1/41. Familial cryptic translocation between chromosomes 2qter and 8qter: further delineation of the Albright hereditary osteodystrophy-like phenotype.Recently five patients with an Albright hereditary osteodystrophy (AHO)-like phenotype were reported to have a subtelomeric deletion of the long arm of chromosome 2. These patients showed a striking resemblance to a number of patients from a large pedigree known to us for a long time. After molecular confirmation of a subtelomeric deletion in one patient, FISH analysis was used and a cryptic translocation between the long arms of chromosomes 2 and 8, t(2;8)(q37.3;q24.3), was detected. Remarkably, five proven and 10 probable cases with a 2qter deletion were found in the family, but none with an 8qter deletion. This was not explained by increased fetal loss. The major clinical characteristics of terminal 2q deletion are a short, stocky build, round face, sparse hair, deeply set eyes, bulbous nose, thin vermilion border, brachymetaphalangism, seizures, and developmental delay. A specific behavioural phenotype consisting of periods of hyperkinesia and aggression can develop with age. The overall phenotype is sufficiently characteristic to allow clinical recognition. The cytogenetic and molecular studies did not narrow down the common deleted region. Both testing of additional 2q markers and characterisation of other AHO-like patients with 2q37 microdeletions may help to define the candidate gene region.- - - - - - - - - - ranking = 1keywords = behaviour (Clic here for more details about this article) |
2/41. Prenatal detection and mapping of a distal 8p deletion associated with congenital heart disease.We report the prenatal diagnosis, at 18 weeks' gestational age of a del(8)(p23.1-->pter) in a fetus with an atrio-ventricular canal, persistent left superior vena cava and hypoplastic right ventricle detected by sonographic imaging. We further refine the breakpoints associated with this defect using fluorescent in situ hybridization analysis (FISH). Our findings correlate with recent reports of the localization and importance of GATA4 (a zinc finger transcription factor) in cardiac development. Though microcephaly, mental retardation and typical behavioural features are well described in various deletions in 8p, the absence of notable microcephaly in this case raises the possibility for a separate genetic aetiology for some of these features. Indeed, primary autosomal recessive microcephaly (MCPH1) was recently mapped to a nearby region and may be the cause for this frequent observation in some cases of 8p deletions. These observations illustrate the role of FISH in prenatal diagnosis and refinement of chromosomal breakpoints. In addition, mappings of loci significant for cardiac development are presented. Our findings suggest that some features of the 8p deletion syndrome may ultimately be uncoupled from one another, and underscore the need for further study of this region of chromosome 8, in order to achieve adequate information for genetic counselling.- - - - - - - - - - ranking = 1keywords = behaviour (Clic here for more details about this article) |
3/41. Psychiatric inpatients and chromosome deletions within 22q11.2.Velocardiofacial syndrome (VCFS) is a congenital disorder characterised by multiple dysmorphisms, cleft palate, cardiac anomalies, and learning disabilities due to a microdeletion of chromosome 22q11.2. Although VCFS is often associated with psychiatric symptoms, its prevalence among psychiatric patients is unknown. A total of 326 patients admitted in September and October 1997 to a Japanese psychiatric hospital were screened for the clinical features of VCFS. Twelve patients with minor facial dysmorphia were identified; chromosomal analysis with fluorescent in situ hybridisation (FISH) was performed in six patients who, further assessment suggested, were most likely to have VCFS. Chromosome 22q11.2 deletion was identified in a 41 year old woman who had symptoms of schizophrenia but no major dysmorphia, such as cardiovascular anomalies and cleft palate. Her behavioural and neuropsychological profiles were similar to those previously reported in VCFS. She was hemizygous for the FISH probe N25 (GDB locus D22S75) and also for probes N72H9 (D22S181), sc11.1a, C443 (D22S941), sc4.1 (D22S134), sc11.1b, N19B3 (D22S264), N122B5 (D22S934), and N77F7 (D22S939). The size of the deletion was about 3 Mb. Our patient had only some features of VCFS including a square nasal root, hypernasal speech, and hypoparathyroidism. She did, however, have the common larger deletion of type A. This finding suggests that psychiatric symptoms in VCFS can occur without major developmental symptoms such as cardiovascular anomalies and cleft palate. Additional patients with schizophrenia may have subtle features of VCFS which are unrecognised on routine medical examinations.- - - - - - - - - - ranking = 1keywords = behaviour (Clic here for more details about this article) |
4/41. Three young children with smith-magenis syndrome: their distinct, recognisable behavioural phenotype as the most important clinical symptoms.We report on the development and behaviour of three young children with smith-magenis syndrome (SMS), del 17p11.2. The behaviour problems and the psychomotor delay in preschool children with SMS are often more striking than the dysmorphic features and can serve as a useful clue to the diagnosis. We compare the behaviour with reported data. The behaviour problems in the three four year olds include very demanding behaviour, severe temper tantrums, hyperactivity, aggressive behaviour, self injurious behaviour, sleeping problems and stereotypic behaviour. head banging, hand, wrist or finger biting are present. Onychotyllomania is not observed. Insertion of objects in the mouth as well as excessive nose picking is very frequent, although polyembolokoilomania is not present. The so called self hug when excited is present in one child. The behaviour problems and psychomotor delay represent a major management problem for the parents.- - - - - - - - - - ranking = 13keywords = behaviour (Clic here for more details about this article) |
5/41. Familial prader-willi syndrome: case report and a literature review.prader-willi syndrome (PWS) is a neurobehavioural disorder arising through a number of different genetic mechanisms. All involve loss of paternal gene expression from chromosome 15q11q13. Although the majority of cases of PWS are sporadic, precise elucidation of the causative genetic mechanism is essential for accurate genetic counselling as the recurrence risk varies according to the mechanism involved. A pair of siblings affected by PWS is described. Neither demonstrates a microscopically visible deletion in 15q11q13 or maternal disomy. methylation studies at D15S63 and at the SNRPN locus confirm the diagnosis of PWS. Molecular studies reveal biparental inheritance in both siblings with the exception of D15S128 and D15S63 where no paternal contribution is present indicating a deletion of the imprinting centre. family studies indicate that the father of the siblings carries the deletion which, he has inherited from his mother. The recurrence risk for PWS in his offspring is 50%.- - - - - - - - - - ranking = 1keywords = behaviour (Clic here for more details about this article) |
6/41. Otorhinolaringologic manifestation of smith-magenis syndrome.smith-magenis syndrome (SMS) is a multiple congenital anomaly/mental retardation (MCA/MR) syndrome link to a contiguous-gene deletion syndrome, involving chromosome 1 7p 11.2,whose incidence is estimated to be 1:25,000 livebirth. SMS is characterised by a specific physical, behavioural and developmental pattern. The main clinical features consist of a broad flat midface with brachycefaly, broad nasal bridge, brachydactily, speech delay, hoarse deep voice and peripheral neuropathy. Behavioural abnormalities include hypermotility, self-mutilation and sleep disturbance. This report defines the otorhinolaryngological aspects of a new case of SMS, confirmed by cytogenetic-molecular analysis, in a 9 year old girl affected by chronic otitis media, deafness and sinusitis, who presented with typical clinical signs and symptoms.- - - - - - - - - - ranking = 1keywords = behaviour (Clic here for more details about this article) |
7/41. Terminal 6q25.3 deletion and abnormal behaviour.A 10-year-old mentally retarded boy with terminal 6q25 deletion, dysmorphism and striking abnormal behaviour is reported. The main abnormal physical features recorded at different ages consisted of hydrocephalus, axial hypotonia, absence of spontaneous prehension, long face, synophris, hypertelorism with epicanthic folds, internal alternating strabismus, retinal abnormalities with macular degeneration, beaked nose, long philtrum, high-arched palate, lumbar spina bifida, right paravertebral dimple at the upper sacral region, prominent coccyx, broad thumbs and great toes, fetal pads and cryptorchidism. The special behavioural difficulties were made of restlessness, hyperactivity, obsessive compulsive reactions with a self-injurious tendency and episodes of apparently voluntary vomiting crisis concomitant with stress periods. A review of the available literature strongly suggests that individuals with small chromosomal deletions are at high risk of developing behavioural problems.- - - - - - - - - - ranking = 7keywords = behaviour (Clic here for more details about this article) |
8/41. Chromosome 22q11 deletion syndrome (CATCH 22): neuropsychiatric and neuropsychological aspects.Twenty children and young adults (age range 5 to 33 years, 12 females and eight males) with genetically confirmed 22q11 deletion syndrome (CATCH 22: Cardiac anomaly, Anomalous face, Thymus hypoplasia/aplasia, cleft palate, and Hypocalcaemia), recruited from a large ongoing study, were given comprehensive assessments with a view to determining the pattern of neuropsychiatric and neuropsychological deficits thought to be part of the syndrome in many cases. IQ ranged between 46 and 100 with a mean score of 70. Half the group had an IQ <70. In 13 individuals, attention-deficit-hyperactivity disorder (ADHD), mainly inattentive or combined type in most cases, and/or autism spectrum problems were diagnosed. Many participants, even among those who had an IQ within the normal range and had neither ADHD nor autistic spectrum problems, showed a characteristic and pronounced behavioural profile with low mental energy, initiation difficulties, deficits in sustained attention, and social interaction (often augmented by limited facial expression and communication and speech problems).- - - - - - - - - - ranking = 1keywords = behaviour (Clic here for more details about this article) |
9/41. Polymicrogyria in chromosome 22q11 deletion syndrome.central nervous system (CNS) dysfunction is a cardinal feature in 22q11 deletion. The underlying CNS abnormalities remain, however, unknown. We report unilateral hemispheric polymicrogyria in a child with 22q11 deletion presenting with hemiplegia and cognitive and behavioural disorders. This observation widens the spectrum of brain malformations associated with this genetic defect. It further suggests a relationship between the 22q11 deletion and disorders of cerebral gyration. It would therefore be interesting to look for neuronal migration disorders in patients with 22q11 deletion presenting neurological signs, and on the other hand to screen for 22q11 deletion in patients with isolated neuronal migration disorders.- - - - - - - - - - ranking = 1keywords = behaviour (Clic here for more details about this article) |
10/41. A familial cryptic subtelomeric deletion 12p with variable phenotypic effect.A 15-year-old-boy and his mother, both carrying a cryptic deletion within 12p13.33, are described. The proband has a mild phenotype with moderate mental retardation and severe behavioural problems. The mother had some learning difficulties at school. Conventional GTL-banded high-resolution chromosome analysis showed normal karyotypes. Subsequent analysis by fluorescence in situ hybridization using a set of probes specific for the subtelomeric regions of all chromosomes, plus a series of probes at 12p13.33 extending from the 12p telomere, showed that both mother and son carry a 1.65 Mb terminal deletion in this region. There are 10 predicted genes within the deleted region. The unanticipated familial nature of the deletion emphasizes the value of family studies in all cases with subtelomeric abnormalities. It also demonstrates the difficulty in making a clinical diagnosis of individuals with this deletion. To the best of the present authors' knowledge, the proband and his mother are the first patients described with a submicroscopic deletion at 12p13.33.- - - - - - - - - - ranking = 1keywords = behaviour (Clic here for more details about this article) |
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