Abstract Lowe (oculocerebrorenal) syndrome is an X-linked recessive disorder characterised by congenital cataract, glaucoma, cognitive developmental delay and renal tubular Fanconi syndrome. In this ...report we present a patient with Lowe syndrome with a tigroid pattern on cranial MRI, which has not been previously reported as an imaging feature of this syndrome.
Wolcott-Rallison syndrome (WRS) is a rare autosomal recessive disorder characterized by early-onset diabetes, spondyloepiphyseal dysplasia, tendency to skeletal fractures secondary to osteopenia, and ...growth retardation. Mutations in the eukaryotic translation initiation factor 2α kinase (EIF2AK3) gene are responsible for this disorder. Here, we describe a boy with neonatal diabetes, diagnosed at 2 months of age, who developed severe growth retardation and a skeletal fracture during the follow-up period. The patient's skeletal X-ray revealed findings of skeletal dysplasia. A clinical diagnosis of WRS was confirmed by the identification of a novel homozygous nonsense mutation (R491X) in exon 9 of the EIF2AK3 gene. The aim of this report is to raise the awareness for Wolcott-Rallison syndrome in cases presenting with isolated neonatal diabetes. This patient demonstrates that the other findings of this syndrome might be obscured by a diagnosis of isolated neonatal diabetes.
We report a newborn girl with multiple congenital anomalies whose chromosomal analysis showed complete trisomy 22. Her phenotype included microcephaly, epicanthus, hypertelorism, micrognathia, cleft ...palate, microtia, and preauricular tag. She died in the 24th post-natal hour. Trisomy 22 was shown by fluorescence in situ hybridization technique and the parental origin of the extra chromosome was found to be maternal by DNA microsatellite marker analysis of chromosome 22. Postmortem examination revealed the presence of atrioseptal defect and stasis in the biliary canals. We believe that this patient will contribute to the literature both by clinical findings and short life span associated with maternal origin of extra chromosome 22.
Multiple pterygium syndrome is characterized by a number of phenotypic features, small stature, webbing of the neck, elbows, and/or knees, and joint contractures. In this report, we present an ...11-year-old boy who had the classical findings of multiple pterygium syndrome, and his chromosomal analysis revealed a 47,XXY karyotype. Interestingly, he did not show any of the main clinical signs of Klinefelter syndrome. This patient appears to be the first reported case in the literature in which a non-mosaic 47,XXY karyotype has been found in a patient with multiple pterygium syndrome. The aim of the present report is to describe a non-classic Klinefelter syndrome associated with multiple pterygium syndrome and to emphasize the importance of karyotype analysis in patients with multiple pterygium syndrome.
Congenital heart disease (CHD) associated with thyroid disease has been reported in Down syndrome (DS). The purpose of this work was to assess abnormalities of the thyroid in relation to the ...frequency and type of CHD on admission among children with DS.
This retrospective study included 187 children with DS between August 1993- December 2005. Karyotype analysis, thyroid function tests and echocardiographic studies were performed in all children with DS. If necessary, hemodynamic study by catheterization was carried out. Thyrotropin releasing hormone (TRH) stimulation test was performed in having elevated thyroid stimulating hormone (TSH) level. Statistical analyses were performed using Chi-square, "t" test for independent samples or Mann-Whitney U test.
It was found that 136 (72.73%) patients with DS had CHD. The age difference at the time of admission was statistically significant for these two groups (p=0.001) in children with /without CHD. There were 12 (11.88%) patients with congenital hypothyroidism and DS, of whom 11 had CHD. There were statistically significant differences in the levels of TSH and total thyroxine (tT4) between congenital and subclinical hypothyroid and euthyroid groups (p=0.001 for TSH and p= 0.001 for tT4). But, there was no significant relationship between having any kind of CHD and levels of TSH and tT4.
Our data suggest that all patients with DS should be evaluated with careful physical and echocardiographic examination on admission. In addition, congenital or subclinical hypothyroidism should also be kept in mind in children with DS and monitored accordingly.
The use of array technology to define chromosome deletions and duplications is bringing us closer to establishing a genotype/phenotype map of genomic copy number alterations. We studied 21 patients ...and five relatives with deletions of the short arm of chromosome 20 using the Illumina HumanHap550 SNP array to: 1) more accurately determine the deletion sizes; 2) identify and compare breakpoints; 3) establish genotype/phenotype correlations; and 4) investigate the use of the HumanHap550 platform for analysis of chromosome deletions. Deletions ranged from 95 kb to 14.62 Mb, and all of the breakpoints were unique. Eleven patients had deletions between 95 kb and 4 Mb and these individuals had normal development, with no anomalies outside of those associated with Alagille syndrome (AGS). The proximal and distal boundaries of these 11 deletions constitute a 5.4-Mb region, and we propose that haploinsufficiency for only 1 of the 12 genes in this region causes phenotypic abnormalities. This defines the JAG1-associated critical region, in which deletions do not confer findings other than those associated with AGS. The other 10 patients had deletions between 3.28 Mb and 14.62 Mb, which extended outside the critical region, and, notably, all of these patients had developmental delay. This group had other findings such as autism, scoliosis, and bifid uvula. We identified 47 additional polymorphic genome-wide copy number variants (>20 SNPs), with 0 to 5 variants called per patient. Deletions of the short arm of chromosome 20 are associated with relatively mild and limited clinical anomalies. The use of SNP arrays provides accurate high-resolution definition of genomic abnormalities. Hum Mutat 0,1-8, 2008.
The acrofacial dysostosis syndromes, which are characterized by malformations of the craniofacial region and limbs, are a clinically heterogeneous group of disorders. Based primarily on the of the ...pattern of limb defects two major groups have emerged: Nager syndrome with predominantly preaxial malformations plus mandibulofacial dysostosis (severe micrognathia and malar hypoplasia) and Miller syndrome with postaxial malformations plus mandibulofacial dysostosis. Among these syndromes, Nager syndrome is a rare condition but the most common form of acrofacial dysostosis. Most cases are sporadic, while autosomal dominant and autosomal recessive inheritance patterns have been reported. Recently, heterozygous mutations in the SF3B4 gene on chromosome 1q12-q21 were found to be responsible for a subset of sporadic and autosomal dominant cases. We present a female infant born to consanguineous parents with craniofacial features resembling Nager syndrome and a unilateral preaxial limb malformation. Mutation analysis of coding exons of SF3B4 did not identify any mutations. This couple also had a deceased child who had similar clinical features. We conclude that, the presence of consanguinity and absence of mutation in SF3B4, provides evidence in support of a recessive form of Nager syndrome.
PDF
