Genetic outcomes in children with developmental language disorder: a systematic review

Diagnosing Down Syndrome, Cystic Fibrosis, Tay-Sachs Disease And Other Genetic Disorders

Sometimes, a pediatrician will suspect that a child has a genetic disorder based on the child's symptoms or on the presence of dysmorphic features. For example, if a child has coarse facial features and developmental delays, a pediatrician may have reason to believe that the child has a form of mucopolysaccharidosis. Mucopolysaccharidosis is a family of diseases caused by an enzyme deficiency that leads to the accumulation of glycosaminoglycans (GAGs) within the lysosomes of cells. In one particular variant of this disease known as mucopolysaccharidosis I (MPS I), a deficiency of the enzyme alpha-L-iduronidase causes a build up of GAGs in tissues and organs, which in turn leads to a host of signs including skeletal deformities, coarse facial features, enlarged liver and spleen, and mental deficiencies. Because of the progressive nature of MPS I, a child might not exhibit noticeable symptoms until one to three years of age or even later, depending on severity.

There are a number of reasons that a pediatrician might refer a child to see a geneticist. Geneticists can confirm or rule out a physician's diagnosis based on the findings of a physical exam and various tests. In the case of a child with suspected MPS, if the enzymatic deficiency associated with the disorder is confirmed via testing, DNA analysis may also be performed to determine the exact genetic mutation causing the disorder. Because MPS I is inherited in an autosomal recessive fashion, identification of the mutation can allow the family to undergo carrier screening, as well as prenatal or preimplantation diagnosis in any future children.

Inherited Partial Duplication Of Chromosome No. 15

A boy with unusual facial appearance and mental retardation was found to have duplication for the distal half of the long arm of chromosome No. 15 and possibly deficiency for the distal end of the long arm of No. 21. The chromosome abnormality was inherited from his mother, who had a translocation involving chromosomes Nos. 15 and 21. Giemsa-banding localized the break point in chromosome No. 15 just distal to the intense band at the midportion of the long arm. The break point in chromosome No. 21 appeared to be at the distal end of the long arm. The difficulty encountered in cytogenetic analysis of the propositus with conventional staining, the importance of chromosome analysis of the parents, and the application of differential staining techniques are also presented.

Chromosomal Duplication Of Band 10p14 Segregating Through Four Generations

Editor—In recent years the increased resolution that can be obtained with GTL banded prometaphase chromosomes has led to the recognition of abnormalities involving small regions of the karyotype. Some of these abnormalities involve deletion or duplication of only one or two chromosomal bands and are associated with a sufficiently mild phenotype as to be directly inherited. Nevertheless, directly inherited duplication of visible chromosomal material is an uncommon category of chromosomal abnormality that has been reported for a small number of specific regions of the karyotype, including 2q11.2-q21.1,1 6p23-pter,26q22-q24,3 7p12-p13,4 8p23.1,59p22-p24,6 14q13-q22,7 15q12,8and 18p.9 Some of these duplications are without apparent phenotypic effect,5 8 while in other cases there are mild phenotypic abnormalities.1 2 Genomic imprinting has been shown to have an effect on the phenotypic expression of dup(15)(q12)8 and also dup(6)(q24),3 and is a point for consideration in other small duplications.

Tandem duplications occur when a second copy of a chromosomal region is inserted adjacent to the original region. They have been reported for a number of chromosomal segments,2 9 although not previously for band 10p14. Microduplication and microdeletion of chromosomal material is presumed to occur as a meiotic event following uneven crossing over between short sequences of highly similar DNA inserted at two close, but not contiguous sites along the chromosome.10 11 Tandem duplication is generally de novo with rare cases reported of direct inheritance.3-6 8 9To be balanced, an intrachromosomal duplication would have to be associated with chromosomal deletion of the specific region in the other homologue and to have occurred postzygotically. To our knowledge, this type of balanced chromosomal rearrangement has not been reported as a constitutional abnormality. We describe here a previously unreported small …

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