1/55. Mutchinick syndrome in a Japanese girl.We report on a 7-year-old Japanese girl with Mutchinick syndrome, a rare congenital malformation syndrome described in a pair of Argentinean sisters and a pair of German brothers; both originating from the same geographic region in the former East prussia. The girl we describe had most of the clinical manifestations of the syndrome, including growth and developmental retardation, and craniofacial anomalies with microcephaly, hypertelorism, a broad straight nose, low-set malformed ears, and a wide, tented mouth. She also had the following hitherto undescribed manifestations: ventricular septal defect, palmoplantar hyperkeratosis, bilateral partial soft-tissue syndactyly of second and third toes, and megaloureters. The occurrence of the syndrome in a Japanese girl indicates that the syndrome is not restricted to the descendants of individuals from a confined region in northeastern europe.- - - - - - - - - - ranking = 1keywords = microcephaly (Clic here for more details about this article) |
2/55. 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 = 1keywords = microcephaly (Clic here for more details about this article) |
3/55. Bartsocas-Papas syndrome with fusion of the lips and posterior fusion defects of the thoracic vertebrae.Bartsocas-Papas syndrome is a rare popliteal pterygial syndrome with multiple anomalies including microcephaly, facial clefts, filiform bands, ankyloblepharon, syndactyly, and other ectodermal anomalies. Affected infants usually die perinatally. The authors present an 8-month-old female infant with manifestations of this syndrome and some additional traits including fusion of the lips, intraoral filiform bands, alopecia totalis, and posterior fusion failure of the vertebrae. The fused lips were opened by incising the fibrotic bands closing her mouth. Details of this patient and a brief review of the literature is presented.- - - - - - - - - - ranking = 1keywords = microcephaly (Clic here for more details about this article) |
4/55. Two female siblings with a previously unreported MCA/MR syndrome: pre- and postnatal growth retardation, iris colobomata, spasticity, facial dysmorphism and dilated ventricles.We report two siblings from non consanguineous parents with a similar MCA/MR syndrome: Pre- and postnatal growth retardation, microcephaly, mental retardation, iris colobomata, facial dysmorphism, spasticity, dilated ventricles and abnormal immunoglobulin levels. review of published reports and the use of the london Dysmorphology database suggests that these siblings may present a new syndrome.- - - - - - - - - - ranking = 1keywords = microcephaly (Clic here for more details about this article) |
5/55. 46, XY, del (3) (pter-->p25) syndrome: further delineation of the clinical phenotype.A boy with monosomy for the distal part of the short arm of chromosome 3 is described. The clinical features this patient has in common with the previously reported cases include pre- and post-natal growth delay, microcephaly, craniofacial dysmorphism and mental retardation. In addition, minor abnormalities not previously reported were observed, such as snapping thumbs, dorsiflected big toes, connecting anterior and posterior fontanelles at birth, nasolacrimal duct stenosis and double urethral meatus.Conclusion These five new clinical findings may help in further delineation of the syndrome and allow its early recognition. A complete revision of clinical findings published in literature is reported.- - - - - - - - - - ranking = 1keywords = microcephaly (Clic here for more details about this article) |
6/55. Autozygosity mapping of a seckel syndrome locus to chromosome 3q22. 1-q24.Seckel syndrome (MIM 210600) is an autosomal recessive disorder of low birth weight, severe microcephaly, and dysmorphic facial appearance with receding forehead, prominent nose, and micrognathia. We have performed a genomic screen in two consanguineous families of Pakistani origin and found that the disorder segregates with markers between loci D3S1316 and D3S3710, which map to chromosome 3q22.1-q24. Analysis using HOMOZ/MAPMAKER gave a maximum lod score of 8.72. All five affected individuals were homozygous for the same allele, for two adjacent polymorphic markers within the region segregating with the disease, narrowing the region to 12 cM.- - - - - - - - - - ranking = 1keywords = microcephaly (Clic here for more details about this article) |
7/55. Manifestations in four males with and an obligate carrier of the Lenz microphthalmia syndrome.Lenz microphthalmia syndrome is a rare X-linked recessive condition first described by Lenz in 1955 and comprises of anophthalmia, microcephaly, mental retardation, external ear, digital, cardiac, skeletal, and urogenital anomalies. We present three brothers (ages 15 years, 9 years, and 18 months) and a maternal uncle (age 27 years) with congenital anophthalmia, delayed motor development, hypotonia, and moderate to severe mental retardation. They also have abnormally modeled ears, high-arched palate, pectus excavatum, finger and toe syndactyly, clinodactyly, fetal pads, scoliosis, cardiac, and renal abnormalities. An obligate carrier had abnormally modeled ears and syndactyly of the 2nd to 3rd toes bilaterally. Linkage and haplotype analysis in this family indicates that the gene is located in a 17.65-cM region on chromosome region Xq27-Xq28.- - - - - - - - - - ranking = 1keywords = microcephaly (Clic here for more details about this article) |
8/55. Evidence for the "midline" hypothesis in associated defects of laterality formation and multiple midline anomalies.A male infant was liveborn at 38 weeks of gestation to a G4P1AB2, 22-year-old, mother. polyhydramnios and multiple congenital anomalies were noted by ultrasonography; the infant died 5 min after birth. At autopsy, the infant had multiple defects of blastogenesis including midline anomalies with asplenia and abnormalities of laterality formation. The laterality defects were unusual in that they combined asplenia with hypoplastic, symmetrically unilobate lungs and bilateral hyparterial bronchi more consistent with polysplenia, abdominal situs inversus with midline stomach, symmetric liver, and left gallbladder. No intracardiac abnormalities were present, but there was azygous continuation of the inferior vena cava. Additional multiple midline defects included bronchoesophageal fistula, duodenal atresia, absence of posterior leaf of diaphragm; horseshoe adrenal gland; microcephaly; Dandy-Walker anomaly with agenesis of cerebellar vermis and occipital encephalocele; holoprosencephaly with orbital encephalocele, midline defect of the orbital plate of the skull, bilateral anophthalmia, double proboscis with bilateral choanal atresia, midline upper lip and palatal cleft; single-lobed thyroid; hypoplastic external genitalia with midline cleft of scrotum, long tapering fingers, and defects of the cranium at the sites of orbital and occipital encephaloceles. Defects of laterality frequently are associated with other complex midline anomalies, which both result from a disturbance of pattern formation during blastogenesis, i.e., the induction of the progenitor fields. The latter are the result of the establishment of upstream expression domains of growth and transcription factors and other morphogens. Many of these and other genetic systems, expressed asymmetrically around the midline, are responsible for laterality formation and are the result of upstream and subsequent downstream gene expression cascades through the expression of genes such as HOX genes; bFGF; transforming growth factor beta/activins/BMP4; WNT-1,8; and SHH.- - - - - - - - - - ranking = 1keywords = microcephaly (Clic here for more details about this article) |
9/55. Prenatal sonographic diagnosis of Neu-Laxova syndrome.We report the sonographic diagnosis of Neu-Laxova syndrome in a fetus at 27 weeks' menstrual age. The parents were first cousins. Sonography revealed microcephaly, a sloping forehead, exophthalmos, a small thorax and abdomen, hypoplastic lungs, syndactyly, hyperextended knees, polyhydramnios, a small placenta, and intrauterine growth restriction. The long bones were normal. The calvaria was hyperechoic and associated with shadowing, obscuring any intracranial abnormalities. This sonographic finding was presumed to represent calvarial calcification, not previously described with this syndrome. We believe that Neu-Laxova syndrome can be reliably diagnosed prenatally by demonstrating the sonographic features described, although other conditions with similar sonographic features need to be considered in the differential diagnosis.- - - - - - - - - - ranking = 1keywords = microcephaly (Clic here for more details about this article) |
10/55. neuroblastoma in a dysmorphic girl with a partial duplication of 2p caused by an unbalanced translocation.A 1-year-old female child with multiple dysmorphic features including microcephaly, hypertelorism, a short philtrum, low set ears, a narrow high arched palate, micrognathia and growth retardation was found to have a de novo chromosome abnormality including a partial duplication of the short arm of chromosome 2 and a partial deletion of the long arm of chromosome 17. The clinical features of the case shared many similarities to previous reports of trisomy 2p. Three years later, ecchymotic spots appeared around the left ocular region. Further clinical and pathological examination confirmed the diagnosis of a neuroblastoma. This is the first case of an unbalanced translocation, 46, XX, der (17), t (2; 17) (p23; q25), showing the development of a neuroblastoma in addition to the dysmorphic features. We suggest that trisomy 2p including the N-myc proto-oncogene may have predisposed the patient to the development of a neuroblastoma.- - - - - - - - - - ranking = 1keywords = microcephaly (Clic here for more details about this article) |
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