2008 Barcelona - European Society of Human Genetics

Clinical genetics
the likelihood of detecting VEGFR3 mutations is optimised . Mutation
prevalence is 72% in typical Milroy patients with a family history (group
I) and 64% if positive family history is not a diagnostic criterion . A positive
family history is not essential in Milroy disease . The likelihood of
detecting VEGFR3 mutations in patients who have a phenotype which
is not typical of Milroy disease is very small (C (R552G)) . However Marfan disease was not documented
with a negative screening of FBN1 gene . We discuss the hypothesis
of a pleiotropic effect of the SOS1 mutation, the influence of the
familial stature, and the eventuality of two concomitant independent
diseases .
P01.177
SOS and PTPN mutations in five cases of Noonan syndrome
with multiple giant cell lesions
C. Beneteau 1,2 , H. Cavé 3 , A. Moncla 4 , N. Dorison 5 , A. Munnich 6 , A. Verloes 3 , B.
Leheup 1,2 ;
1 Service de Médecine Infantile III et Génétique Clinique, Hôpital d’Enfants CHU
de Nancy, Vandoeuvre les Nancy, France, 2 Faculté de médecine Nancy Université
Henri Poincaré, Vandoeuvre les Nancy, France, 3 Département de Génétique
clinique, Hôpital Robert Debré, Paris, France, 4 Département de Génétique
Médicale, Hôpital d’enfants de la Timone, Marseille, France, 5 Neuropédiatrie
pathologie du développement, Hôpital Armand Trousseau, Paris, France, 6 Service
de Génétique Médicale, Hôpital Necker Enfants Malades, Paris, France.
We report five cases of multiple giant cell lesions in patients with typical
Noonan syndrome . Such association has been frequently referred to
as Noonan like-Multiple Giant Cell syndrome before the molecular definition
of Noonan syndrome . Three patients carry mutations in SOS1
(p .Arg552Ser and p .Arg552Thr) and two in PTPN11 (p .Tyr62Asp and
p.Asn308Asp) and are the first SOS1 mutations in Noonan like-Multiple
Giant Cell syndrome .
The five patients have typical features for Noonan syndrome. Congenital
heart diseases were diagnosed during gestation or after birth .
Radiograph and CT scan showed unilateral or bilateral mandibular radiolucencies
characteristic of cherubism for five patients with cherubic
appearance or incidentally discovered at systematic radiographic examination
. The other patient presented typical imaging and histopathological
signs of a left ankle pigmented villonodular synovitis . Three of
the five patients had short stature and three had learning disabilities.
They show two distinct phenotypes: Noonan with cherubinism and
Noonan with pigmented villonodular synovitis, demonstrating that both
clinical phenotypes are not PTPN11-specific anomalies and represents
a rare complication of overexpression of the RAS/MAPK signaling
pathway . We discuss the clinical overlap between Noonan syndrome,
Noonan like-Multiple Giant Cell syndrome, “true” cherubism and pigmented
villonodular synovitis . The two latter terms should be used only
when multiple giant cell lesions occur without any other evidence of
Noonan syndrome . Noonan like-Multiple Giant Cell syndrome previously
regarded as an entity distinct from Noonan syndrome is more
likely as a phenotypic variation within the Noonan spectrum .
P01.178
clinical study of a family with Noonan syndrome (Ns)
transmited from mother to daughter
L. I. Butnariu 1 , E. Gorduza 1 , D. Anton 2 , M. Covic 1 ;
1 *University of Medicine and Pharmacy “Gr. T. Popa”, Department of Human
Genetics, Iasi, Romania, 2 *University of Medicine and Pharmacy “Gr. T. Popa”,
“Saint Mary” Hospital, Iasi, Romania.
Noonan Syndrome (NS) is an autosomal dominant disease, with mutation
inherited essspecially from mother, characterized by typical facial
dysmorphism, short stature, heart defect, mental retardation and he-