2008 Barcelona - European Society of Human Genetics

Clinical genetics
tilation syndrome (CCHS) is a broad dysautonomia with predisposition
to Hirschsprung disease and NB in 20% and 5-10% of the cases respectively.
The identification of the PHOX2B gene as disease causing
in CCHS allowed to find that PHOX2B could be mutated in some familial
and sporadic cases of NB also. In order to find genes involved in
NB predisposition, we collected syndromic NB cases . Here we report
a series of 14 patients with hypoventilation and HD . Hypothamic dysfunction
is characterized by obesity, hyperprolactinemia, central hypothyroidism,
disordered water balance, unresponsive growth hormone
to stimulation test, corticotrophin deficiency and abnormal puberty be
it precocious or delayed . Up to now, all reported cases (25) have been
sporadic . The natural history of the syndrome is striking : rapid onset
obesity due to hyperphagia is the first symptom, followed by hypoventilation
with a mean delay of 1 .5 year . Neurocognitive deceleration and
mood disorders are frequently noted . The outcome remains poor in
this group of patients and would benefit from early diagnosis in order
to anticipate ventilation and possible metabolic disorders . Tumour predisposition
is as high as 4/14 (29%) in this series . Finally, we report a
familial case with recurrence in siblings and discuss a paraneoplastic
syndrome an autoimmune disorder and a monogenic condition .
P01.303
Neonatal data on 530 children born after icsi using testicular
spermatozoa
F. De Schrijver1 , H. Tournaye2 , I. Liebaers1 , P. Devroey2 , P. Haentjens1 , M.
Bonduelle1 ;
1 2 center for medical genetics, Brussels, Belgium, center for reproductive medicine,
Brussels, Belgium.
INTRODUCTION: We analysed pregnancy outcome and neonatal
data of children born from a consecutive cohort of ICSI cycles performed
with testicular spermatozoa .
MATERIAL & METHODS : Questionnaire data and results of physical
examinations on 530 ICSI children from azoospermic fathers from
whom testicular spermatozoa were obtained (period 1994-2007) were
compared with control data from 2889 ICSI children . All children were
examined by a geneticist during their first year of life.
A subanalysis of outcome parameters was performed in relation to the
cause of azoospermia .
RESULTS: Of the 657 pregnancies obtained after ICSI using testicular
spermatozoa, 426 (63 .1%) were ongoing after 20 weeks leading to
the birth of 530 liveborn children: 331 singletons, 178 twins and 21
triplets . Mean birthweight, length and head circumference as well as
prematurity, low birthweight and perinatal mortality in singletons and
twins did not differ from the ICSI control group . No increase in major
malformations was observed in liveborn TESE children (4 .90%) when
compared to the control ICSI group . Prenatal (126) and postnatal (72)
karyotype analysis revealed 2 .02% de novo abnormalities and 0 .51%
inherited abnormalities compared to 0 .45% de novo anomalies (OR
4 .57; 95%CI 1 .68-12 .38) in the general newborn population .
Further subanalysis in relation to the cause of azoospermia did not
reveal any differences in neonatal outcome parameters and major
malformations rate .
CONCLUSIONS: Neonatal outcome and major malformations rate
were similar in TESE children compared with a control cohort of ICSI
children but more de novo chromosomal anomalies were found compared
to the general newborn population .
P01.304
A case with interstitial deletion of 11q
D. Niedrist 1 , M. Riegel 1 , A. Baumer 1 , P. Miny 2 , A. Schinzel 1 ;
1 Institute of Medical Genetics, University of Zurich, Schwerzenbach-Zurich,
Switzerland, 2 Division of Medical Genetics, University Children’s Hospital, Basel,
Switzerland.
We report on a 12 year-old boy with mental retardation (EQ 45), cleft
palate, umbilical and unilateral inguinal hernia and discrete dysmorphic
features: low frontal hairline, red hair with multiple whorls and
unusual growth pattern, flat occiput, low set ears with poorly formed
helices, narrow auditory canals, full eyelids, up-slanting palpebral fissures,
prominent lips, small mandible, narrow sloping shoulders, discrete
pectus excavatum, inverted nipples and abnormal distribution of
fat tissue over the proximal forearms . On the upper limb there were
proximal placement of thumbs, restricted flexion in all metacarpo-phalangeal
joints, prominent finger pads and short and broad nails and
distal phalanges . On the lower limb there were diminished stability in
the knees and pes planus . The boy had a good social behaviour and
pleasant nature .
Karyotype revealed an interstitial deletion involving 11q14 . By arrayC-
GH the deletion could be further defined to 11q13.5->11q14.3.
We compared our case with case reports with similar sized deletions
involving the bands 11q13 and 11q14. Similar phenotypic findings included
mental retardation, normal measurements at birth, low frontal
hairline, dysmorphic ears, full eyelids or ptosis, small mandible, high
arched or cleft palate and minor features of the fingers, thumbs or toes.
In interstitial deletion 11q the facial gestalt and the incidence of joint
limitations is similar to Williams-Beuren syndrome, whereas in contrast
to Williams-Beuren syndrome the retardation in speech is more
pronounced and there is in general no heart defect, growth retardation
or microcephaly .
P01.305
A novel case of partial trisomy 2p in a 2-year old girl
S. Unlubay 1 , O. Cogulu 2 , B. Durmaz 2 , A. Alpman 1 , F. Ozkinay 2 ;
1 Ege University Faculty of Medicine Department of Medical Genetics, IZMIR,
Turkey, 2 Ege University Faculty of Medicine Department of Pediatrics, IZMIR,
Turkey.
The characteristics of partial duplication of the short arm of chromosome
2 have been documented in different reports . The clinical phenotype
of trisomy 2p includes growth and psychomotor retardation,
microcephaly, prominent forehead, hypertelorism, epicanthal folds,
ptosis, strabismus, myopia, apparently low set and abnormal ears,
flat nasal bridge, narrow high palate, micrognathia, sternal abnormalities,
epileptic seizures, kyphoscoliosis, congenital heart disease,
genital hypoplasia, long widely spaced fingers and toes and hypotonia.
Here, we report on a new case of inv dup 2p in a 2 year-old girl . She
was born to no non-consanguineous parents after an uncomplicated
pregnancy . The birth weight was 2 .800 kg . The physical examination
revealed generalized hypotonia, pectus excavatum, frontal bossing,
flat nasal bridge, hypertelorism, low-set and large ears, micrognathia,
syndactyly in the 2-3-4 toes . She also had severe growth and
psychomotor retardation. At 6 months, she had the first epileptic seizure
and three more seizures occurred afterwards . The EEG showed
abnormal discharges . She also had recurrent respiratory infections .
Her thorax CT scan showed subsegmental atelectasis in the posterior
lobes and areas of bronchiolitis obliterans. Gastroesophageal reflux
was determined in the scintigraphy . The cranial MRI was normal . The
karyotype revealed a partial trisomy of chromosome 2p and was noted
as 46,XX,inv dup(2)(p23p25 .2) . The parents had normal karyotypes .
According to the clinical picture and the karyotype, the patient was
considered to be a novel case of partial trisomy 2p and fluorescence in
situ hybridization (FISH) and array comperative genomic hybridisation
(aCGH) studies were planned for revealing the exact breakpoints .
P01.306
clinicopathological study of a infantile systemic Hyalinosis case
with a novel mutation in the CMG gene
B. Demeer 1 , M. M.Viprey-Thouvard 2 , M. Ramirez 3 , N. Bednarek 2 , M. Doco-
Fenzy 1 , M. Abely 2 , J. Martignetti 3 , D. Gaillard 1 ;
1 Department of Genetics, Reims Hospital, reims, France, 2 Department of Pediatrics,
American Memorial Hospital, reims, France, 3 Department of Human
Genetics, Mount Sinai School of Medicine, NY, United States.
Infantile Systemic Hyalinosis (ISH) is an autosomal recessive disorder,
belonging to the wide and heterogeneous group of genetic fibromatosis,
characterized by widespread deposition of hyaline material in
the skin, gastrointestinal tract, muscles and glands . Mutations in the
capillary morphogenesis gene-2 (CMG2), coding for a transmenbrane
protein with important roles in cell-cell adhesion and cell-extracellular
matrix interactions, have been shown to cause ISH . We report on a
patient with a severe form of ISH, confirmed by clinical and histological
findings, who also displayed clear evidence of early muscle involvement,
and enteropathy . Novel mutation of CMG2 gene has been found
and review of the litterature will be made .
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