2008 Barcelona - European Society of Human Genetics

Clinical genetics
P01.133
White matter abnormalities in siblings with Goldberg shprintzen
syndrome
J. Pilch 1 , J. D. H. Jongbloed 2 , E. Kluczewska 3 , P. M. Grootscholten 2 , E. Emich-
Widera 1 , E. Marszał 1 ;
1 Department of Child Neurology, Medical University of Silesia, Katowice, Poland,
2 Departments of Genetics, UMCG, University of Groningen, Groningen,
The Netherlands, 3 Department of Radiology Zabrze, Medical University of Silesia,
Katowice, Poland.
Goldberg Shprintzen syndrome (OMIM 609460, GOLDBERG-
SHPRINTZEN MEGACOLON SYNDROME - GOSHS) is rare syndrome
of congenital malformations with autosomal recessive pattern
of inheritance . The most frequent manifestations are: mental
retardation, microcephaly with accompanying dysmorphic features,
and Hirschsprung disease . The syndrome is a result of mutations in
KIAA1279 gene, which function is still poorly understood . It is possible
that incorrect function of the gene product is a cause of abnormal migration
of neurons, thus in addition to Hirschsprung disease, a brain
developmental defects e .g . polymicrogyria, pachygyria or agenesis of
corpus callosum is observed . There is just few reports in the literature
describing GOSHS, including one reporting an abnormal intensity of
white matter signals . Her we report two brothers with GOSHS symptoms
and mutation fund in KIAA1279 gene . The MRI revealed in one
patient evidence of cranio-facial dysmorphy, asymmetry and dilatation
of the ventricular system, and partial agenesis of corpus callosum . Additionally,
in both patients discreet stranded regions of high intensity
signals along the Roland’s sulci, in the both internal capsules and lateral
parts of the thalamus were found . Also, in both patients abnormal
values of evoked potentials were observed . The clinical symptoms
were variable in GOSHS, similarly like in most such syndromes . In one
patient the features of Hirschsprung’s disease did not occur but in the
other one they were of mild intensity . Changes in the MRI pattern of the
brain not seen in this syndrome until now and systematic description
of clinical features are valuable additions to clinical characterization
of GOSHS .
P01.134
two new cases of Hajdu-cheney syndrome and further
syndrome delineation
R. Posmyk 1 , K. Kozłowski 2 , E. Hubert 3 , A. T. Midro 1 ;
1 Department of Clinical Genetics, Medical University, Bialystok, Poland, 2 Royal
Alexandra Hospital for Children, Sydney, Australia, 3 Maxillo-Facial Surgery
Clinic, Medical University, Bialystok, Poland.
Hajdu-Cheney syndrome (HCS) (102500#OMIM) is a rare disorder
characterised clinically by small stature and distinctive face . Diagnostic
radiographic features consist of acro-osteolysis and unique dysplastic
skull changes . We report on two new HCS cases a 9 and 16year-old
boys full filing inclusion criteria by Brennan and Pauli (2001).
A detailed phenotype description of each boy is given and evaluated
together with 23 other published case reports with the aim to delineate
the spectrum of clinical and anthropological features . A catalogue of
nearly 900 well-defined traits according to Stengel-Rutkowski et all
(1996) with own modification was used. Sixty dysmorphological, clinical
and radiographic features were put into the quantitative phenotype
definition of HCS syndrome. Additionally, a variety of clinical (hearing
loss, vocal scale limited to lower tones, delayed fontanels closure, delayed
dental eruption, open bite, depressed sternum) and radiological
findings (Wormian bones, acro-osteolysis, generalized osteoporosis)
were taken into account . As molecular basis of this entity remains unknown,
we believe that quantitative phenotype definition of HCS can
be helpful for early diagnosis, before acro-osteolysis, the decisive diagnostic
sign, develops .
P01.135
Familial Hanhart Syndrome in a Newfoundland Kindred
C. Li;
McMaster University Medical Center, Hamilton, ON, Canada.
Hanhart syndrome, also known as oligodactyly-hypoglossia, adactylyaglossia
or oromandibulo limb hypoplasia syndrome because of the
cardinal signs of limb and tongue anomalies associated with abnormal
mandibular development, is a rare genetic condition that usually happens
sporadically and is assumed to be the consequences of either a
vascular disruption event or a new dominant mutation . A Newfound-
land kindred spanning 4 generations is believed to have this condition
where affected members manifest ulnar ray defects, oligodactyly and
ankyloglossia with highly variable expressivity amongst the affected .
Development, intelligence, stature and overall health are normal for
these individuals. To my knowledge, this is the first report of familial
cases of this genetic condition. It’s presence confirms autosomal dominant
inheritance as one underlying etiology .
P01.136
Holt-Oram syndrome - case report
M. C. Panzaru, C. Rusu, M. Volosciuc, M. Covic;
Medical Genetics Centre, Iasi, Romania.
Holt-Oram syndrome (HOS) is an autosomal dominant condition with
variable expressivity characterized by the association of congenital
heart defects and preaxial radial ray upper limb defects . We present a
new case in order to illustrate this rare entity and to discuss the variable
expression and the management . Our proband is a 13,5 old male,
the only child of an unrelated couple . Father presents absence of the
left thumb, short left limb, cardiac failure . No fetal ultrasound scan was
performed . The proband was born naturally at 37 weeks gestation (Wt-
2450g, Ht-46,5cm, HC-36 cm, Apgar score 7) . Postnatal development
was relatively normal . Physical examination (13y old) revealed: Wt -
2,52 SD, short limbs with absence of forearms, bilateral absence of
thumbs, absence of left forefinger. Radiological examination showed
bilateral absence of radius and ulna . Echocardiography: ASD ostium
secundum; ECG: first-degree atrioventricular block. We have established
the diagnosis of HOS based on the characteristic association
of congenital heart defects and upper limbs defects . Differential diagnosis
was done with other heart-hand syndrome . The plan for the
management and the genetic counseling will be presented . In conclusion,
we present a case of HOS in order to illustrate this rare genetic
disorder but also to discuss the variable expression, the management
and the genetic counseling .
P01.137
Spinal abnormalities, Klippel-Feil syndrome and the Mayer-
Rokitansky-Küster-Hauser syndrome: four case reports
T. Rebai, R. Badraoui, F. Kallebi, R. Louati, N. B. Abdelmoula;
Medical University, Sfax, Tunisia.
The Mayer-Rokitansky-Küster-Hauser (MRKH) syndrome is characterized
by congenital aplasia of the uterus and the upper part (2/3) of the
vagina and is regarded as an inhibitory malformation of the Müllerian
ducts . MRKH may be isolated but it is more frequently associated with
renal, vertebral, and, to a lesser extent, auditory and cardiac defects
(MURCS association) . The molecular basis for the MRKH syndrome
is currently unknown .
We describe four female patients in whom diagnosis of MRKH syndrome
was confirmed. All complained of primary amenorrhea associated
with cyclic pelvic pain and presented normal sexual development,
normal levels of FSH, LH and 17beta estradiol, 46,XX karyotype and
congenital absence of the uterus and upper vagina .
The first patient presented short neck, low-set posterior hairline, limited
neck motion and fusion of cervical vertebrae associated with unilateral
elevated scapula .The second patient presented low-set posterior
hairline, short neck with very limited neck motion and fusion of cervical
vertebrae associated with unilateral elevated scapula, cyphoscoliosis,
asymmetrical breast development, dental abnormalities and flat feet.
A familial history with a Sister complaining of secondary amenorrhea
with low-set posterior hairline, minor scoliosis and flatfeet, was recorded
. The described skeletal deformity in these 2 females, were consistent
with Klippel-Feil syndrome .
The third patient presented low-set posterior hairline, short neck,
shield-like chest and scoliosis . She presented also dental deformities,
cafe-au-lait spots and many nevus spilus and vascularis . An history
of two azoospermic maternal uncles was recorded . The forth patient
presented a minor scoliosis and asymmetrical hips .