Sotos Syndrome
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What is Sotos syndrome?Sotos syndrome is a disorder characterized by a distinctive facial appearance, overgrowth in childhood, and learning disabilities or delayed development. Characteristic facial features include a long, narrow face; a high forehead; flushed (reddened) cheeks; and a small, pointed chin. In addition, the outside corners of the eyes may point downward (down-slanting palpebral fissures). This facial appearance is most notable in early childhood. Affected infants and children tend to grow quickly; they are significantly taller than their siblings and peers and have an unusually large head. Adult height is usually in the normal range, however. People with Sotos syndrome often have intellectual impairment, and most also have behavioral problems. Frequent behavioral issues include attention deficit hyperactivity disorder (ADHD), phobias, obsessions and compulsions, tantrums, and impulsive behaviors. Problems with speech and language are also common. Affected individuals often have problems with sound production, stuttering, and a monotone voice. Additionally, weak muscle tone (hypotonia) may delay other aspects of early development, particularly motor skills such as sitting and crawling. Other signs and symptoms of Sotos syndrome can include an abnormal side-to-side curvature of the spine (scoliosis), seizures, heart or kidney defects, hearing loss, and problems with vision. Some infants with this disorder experience yellowing of the skin and whites of the eyes (jaundice) and poor feeding. A few people with Sotos syndrome have developed cancer, most often in childhood, but no single form of cancer has been associated with this condition. It remains uncertain whether Sotos syndrome increases the risk of specific types of cancer. If people with this disorder have any increased cancer risk, their risk is only slightly greater than that of the general population. How common is Sotos syndrome?Sotos syndrome is reported to occur in 1 in 10,000 to 14,000 newborns. Many cases of this disorder are not diagnosed, however, so the true incidence may be closer to 1 in 5,000. What genes are related to Sotos syndrome?Mutations in the NSD1 gene cause Sotos syndrome. The NSD1 gene provides instructions for making a protein that is involved in normal growth and development. The function of this protein is unknown, however. In the Japanese population, the most common genetic change leading to Sotos syndrome deletes genetic material from the region of chromosome 5 containing the NSD1 gene. In other populations, small mutations within the NSD1 gene occur more frequently. Genetic changes involving the NSD1 gene prevent one copy of the gene from producing any functional protein. It is unclear how a reduced amount of this protein during development leads to learning disabilities, overgrowth, and the other features of Sotos syndrome. How do people inherit Sotos syndrome?About 95 percent of Sotos syndrome cases occur in people with no history of the disorder in their family. Most of these cases result from new mutations involving the NSD1 gene. A few families have been described with more than one affected family member. These cases helped researchers determine that Sotos syndrome has an autosomal dominant pattern of inheritance. Autosomal dominant inheritance means one copy of the altered gene in each cell is sufficient to cause the disorder.
Source: National Institutes of Health
Study data from University Hospital, Department of Clinical Genetics update understanding of sotos syndrome genetics
2007 NOV 21 -- Current study results from the report, 'Leukocyte cDNA analysis of NSD1 derived from confirmed Sotos syndrome patients,' have been published. According to a study from Copenhagen, Denmark, "Haploinsufficiency of the NSD1 gene leads to Sotos syndrome (Sos), which is characterised by excessive growth, especially during childhood, distinct craniofacial features and variable degree of mental impairment. A wide spectrum of NSD1 mutations have been described in Sos patients, ranging from more than 100 different single nucleotide changes, to partial gene deletions, and to microdeletions of various sizes comprising the entire NSD1 locus To investigate the NSD1 cDNA sequence in genetically confirmed Sos patients harbouring truncating and missense mutations Total RNA was isolated from a 250 mcl standard EDTA blood sample from nine genetically verified Sos patients, and subsequent reverse-transcribed into cDNA followed by PCR and direct sequencing of specific NSD1 cDNA sequences All nine mutations, including missense, nonsense and whole exon deletions, previously identified in genomic DNA, could confidently be detected in cDNA." "Several NSD1 transcript splice variants were detected Despite the fact that Sos is caused by haploinsufficiency, NSD1 transcripts containing nonsense and frame shift mutations can be detected in leukocyte-derived cDNA. The possibility therefore exists that certain NSD1 mutations are expressed and contribute to the phenotypic variability of Sos," wrote M. Duno and colleagues, University Hospital, Department of Clinical Genetics. The researchers concluded: "NSD1 cDNA analysis is likely to enhance mutation detection in Sos patients." Duno and colleagues published their study in Annals of Human Genetics (Leukocyte cDNA analysis of NSD1 derived from confirmed Sotos syndrome patients. Annals of Human Genetics, 2007;71(Pt 6):713-8). For more information, contact M. Duno, Rigshospitalet 4062, Dept. of Clinical Genetics, University Hospital Copenhagen, Blegdamsvej 9, DK-2100 Copenhagen, Denmark. Publisher contact information for the journal Annals of Human Genetics is: Blackwell Publishing Ltd., 9600 Garsington Rd., Oxford OX4 2DG, Oxon, England. Keywords: Denmark, Copenhagen, Sotos Syndrome Genetics, Sotos Syndrome. This article was prepared by Biotech Week editors from staff and other reports. Copyright 2007, Biotech Week via NewsRx.com.
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