European Human Genetics Conference 2007 June 16 – 19, 2007 ...

Clinical genetics
P0161. Intrafamilial phenotypic variability in Malpuech
Syndrome: Report of Three Siblings and a Review.
T. Ben-Omran 1 , M. Almureikhi 1 , A. Teebi 2 ;
1 Section of Clinical and Metabolic Genetics, Department of Pediatrics, Hamad
Medical Corporation, Doha, Qatar, 2 Department of Pediatrics, Weil- Cornell
Medical College, Doha, Qatar.
We report on three sibs (2 girls, one boy) with Malpuech syndrome,
born to a phenotypically normal first cousin Qatari Arab parents. This
is an extremely rare autosomal recessive syndrome first described in
1983 by Malpuech et al., with few (13) patients reported so far. It is
characterized by facial clefting, hypertelorism and ptosis; malar hypoplasia,
urogenital anomalies, caudal appendage and sacral dimple;
and growth and mental retardation. All three sibs showing the range of
anomalies found in Malpuech syndrome. They have growth and mental
retardation, facial dysmorphism including ptosis, thick eye brows
and flat malar region; and eye abnormalities. In addition, one sister
and the brother have hypertelorism, caudal appendage, and bilateral
cleft lip and palate and pseudocleft respectively. While expression of
the syndrome was relatively mild in the older sister, the brother and
the younger sister showed the full-blown syndrome. This family further
supports the autosomal recessive inheritance for this syndrome.
The constellation of clinical manifestations in this sibship emphasizes
the phenomenon of intrafamilial variability that may lead to difficulty in
diagnosis. We will review the previously published reports and further
expand the phenotype of this rare condition. Attention is drawn to the
clustering of such rare syndromes in this area.
P0162. Clinical factors associated with the occurrence of an
aortic dilatation within a cohort of 1013 patients with Marfan
syndrome or another type I fibrillinopathy
L. Faivre 1 , G. Collod-Beroud 2 , B. Loeys 3 , A. Child 4 , C. Binquet 5 , G. Elodie 5 , B.
Callewaert 3 , E. Arbustini 6 , K. Mayer 7 , M. Arslan-Krichner 8 , P. Comeglio 4 , C. Beroud
9 , C. Bonithon-Kopp 5 , M. Claustres 9 , L. Ades 10 , J. De Backer 3 , P. Coucke 3 ,
U. Francke 11 , A. De Paepe 3 , C. Boileau 12 , G. Jondeau 13 ;
1 Departement de Genetique, Dijon, France, 2 INSERM U827, Montpellier,
France, 3 Medical Genetics, Ghent, Belgium, 4 St George’s Hospital, London,
United Kingdom, 5 CIC-EC, Dijon, France, 6 Policlinico San Matteo, Pavia, Italy,
7 Human Genetics, Martinsried, Germany, 8 Institut fur Humangenetik, Hannover,
Germany, 9 Génétique Moléculaire, Montpellier, France, 10 Marfan research
group, Sidney, Australia, 11 Genetics and Pediatrics, Stanford, CA, United
States, 12 Génétique Moléculaire, Ambroise Paré, Boulogne, France, 13 Centre de
Référence Marfan, Hopital Bichat, Paris, France.
The cardinal features of MFS involve the ocular, cardiovascular and
skeletal systems. Clinical care is complicated by variable age of onset
and the wide range of severity of aortic features. Taking advantage of
the data of a large collaborative study designed for a genotype-phenotype
correlation study including 1013 probands with a pathogenic
FBN1 mutation, we searched for clinical factors associated with the
occurrence of ascending aortic dilatation (AAD) over time. Probabilities
of AAD were described using Kaplan-Meier method and compared
using logrank tests according to the following clinical signs: 1) 5 or
more skeletal features of the MFS spectrum (n=272); 2) ectopia lentis
(n=542); 3) mitral valve prolapse (n=533); 4) striae (n=444); 5) pneumothorax
(n=73) or 6) dural ectasia (n=154). Baseline was considered
as the date of birth. Among the 1013 included probands, aged in median
of 29 years old (IQR [15-40]) at their last follow-up, 775 (77%)
had AAD. Ectopia lentis and pneumothorax were not significantly associated
with the risk of AAD. Striae and dural ectasia were associated
with a lower risk of developing an AAD (p=0.001 and p=0.03 respectively).
Conversely, patients with 5 or more skeletal features, or a mitral
valve prolapse had a higher risk of AAD (p