pfeiffer syndrome .
As far as we know this is the first case of an affected family with the
common FGFR1 P252R mutation in which just the proband has the
full-blown syndrome, whereas the other two affected persons show
characteristic feet anomalies without skull involvement, underlining the
broad intrafamilial variability of expression .
P01.140
molecular analysis of a case of Pfeiffer syndrome
M. Nateghi, M. Rostami, T. Majidizadeh, M. Dehghan Manshdi, M. Houshmand;
Special Medical Center, Tehran, Islamic Republic of Iran.
Pfeiffer syndrome is a rare autosomal dominantly inherited osteochondrodysplasia
with craniosynostosis conditions that is genetically heterogeneous
that can be caused by mutations in the fibroblast growth
factor receptor 2 (FGFR2) gene . The FGFR2 gene provides instructions
for making a protein called fibroblast growth factor receptor 2.
More than 20 FGFR2 mutations that cause Pfeiffer syndrome have
been identified. Several of these mutations change the number of cysteine
amino acids in a critical region of the FGFR2 protein known as
the IgIII domain .
Sporadic cases of Pfeiffer syndrome have previously been associated
with advanced paternal age .
The patient in our study was a 2 years old male baby . His parents were
healthy both under 25 years and they were not consanguineous . Labor
began spontaneously and the infant was delivery vaginally at term with
a birth weight of 2,975 g with the Apgar score of 8-9 . The propositus
had a cloverleaf skull, severe exorbitism, choanal atresia, low-set and
posteriorly-rotated ears, broad and medially-deviated halluces and
partial cutaneous syndactyly of the second and third toes . The ocular
globes and eyelids were intact with shallow orbits that would have
prevented the replacement of the eye . The ocular anterior structures
were preserved, without iris or lens abnormalities . The baby developed
respiratory distress .
Molecular analysis of the patient revealed a heterozygous C342R mutation
in exon 10 and a missense T→ C in mRNA further studies on
such sporadic cases recommended enhancing the molecular information
.
P01.141
combination of saethre-chotzen and Greig syndromes in one
family: the phenotype of a proband
S. Holubeva1 , N. Rumyantseva2 ;
1 2 Vitebsk Regional Diagnostic Center, Vitebsk, Belarus, Belarusian Medical
Academy of Postgraduate Education, Minsk, Belarus.
We present a female child (5-year-old), from a family with the features
of cephalopolysyndactyly (Greig syndrome) in her mother (30-yearold),
and acrocephalosyndactyly (Saethre-Chotzen syndrome) in her
father (28-year-old) and paternal grandfather (61-year-old) . Both syndromes
are autosomal dominant, minimal diagnostic criteria for the
first are syndactyly, polydactyly and cranial anomalies, for the second
- cranial synostosis with skull asymmetry, 2-3 toes syndactyly . The
mother’s phenotype consisted of cranial anomalies (protrudent frontal
tubers, hypertelorism, wide bridge of the nose), anomalies of extremities
(postaxial polydactyly of the right hand; moderately wide nail
bones of the first fingers of both hands; preaxial polydactyly and full 1-
2-3 toes syndactyly of the right foot; preaxial polydactyly with total toes
hypoplasia and full 1-2-3 toes syndactyly of the left foot) . Clinical features
of both the father and the grandfather included macrocephalia,
facial asymmetry, nasal septum deviation, partial 2-3 toes syndactyly .
The child showed a combination of cranial anomalies (macrocephalia,
facial asymmetry, nasal septum deviation, antimongoloid slant, wide
bridge of the nose), epicanthus of both eyes, low-set ears, anomalies
of extremities (postaxial polydactyly, preaxial polydactyly with full
syndactyly and common nail plate of both hands; postaxial polydactyly,
partial 2-3 and 4-5 toes syndactyly, full 3-4 toes syndactyly of the
right foot; postaxial polydactyly and full 2-3-4 toes syndactyly of the left
foot) . Thus, the proband has inherited the signs of both syndromes,
this means realization of their 50% of probabilities. The fact significantly
increases the risk for further generations, which should be taken
into account during genetic counseling .
P01.142
short rib-polydactyly syndrome on three consecutive
pregnancies
N. B. Abdelmoula1 , M. Trifa2 , H. Amouri1 , H. Amouri3 , R. Badraoui1 , R. Louati1 ,
F. Kallebi1 , T. Rebai1 ;
1 2 Medical University, Sfax, Tunisia, Urology of Private Sector, Sfax, Tunisia,
3Department of Gynecology, Sfax, Tunisia.
Short rib polydactyly syndromes are lethal skeletal dysplasias with an
autosomal recessive inheritance pattern that can be distinguished on
radiological and histological grounds . We report on three consecutive
pregnancies complicated by a short rib-polydactyly syndrome that was
difficult to categorize. Parents from North of Africa were consanguineous
(second degree) . The third fetus aborted at 22 weeks’ gestation
because of abnormalities visualized on sonography, has been radiologically
and histologically explored .
He presented shortened ribs with thoracic hypoplasia, short limbs with
postaxial polydactyly of hands and feet, cystic hygroma and facial dysmorphism
.
The skeletal changes observed included shortened ribs and shortened