2008 Barcelona - European Society of Human Genetics

Clinical genetics
P01.307
maternal uniparental isodisomy 20 : clinical report
C. Vincent-Delorme 1,2 , E. Pipiras 3 , S. Drunat 4 , C. Dupont 3 , A. Delahaye 3 , I.
Guilhoto 5 , S. Manouvrier 6 , B. Benzacken 3 ;
1 UF de génétique CH Arras.Service de Génétique clinique CHRU Lille, Arras,
France, 2 Centre de référence maladies rares pour les syndromes malformatifs
et anomalies de développement Nord de France, Lille, France, 3 UF de cytogénétique
Service HEC-BDR Hôpital Jean Verdier AP-HP, Bondy, France, 4 UF
de Biologie moléculaire Département de Génétique Hôpital Robert Debré AP-
HP, Paris, France, 5 Service de Médecine Néonatale CH Arras, Arras, France,
6 Service de Génétique clinique CHRU Lille. Centre de référence maladies rares
pour les syndromes malformatifs et anomalies du développement Nord de
France, Lille, France.
We report on a young child, presenting with intractable feeding difficulties,
and severe post-natal growth retardation required enteral tube
feeding,
He was the second child, from non-consanguinous Caucasian healthy
parents, born at 39 weeks of gestation and delivery was uneventful .
Birth measurements were normal .
Nucal translucency was detected during first trimester of pregnancy
and prenatal investigation in amniotic fluid was performed.
Chromosome studies using standard R banding showed a tiny marker
in all cells; parents refused complementary investigations .
Prenatal ultrason examination revealed moderate pyelectasy . Post-natal
examination showed posterior urethral valves .
Post-natal cytogenetic analysis revealed that the marker was from
chromosome 20 and contained only centromere and pericentromeric
segments .
The combination of cytogenetic findings and severe feeding difficulties
made we speculate that it could be a maternal UPD 20 confirmed by
molecular analysis .
Phenotype, in our case, is less severe (specially mental retardation)
than those of the paternal 20q13 .2-q13 .3 deletions, even though major
chararteristic are present .
At 3 years, measurements are- 5SD for length and weight, and -0,5SD
for OFC . He says only a few words and walks with help .
This report demonstrates interpretation’s difficulties when excedentary
marker is found and allows us to be careful, and to look for UPD for
markers derived from imprinted chromosomes .
P01.308
Hypomelanosis of ito - report of two patients
M. P. Martins, R. P. Leite, M. Souto, E. Ribeiro;
Centro Hospitalar Trás-os-Montes e Alto Douro, Vila Real, Portugal.
Hypomelanosis of Ito syndrome (HI - MIM* 300337), is characterized
by the presence of whirled hypochromic skin lesions often associated
with systemic manifestations .
To date, epidemiological data on HI are limited . It appears to be the
third most common neurocutaneous disease, second only to neurofibromatosis
and tuberous sclerosis . Approximately three fourths of the
patients with typical skin lesions have systemic manifestations . Typical
skin lesions are initially demonstrated during the first year of life
in as many as 70% of patients; they are noticeable at birth in 54% of
patients . Prognosis depends on the patient’s manifestations and complications
of the disease . Patients with chromosomal anomalies are at
risk for tumors .
We report two children, a 6 years female and a 5 years old male, with
typical HI lesions and systemic nondermatological abnormalities (eg,
mental retardation and epilepsy) . Blood karyotyping was normal on
both; skin biopsy revealed normal fibroblast karyotype in the girl and
mosaicism for chromosome abnormality in the boy .
Despite recent advances, the genetic substrate for HI syndrome is far
from homogenous and is not completely understood . Although several
chromosomal abnormalities have been reported in HI the etiology
remains elusive . The pattern of chromosomal aberrations and the
polymorphic nature of this disease have led some to believe that HI
syndrome is a descriptive term rather than a true syndrome .
Most cases are a de novo occurrence although very rare cases of
familial HI following a dominant pattern have been described in the
literature .
P01.309
misdiagnosis in patients with Joubert syndrome
C. Marzocchi1 , K. Ludwig1 , L. Salviati1 , S. Sartori2 , R. Tenconi1 ;
1 2 Servizio di Genetica Clinica, Padova, Italy, Dipartimento di Pediatria, Padova,
Italy.
We report a 18 month-old boy born to a Moroccan non-consanguineous
couple referred to our center for the presence of a Dandy-Walker-
Malformation (DWM) with hydrocephalus and intracranial hypertension,
mental retardation, and cranio-facial dysmorphisms .
About a year after the birth of the proband, a second pregnancy of the
couple was terminated at 20 weeks of gestation after ultrasound detection
of DWM, cleft-lip and -palate and nasal root hypoplasia
The initial diagnosis of DWM in the proband and in the fetus was put
into question . A control MRI performed after placement of a ventriculoperitoneal
shunt at twenty months of age showed the classical “molar
tooth sign”, allowing us to hypothesise the diagnosis of Joubert syndrome
.
Genetic testing is currently being performed .
These results indicate that in the presence of intracranial hypertension
it might be difficult to diagnose the underlying brain malformation.
Therefore the recurrence of DWM, especially if diagnosed only by fetal
brain ultrasound, should take to rule out Joubert syndrome .
P01.310
Novel mutation in the keratin 3 gene in an asymptomatic
family with meesmann corneal dystrophy suggests genotypephenotype
correlation
M. Oldak 1 , J. P. Szaflik 2 , A. Pollak 3 , R. B. Maksym 1 , M. Udziela 2 , R. Płoski 4 , J.
Szaflik 2 ;
1 Department of Histology and Embryology, Center of Biostructure Research,
Medical University of Warsaw, Warsaw, Poland, 2 Department of Ophthalmology,
Medical University of Warsaw, Warsaw, Poland, 3 Institute of Physiology and Pathology
of Hearing, Warsaw, Poland, 4 Department of Medical Genetics, Center
of Biostructure Research, Warsaw Medical University, Warsaw, Poland.
Meesmann corneal dystrophy (MCD, OMIM #122100) is a dominantly
inherited disorder characterized by fragility of the anterior corneal epithelium
and intraepithelial microcysts formation . Although the disease
is generally mild and affected individuals are often asymptomatic, some
suffer from recurrent erosions leading to lacrimation, photophobia and
deterioration in visual acuity . MCD is caused by mutations in keratin
3 (KRT3) or 12 (KRT12) genes encoding cornea-specific cytoskeletal
proteins . Seventeen mutations in KRT12 and only two in KRT3 have
been described so far . In this study we report on a three-generation
Polish family with MCD . Epithelial lesions characteristic for MCD were
visualized with slit-lamp examination and confirmed by in vivo confocal
microscopy . In the proband a direct sequencing of the PCR amplified
coding regions of KRT3 and KRT12 revealed a novel 1493A>T
heterozygous missense mutation in exon 7 of KRT3, which predicts
the substitution of glutamic acid for valine at codon 498 (E498V) . By
a PCR-RFLP test the mutation was demonstrated to segregate with
disease (four affected members, three non-affected) and to be absent
in 100 controls from Polish population indicating that it is not a common
polymorphism . Location of the E498V mutation emphasizes the
functional relevance of the highly conserved boundary motifs at the
C-terminus of the alpha-helical rod domain in KRT3 .
P01.311
A molecular diagnostic service for lacrimoauriculodentodigital
(LADD) syndrome
T. Lester 1 , L. J. Williams 1 , J. N. Berg 2 , D. Goudie 2 , H. Lord 1 , A. O. M. Wilkie 3 ,
A. Seller 1 ;
1 Clinical Molecular Genetics Laboratory, Churchill Hospital, Headington, Oxford,
United Kingdom, 2 Clinical Genetics, Ninewells Hospital, Dundee, United
Kingdom, 3 Weatherall Institute of Molecular Medicine, John Radcliffe Hospital,
Headington, Oxford, United Kingdom.
Lacrimoauriculodentodigital (LADD) syndrome (Levy-Hollister syndrome)
is a rare autosomal dominant condition characterised by multiple
congenital abnormalities mainly affecting the lacrimal glands and
ducts, salivary glands and ducts, ears, teeth and distal limb segments .
In addition there may be mild facial dysmorphism, malformation of the
kidney and respiratory system and abnormal genitalia . The phenotype
of LADD syndrome is highly variable and can range from congenital
renal disease causing death in the neonatal period, to aplasia of the
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