1/61. Delineation of two distinct 6p deletion syndromes.Deletions of the short arm of chromosome 6 are relatively rare, the main features being developmental delay, craniofacial malformations, hypotonia, and defects of the heart and kidney, with hydrocephalus and eye abnormalities occurring in some instances. We present the molecular cytogenetic investigation of six cases with 6p deletions and two cases with unbalanced translocations resulting in monosomy of the distal part of 6p. The breakpoints of the deletions have been determined accurately by using 55 well-mapped probes and fluorescence in situ hybridization (FISH). The cases can be grouped into two distinct categories: interstitial deletions within the 6p22-p24 segment and terminal deletions within the 6p24-pter segment. Characteristics correlating with specific regions are: short neck, clinodactyly or syndactyly, brain, heart and kidney defects with deletions within 6p23-p24; and corneal opacities/iris coloboma/Rieger anomaly, hypertelorism and deafness with deletions of 6p25. The two cases with unbalanced translocations presented with a Larsen-like syndrome including some characteristics of the 6p deletion syndrome, which can be explained by the deletion of 6p25. Such investigation of cytogenetic abnormalities of 6p using FISH techniques and a defined set of probes will allow a direct comparison of reported cases and enable more accurate diagnosis as well as prognosis in patients with 6p deletions.- - - - - - - - - - ranking = 1keywords = brain (Clic here for more details about this article) |
2/61. Fetal craniofacial structure and intracranial morphology in a case of Apert syndrome.Apert syndrome is characterized by craniosynostosis, midfacial hypoplasia and bilateral syndactyly. We document in detail the intrauterine natural history of Apert syndrome by serial sonographic examination. Ultrasound examination of a 19-week fetus revealed an abnormal appearance of the skull. The subsequent examination including transvaginal brain scanning demonstrated a deformed occipital part of the cerebrum and lateral ventricles, frontal bossing, a low nasal bridge and an abnormal appearance of the fetal hands and feet. The distortion of the fetal profile became progressively worse with advancing gestation. Towards the end of pregnancy, anterior prominence of the cerebrum, ventricles and corpus callosum was demonstrated and mild non-progressive ventriculomegaly was seen. The female 3152-g newborn with the typical facial appearance of Apert syndrome, bilateral syndactyly of the fingers and toes and isolated cleft palate was delivered at 37 weeks. Postnatal three-dimensional computed tomography scan demonstrated the fusion of the coronal suture and a wide mid-line calvarial defect, and cranial magnetic resonance imaging confirmed the prenatal sonographic findings. Although the karyotype was normal, genomic dna analysis of the fibroblast growth factor receptor 2 revealed Ser252Trp, which is specified in the mutational basis of Apert syndrome. The time course of the prenatal findings in this case may help increase understanding of the intrauterine natural history of Apert syndrome.- - - - - - - - - - ranking = 1keywords = brain (Clic here for more details about this article) |
3/61. The smith-magenis syndrome: a new case with infant spasms.The smith-magenis syndrome (SMS) is characterized by congenital anomalies, mental retardation and the interstitial deletion of the 17p. 11.2 chromosome. The subjects affected by this syndrome show cranio-facial dysmorphias, brachycephalia, skeletal, ocular, cardiac, genitourinary and otolaryngological anomalies. The central nervous system is affected and this may be shown by psychomotor retardation, intellective deficit, electroencephalographic alterations (reduced/missing REM phase); the neuroradiological tests detect megacisterna magna, cerebellar hypoplasia, cortical dysplasia, ventricular asymmetry. Behavioural troubles are frequent and, among them, self-aggressive conducts (tearing out the nails). The syndrome is associated with the interstitial deletion of the 17p. 11.2 chromosome. The diagnosis can be made in the pre-natal period and a mosaic situation is possible. Even though the cases of SMS reported in the literature allow defining a characteristic phenotype, studies have been carried out to quantify the deletion of the chromosome 17 in order to identify the chromosomic tract which is responsible for the phenotypical induction. The deletion can either appear de novo or come from one of the parents. In addition, these subjects can show peripheral neuropathy, missing or reduced deep tendon reflexes and (rarely) epileptic crises. However, by reviewing the literature, no descriptions of patients affected by infant spasms are pointed out. This report refers to a new case of smith-magenis syndrome in a nine-month-old girl with spasms in extension.- - - - - - - - - - ranking = 3.750579624616keywords = central nervous system, nervous system (Clic here for more details about this article) |
4/61. Mutations in the homeodomain of the human SIX3 gene cause holoprosencephaly.holoprosencephaly (HPE) is a common, severe malformation of the brain that involves separation of the central nervous system into left and right halves. Mild HPE can consist of signs such as a single central incisor, hypotelorism, microcephaly, or other craniofacial findings that can be present with or without associated brain malformations. The aetiology of HPE is extremely heterogeneous, with the proposed participation of a minimum of 12 HPE-associated genetic loci as well as the causal involvement of specific teratogens acting at the earliest stages of neurulation. The HPE2 locus was recently characterized as a 1-Mb interval on human chromosome 2p21 that contained a gene associated with HPE. A minimal critical region was defined by a set of six overlapping deletions and three clustered translocations in HPE patients. We describe here the isolation and characterization of the human homeobox-containing SIX3 gene from the HPE2 minimal critical region (MCR). We show that at least 2 of the HPE-associated translocation breakpoints in 2p21 are less than 200 kb from the 5' end of SIX3. Mutational analysis has identified four different mutations in the homeodomain of SIX3 that are predicted to interfere with transcriptional activation and are associated with HPE. We propose that SIX3 is the HPE2 gene, essential for the development of the anterior neural plate and eye in humans.- - - - - - - - - - ranking = 5.750579624616keywords = central nervous system, brain, nervous system (Clic here for more details about this article) |
5/61. X linked severe mental retardation, craniofacial dysmorphology, epilepsy, ophthalmoplegia, and cerebellar atrophy in a large South African kindred is localised to Xq24-q27.To date over 150 X linked mental retardation (XLMR) conditions have been documented. We describe a five generation South African family with XLMR, comprising 16 affected males and 10 carrier females. The clinical features common to the 16 males included profound mental retardation (100%), mutism despite apparently normal hearing (100%), grand mal epilepsy (87.5%), and limited life expectancy (68.8%). Of the four affected males examined, all had mild craniofacial dysmorphology and three were noted to have bilateral ophthalmoplegia and truncal ataxia. Three of 10 obligate female carriers had mild mental retardation. Cerebellar and brain stem atrophy was shown by cranial imaging and postmortem examination. Linkage analysis shows the gene to be located between markers DXS424 (Xq24) and DXS548 (Xq27.3), with a maximum two point lod score of 3.10.- - - - - - - - - - ranking = 1keywords = brain (Clic here for more details about this article) |
6/61. proteus syndrome: craniofacial and cerebral MRI.The proteus syndrome is a rare hamartoneoplastic syndrome that may affect the brain, skull, and extracranial head and neck. We present a case with severe, characteristic findings. Brain abnormalities are not common in proteus syndrome; when present, hemimegalencephaly and migrational disorders are typically seen, commonly with an associated seizure disorder. Maxillary and mandibular dysmorphism may occur, including unilateral condylar hyperplasia. Subcutaneous fatty, fibrous, lymphangiomatous masses commonly seen in this syndrome may involve the neck and face, leading to disfigurement and potential airway compromise.- - - - - - - - - - ranking = 1keywords = brain (Clic here for more details about this article) |
7/61. Knobloch syndrome involving midline scalp defect of the frontal region.We report on a 4-year-old boy with Knobloch syndrome. He has vitreoretinal degeneration, high myopia, cataract, telecanthus, hypertelorism, and a high-arched palate. He also has a defect of the anterior midline scalp with involvement of the frontal bone as documented by a computed tomography (CT) scan. The brain was normal on CT scan and magnetic resonance imaging. We present a review of the 23 published cases with this syndrome. Our patient illustrates the importance of investigating for underlying ocular and central nervous system pathology whenever midline scalp defects are present.- - - - - - - - - - ranking = 4.750579624616keywords = central nervous system, brain, nervous system (Clic here for more details about this article) |
8/61. Interstitial tandem duplication of 6p: a case with partial trisomy (6)(p12p21.3).A de novo interstitial tandem duplication of 6p12p21.3 was observed in a 7-month-old boy with growth retardation, psychomotor delay and craniofacial, brain, limb, and genital anomalies. Fluorescent in situ hybridization using a chromosome 6 paint probe demonstrated that the extra material belonged to chromosome 6. Although it has been suggested that 6p25 is the critical band involved in the expression of the phenotype of 6p duplication, comparison of the clinical findings of this case with those from the literature cases showed strong similarities.- - - - - - - - - - ranking = 1keywords = brain (Clic here for more details about this article) |
9/61. Audiovestibular phenotype associated with a COL11A1 mutation in Marshall syndrome.BACKGROUND: Marshall syndrome is a dominant disorder characterized by craniofacial and skeletal abnormalities, sensorineural hearing loss, myopia, and cataracts, and is associated with splicing mutations in COL11A1. OBJECTIVE: To determine the auditory and vestibular phenotypes associated with a COL11A1 splicing. DESIGN: Clinical otolaryngologic, audiologic, vestibular, and radiologic evaluations of the auditory and vestibular systems. SUBJECTS: Three affected individuals from a family cosegregating Marshall syndrome and a COL11A1 splice site mutation. RESULTS: The study subjects have progressive sensorineural hearing loss that is predominantly cochlear in origin and asymptomatic dysfunction of the central and peripheral vestibular systems. Computed tomography detected no malformations of temporal bone structures. CONCLUSIONS: The observed auditory and vestibular abnormalities are not caused by defective morphogenesis of the osseous labyrinth, but by more direct effects of the COL11A1 mutation on the membranous labyrinth and the central nervous system. The onset and degree of hearing loss associated with COL11A1 mutations are useful clinical features to differentiate Marshall syndrome from the phenotypically similar Stickler syndrome.- - - - - - - - - - ranking = 3.750579624616keywords = central nervous system, nervous system (Clic here for more details about this article) |
10/61. Marden-Walker syndrome: case report, nosologic discussion and aspects of counseling.The Marden-Walker syndrome is characterized by a mask-like face with blepharophimosis, micrognathia, cleft or high-arched palate, low-set ears, congenital joint contractures, decreased muscular mass, failure to thrive and psychomotor retardation. We report a boy with a phenotype mostly resembling the condition named Marden-Walker syndrome, with many of the criteria proposed for diagnosing this particular phenotype. In addition he had hypoplastic corpus callosum, cerebellar vermis hypoplasia, enlarged cisterna magna and vertebral abnormalities. During pregnancy there were reduced fetal movements. In the present patient the fetal hypokinesia sequence, due to central nervous system malformation, is most compatible with the diagnosis of Marden-Walker syndrome. The etiology is probably heterogeneous, but the possibility of autosomal recessive inheritance should be considered in genetic counseling.- - - - - - - - - - ranking = 3.750579624616keywords = central nervous system, nervous system (Clic here for more details about this article) |
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