2009 Vienna - European Society of Human Genetics

Clinical genetics and Dysmorphology
joint contractures, dysplastic clavicles and thin ribs were also noteable.
He died on 14 days of his life from respiratuar distress. The patient was
diagnosed as Restrictive Dermopathy which is a rare, lethal autosomal
recessive disorder characterized by; tight and rigid skin with erosions,
prominent superficial vasculature and epidermal hyperkeratosis, small
mouth, small pinched nose, micrognathia, sparse or absent eyelashes
and eyebrows and joint contractures. Restrictive dermopathy is caused
by the mutations in the zinc metalloproteinase gene ZMPSTE24 or
LMNA. Analysis by direct sequencing of the gene ZMPSTE24 was performed
and a single base insertion on exon 9 was identified in the patient
on homozygous state (c.1085_1086insT) leading a null mutation
(p.Leu362PhefsX19). The parents latter demanded genetic consultation
for next pregnancy. Found mutation on ZMPSTE24 was searched
on the DNA derived from corionic villi specimen and seen that the fetus
inherited normal allels form both of the parents.
P02.101
Restrictive dermopathy in two siblings caused by novel
compound heterozygous mutations of the ZmPstE24 gene
R. Smigiel 1 , A. Jakubiak 1 , V. Esteves-Vieira 2 , K. Szela 3 , A. Halon 4 , T. Jurek 5 , N.
Lévy 6 , A. De Sandre-Giovannoli 7 ;
1 Genetic Department Wroclaw Medical University, Poland, Wroclaw, Poland,
2 Laboratoire de Génétique Moléculaire, Département de Génétique Médicale,
Hôpital d’Enfants la Timone,, Marseille, France, 3 Newborns and Premature
Infants Ward, Specialist Mother and Child Health Care Unit, Opole, Poland,
4 Pathomorphology Department, Wroclaw Medical University, Wroclaw, Poland,
5 Forensic Medicine Department, Wroclaw Medical University, Wroclaw, Poland,
6 Laboratoire de Génétique Moléculaire, Département de Génétique Médicale,
Hôpital d’Enfants la Timone, Marseille, France, 7 Inserm UMR_S 910, « Medical
Genetics and Functional Genomics », Faculté de Médecine de Marseille,
Marseille, France.
Restrictive dermopathy (RD) is a rare, lethal disorder caused by mutations
in the ZMPSTE24 gene (autosomal recessive) or in the LMNA
gene (autosomal dominant). To date, about sixty cases of RD have
been described. The signs of RD are very characteristic and include
intrauterine growth retardation, thin, tight skin, superficial vessels, typical
face changes and joint contractures. Children die within the first
week of life. We observed the recurrence of the disease in a Polish
family and report the identification of two novel inactivating ZMPSTE24
mutations. The children showed respectively, during the prenatal period:
IUGR, decreased fetal movements, polyhydramnios, for the first
child, and normal pregnancy to 30 weeks of gestation for the second.
At premature delivery (32 and 33 weeks of gestation) both children
showed typical facial features: hypertelorism, down-slanting palpebral
fissures, pinched nose, posterior rotated ears, micrognathia, mouth in
“o” position, skin and skeletal anomalies: thin and rigid skin with erosions
and scaling, prominent superficial vessels, multiple joints contractures,
camptodactyly, absent and small nails, rocker-bottom feet
and narrow chest. Biological material was available for the second
child: skin histology revealed thinned epidermal layers, focal hyperorthokeratosis,
partial parakeratosis. Hair follicles and sebaceous glands
were immature and poorly developed. The dermis showed absence
of elastic fibers. Molecular analyses could be performed on the second
child and his parents. Two novel, compound heterozygous, inactivating
mutations of the ZMPSTE24 gene were observed in exon 1
(c.50delA; p.K17SfsX21) and 5 (c.584_585delAT; p.Y195Ffs22X). The
autosomal recessive inheritance was confirmed by the parents’ molecular
analysis.
P02.102
sc phocomelia/Roberts syndrome spectrum - A case Report of
an Adult with Review of the Literature
C. Morel1 , E. Goh2 , E. Kolomietz3 ;
14 University Health Network and Mount Sinai Hospital, Toronto, ON, Canada,
2 3 Hospital for Sick Children, Toronto, ON, Canada, Mount Sinai Hospital, Toronto,
ON, Canada.
Roberts syndrome (RBS) (OMIM #268300) is a rare autosomal recessive
disorder characterized by tetraphocomelia (symmetrical limb
reduction), craniofacial anomalies, growth retardation, mental retardation,
cardiac and renal abnormalities. Karyotype investigations
in affected patients characteristically reveal premature centromere
separation, or heterochromatin repulsion. The syndrome is caused by
mutations in the ESCO2 gene, which is located at locus 8p21.1, and
encodes a protein essential in establishing sister chromatid cohesion
during S phase. Allelic to this condition is SC phocomelia (SC) (OMIM
#269000), which has a milder phenotype compared to RBS with less
severe symmetric limb reduction, flexion contractures of various joints,
minor facial anomalies, growth retardation and occasionally, mental
retardation. Individuals with SC typically survive to adulthood whereas
severely affected RBS infants may be stillborn or die in the post-natal
period. As a result, there is little literature about the follow-up of
adults with the spectrum of SC phocomelia/Roberts syndrome or the
recommended management. We report an adult presentation of SC
phocomelia/Roberts spectrum disorder with a history of major cardiac
malformation in childhood, mild facial anomalies, normal intelligence
and premature centromere separation. A literature review is presented
focussing on adult manifestations of this condition. Finally, we establish
follow-up guidelines based on the reviewed cases.
P02.103
is schinzel-Giedion syndrome a genomic disorder?
G. M. S. Mancini 1 , R. Schot 1 , P. J. Poddighe 1 , R. de Coo 2 , A. Schinzel 3 ;
1 Clinical Genetics, ErasmusMC, Rotterdam, The Netherlands, 2 Child Neurology,
ErasmusMC, Rotterdam, The Netherlands, 3 Medical Genetics, University of
Zurich, Zurich, Switzerland.
Schinzel-Giedion syndrome (SGS) is a severe neuro-developmental
disorder characterized by distinctive face, short stature, limb abnormalities,
sclerosis of the basis of the skull, wormian bones, gap in occipital
skull, broad ribs, curved long bones and hypoplastic phalanges.
Hydronephrosis, congenital heart defects and urogenital anomalies
have been described. Inheritance is considered autosomal recessive.
A boy was observed in 1997 after birth for short stature, hydronephrosis,
mild pulmonic stenosis, unilateral cryptorchidism and limbs abnormalities.
He developed obstructive apnoeas and swallowing difficulties.
At the age of 18 months he was still short with hypotonia, pyramidal
signs, epilepsy with multifocal EEG anomalies, no eye contact, high
myopia, nasolacrimal duct stenosis, a large fontanel, high forehead,
hypertelorism, midface hypoplasia, arched eyebrows with synophrys,
chubby cheeks, broad nose, large mouth and protruding tongue, low
set dysplastic ears, cochlear deafness, short neck, brachydactyly and
abnormal creases, short broad 1 st toe and generalized hirsutism. Brain
MRI showed an empty sella. X-rays showed wormian bones, no sclerosis
of the skull, short hand phalanges. His karyotype was 46,XY.
At that time Schinzel-Giedion syndrome was diagnosed. In 2008 Affy
250K NspI arrays showed a submicroscopic der(9)t(9q34;17q25). This
represents one of the largest 9q34 microdeletions described, probably
explaining the severe phenotype. Hirsutism, hydronephrosis and severe
neurological phenotype are typical of SGS and unusual for 9q34
deletions. Our observation, however, arises the question whether at
least some SGS patients might have a cryptic chromosomal imbalance
or, less likely, whether some of the genes on 9q34 in our patient
contain a second recessive mutation.
P02.104
Novel Findings By Genome-wide copy Number Analysis on
chromosome 22 in a case with mild Facial Dysmorphology and
Autistic/schizophrenic Behaviours
E. Pariltay, O. Cogulu, A. Aykut, A. Alpman, B. Ozbaran, S. Erermis, C. Aydin,
F. Ozkinay;
Ege University, Faculty of Medicine, Izmir, Turkey.
Autism and schizophrenia are two neuro-psychological disorders
which may occur superimposed on each other. They can be accompanied
with some dysmorphic syndromes such as Fragile X syndrome,
Williams syndrome and Down syndrome. We present a 13-year-old
female case who showed autistic symptoms at first and followed by
positive schizophrenic symptoms. She also had multiple mild dysmorphic
features such as elfin-like facial features, arched eyebrows, hypertelorism,
depressed nasal bridge, bulbous nasal tip, downturned
corners of mouth, thick lower lip and joint laxity. Karyotyping and FISH
for Williams, Angelman and subtelomere of 22q were performed. We
performed whole genome copy number analysis by Affymetrix Gene
Chip 6.0 array for both case and parents. We showed inherited copy
number variations without any additional region. We also performed
LOH analysis and showed ~ 7Mb homozygosity at 22q11.
No dysmorphic syndrome was identifiable; therefore she could be an
example of an unusual clinical picture with positive autistic, psychotic