2008 Barcelona - European Society of Human Genetics

Cytogenetics
P02.078
mental Retardation, Epilepsy and Venous thromboembolic
Disease in a Patient with a 48,XXYY Karyotype
M. Obón 1 , M. Alsius 1 , A. Molins 2 , I. Recas 3 , A. Bustins 4 , C. Pascual Mostaza 1 ;
1 Department of Genetics and Molecular Biology. Laboratori Clínic ICS Girona.
Hospital U. de Girona Dr. J. Trueta, Girona, Spain, 2 Epilepsy Unit. Hospital U.
de Girona Dr. J. Trueta, Girona, Spain, 3 Department of Endocrinology. Hospital
U. de Girona Dr. J. Trueta, Girona, Spain, 4 Department of Haematology, ICO,
Girona, Spain.
48,XXYY syndrome was initially considered a variant of Klinefelter
syndrome . Nowadays, it is accepted as a distinct clinical and genetic
entity .
We report the case of a 27-year-old man diagnosed with cryptogenic
partial epilepsy and action tremor in both hands unresponsive to betablockers
. Due to speech and language delays and mild mental retardation
a karyotype analysis was performed, which indicated that all cells
were 48,XXYY .
The patient was born without neonatal complications to a healthy
couple with an unremarkable family history . On beginning school,
language delay and learning disabilities were detected . Language
therapy helped him to develop complex language skills . He was diagnosed
with asthma when he was 5 years old . At 19, idiopathic deep
vein thrombosis developed in his left leg which required 8 months of
oral anticoagulant therapy .
Phenotypically tall with eunuchoid habitus, gynecomastia . Craniofacial
dimorphism described as a “pugilistic” facial appearance . Hypergonadotropic
hypogonadism, small testes and normal penis . Leg ulcers
and varicosities .
Behavioural features consist of immaturity, passivity and temper outbursts
but a friendly and cooperative nature . High overall scores on
adaptive scales in daily living, socialization and communication . His
parents have exposed their son to a variety of activities and interests
and provided consistent intervention and support when needed .
The addition of more than one extra X and Y chromosome to a normal
male karyotype rarely occurs and it has its own distinctive physical
and behavioural profile. There are significant variations within each
polysomy X and Y group and hence no generalised prognosis can be
made .
P02.079
A 7-year-old boy with profound mental retardation, peculiar face,
tracheo-esophageal fistula and bilateral sensorineural hearing
loss caused by interstitial deletion 17q22-q23.3
H. Puusepp 1,2 , O. Zilina 2 , K. Männik 2 , S. Parkel 2 , R. Teek 3,4 , K. Kuuse 3 , A. Kurg 2 ,
K. Õunap 3,1 ;
1 Department of Pediatrics, University of Tartu, Tartu, Estonia, 2 Department of
Biotechnology, Institute of Molecular and Cell Biology, Tartu, Estonia, 3 Department
of Genetics, Tartu University Hospital, Tartu, Estonia, 4 Department of
Oto-Rhino-Laryngology, University of Tartu, Tartu, Estonia.
Microdeletions of the long arm of chromosome 17 are rare . By our
knowledge, only few cases have been reported involving deletions of
chromosome 17 in region q22-q24. Common findings are microcephaly,
abnormal face, anomalies of the hands, growth retardation and
severe developmental delay .
Here we present a 7-year-old boy, who was born normally at term
with normal birth weight 3480g and length 50cm, and microcephaly
(-2 SD). Soon after the birth tracheo-esophageal fistula was diagnosed
and therefore operated . At the age 7 years clinical evaluation
revealed failure to thrive (-2 .5 SD), microcephaly (-5 SD), profound
mental retardation, stereotypic movements, peculiar facies - high
forehead, palpebral fissures slant up, blepharophimosis, ptosis, hypertelorism,
epicanthal folds, strabismus, broad nasal tip, high palate,
low set and dysplastic ears, and preauricular pits . Additionally he had
bilateral severe sensorineural hearing loss, kyphosis, scoliosis, spina
bifida occulta, contractures of joints, tall fingers, partial syndactyly of
II-V fingers and II-V toes, sandle gap of toes, micropenis, cryptorchid
testes, and mild hirsutism . During pediatric evaluations psoriasis vulgaris,
asthma, celiac disease, iron deficient anemia and mild hypothyreosis
was diagnosed. We have applied Infinium-2 genotyping assay
with Human370CNV-Duo BeadChips (Illumina Inc .), which showed a
5 .9 Mb deletion of chromosome region 17q22-q23 .3 with a breakpoint
between 48,287,327 and 54,245,662bp. The aberration was confirmed
by real-time PCR analysis .
Regarding to our patients findings, we suggest that a locus for sensorineural
hearing loss and a locus for tracheo-esophageal fistula may
be located in the region of 17q22-q23 .3 . This work was supported by
GARLA 6808 .
P02.080
An unusual case of ring chromosome 14 with Epilepsy and
developmental delay
A. Nucaro 1 , M. Falchi 2 , M. Meloni 2 , R. Rossino 3 , T. Pisano 2 , C. Cianchetti 2 , D.
Pruna 4 ;
1 Istituto di Neurogenetica e Neurofarmacologia, Monserrato( Cagliari), Italy, 2 Dipartimento
di Neuroscienze, Neuropsichiatria Infantile, University, Cagliari, Italy,
3 Dipartimento di Scienze Pediatriche e Medicina Clinica, University, Cagliari,
Italy, 4 Dipartimento di Neuroscienze, Neuropsichiatria Infantile, Cagliari, Italy.
We present a 10-year-old boy, born to young , healthy and non-consanguineous
parents, with an unusual ring chromosome 14 associated
to epilepsy and mental retardation. At the age of five months he
had seizures confirmed by EEG as epilepsy. Seizures were resistant
to common antiepileptic drugs . He also had microcephaly, hypertelorism
, microretrognathia , large auricula , micropenis , hypotonia .
Cytogenetic investigation and FISH studies of the proband revealed
an unusual chromosomal mosaicism 46,XY,r(14)(p13q32)/46,XY,dup
r(14),ish (14wcp+) .Over 50 examined metaphases, 48 had a ring chromosome
14 and only 2 had a duplicated ring chromosome 14(4%) .
The abnormality r(14) is a rare cytogenetic disorder with characteristic
features and episode of uncontrolled seizures . To the best of our
knowledge, this is the first report describing a ring chromosome 14 mosaicism
associated to a duplicated ring chromosome 14 . Array-CGH
analysis will be performed to detect cryptic submicroscopic rearrangements
in the ring formation . We carried out this study to search for the
cause of the seizures in our patient . Several hypotheses could be explain
these, such as mitotic instability of ring chromosome or telomere
position effect in ring chromosomes . We could also hypothesize that
14p telomere silences nearby genes on the q arm and close dependent
genes involved in the seizures .
P02.081
Partial trisomy 15q11-13 as a cause of acute onset intractable
epilepsy
M. Michelson1,2 , A. Eden3,2 , C. Vinkler1,2 , M. Yanoov- Sharav1,2 , T. Lerman-Sagie3,2
, D. Lev1,2 ;
1 2 Institute of Medical Genetics, Holon, Israel, Metabolic Neurogenetic Clinic,
Holon, Israel, 3Pediatric Neurology Unit, Holon, Israel.
Various rearrangements involve the proximal long arm of chromosome
15, including deletions, duplications, translocations, inversions and
supernumerary marker chromosome with the inverted duplication of
proximal chromosome 15 .
The large marker 15, that contains the Prader-Willi syndrome (PWS)/
Angelman syndrome (AS) chromosome region, is usually associated
with an abnormal phenotype of moderate to severe mental retardation,
seizures, poor motor coordination, early-onset central hypotonia, autism
and autistic-like behavior and mild dysmorphic features . Positive
genetic linkage with 15q region has also been found in patients with
schizophrenia . Most of the reported cases are of maternal origin .
We report here an eight year-old girl with normal intelligence who developed
severe intractable seizures at age seven years . Family history
was significant for a mother with episodes of acute psychosis.
The patient’s leukocyte karyotype revealed 47XX+m . Her mother’s
karyotype looked identical .
Array comparative Genomic Hybridization (A-CGH) identified a gain
of 13 BAC clones from 15q11 .2 through 15q13 .1, which was then confirmed
by Fluorescent In-Situ Hybridization (FISH). This duplicated region
is approximately 5 .6 Mb in size and contains the SNRPN/UBE3A
loci .
Although severe epilepsy has been described in association with rearrangements
of the proximal long arm of chromosome 15, all reported
cases had mental retardation .
This is the first report of a patient with intractable epilepsy and nearly
normal intelligence, associated with partial trisomy of 15q11-13 . She
inherited this marker chromosome from her mother, who has psychiatric
illness .
We suggest that this region should be tested by FISH in cases with
intractable epilepsy, with or without developmental delay/MR .