Tetrasomy 9p FTNW - Unique - The Rare Chromosome Disorder ...

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Why are some people with tetrasomy 9p more severely affected than others? There are quite a few reasons. One is likely to be the size of the isochromosome, although researchers do not always agree how important it is if you have a larger isochromosome with more chromosome material. Some believe it matters and children with additional material from 9q seem more severely affected (Chen 2007; Wisniewski 1978). Others are not so sure (Stumm 1999). It is also true that individual differences between children even with the same karyotype can be fairly marked. Often the karyotype from a blood or skin sample shows two different cell lines, one with tetrasomy 9p and one with normal chromosomes. Where there are two different cell lines within the same tissue, it is known as mosaicism. When all the cells show tetrasomy 9p, it is known as non-mosaicism. Babies found to have mosaic tetrasomy 9p are likely to do better than those with non-mosaic tetrasomy 9p, especially in terms of survival beyond the newborn period. 47,XY,+i(9)(p10)[4]/46,XY[16] This is a boy in whom 20 cells were tested. Four [4] showed tetrasomy 9p while sixteen [16] showed a normal karyotype for a boy or man. The cells tested for the karyotype are most often taken from blood. In tetrasomy 9p, blood cells often show non-mosaicism (that is, only tetrasomy 9p cells), even where there is mosaicism or indeed cell lines with only normal cells in other parts of the body. So a baby who has only had a blood test may be thought to have non-mosaic tetrasomy 9p, when in fact there is mosaicism in other tissues. For this reason, most genetics centres recommend testing samples from more than one part of the body, usually either from the skin or from inside the cheek (Lloveras 2004). Common sense might suggest that when a higher proportion of tetrasomy 9p cells is found, the effects are likely to be more severe. But this is not necessarily true. One reason for this discrepancy may be varying proportions of tetrasomy 9p cells in tissues of importance fro development, tissues which have not been investigated. Are there people with tetrasomy 9p who are healthy, have no major birth defects and have developed normally? Yes, there are. Out of 47 reports in the medical literature, there are three people with apparently normal development and a possible fourth. One adult is an accountant and was discovered to have tetrasomy 9p when infertility was investigated. Another adult was investigated for skin lesions. Another case is of a child who has developed normally to the age of five, although he showed growth delay before birth; a six-month-old baby also had no apparent abnormalities at the age of 6 months (McAuliffe 2005; Lloveras 2004; Sait 2003; Nakamura 1990). Among Unique’s 13 members, two children were only diagnosed after being investigated for developmental delay in the late primary school or early secondary school years. Why is tetrasomy 9p so variable? There are four key reasons: Mosaic or not mosaic – when only tetrasomy 9p cells and no normal cells are found in both blood and skin cells or amniotic fluid, the effects are likely to be more obvious and more severe. Babies with mosaic tetrasomy 9p survive the newborn period better. 4
Tissue-limited mosaicism – The proportions of tetrasomy 9p cells are different in different body tissues. In blood there are more tetrasomy 9p cells and sometimes no normal cells are found. In other tissues, especially skin and mucous membranes, the proportion of tetrasomy 9p cells is usually lower and no tetrasomy 9p cells may be found. Organs, such as the brain and lungs, may have different proportions again and this variability is very likely to affect the outcome (Lloveras 2004; Dhanda 2002). Size of isochromosome – that is, the amount of extra chromosome material. Common sense suggests that those with larger extra chromosomes will be more severely affected. Specific duplicated regions – a boy with three copies of the section of chromosome 9 between band p13 and p22 shared some similarities with children with an isochromosome 9p, but had no major anomalies apart from enlarged ventricles within the brain. This could suggest that the part of 9p that he did not have extra copies of (9p23 to the tip of 9p) is the part that causes important birth defects (Verheij 1999). Most likely features among those with mosaic tetrasomy 9p - found in at least half of all children and adults reported or described so far (de Azevedo 2003; Dhanda 2002; Unique) Developmental delay In 4/7 Unique cases, a delay in expected development was the first sign of anything wrong. Signs were first noticed between three months and early secondary school age. Central nervous system (brain and spinal cord) anomaly Abnormal features of arms or legs. These can include dislocated joints and clubfeet Growth delay before or after birth Heart defects Abnormalities of the kidneys or urinary system. In boys, minor anomalies of the genitals or undescended testicles are common At birth, wide gaps between the bony plates of the skull. The front soft spot (fontanelle) may be large Short neck, sometimes with excess skin Typical facial features including wide set eyes, small jaw (chin), oddly formed or positioned ears and a bulbous or beaked nose Cleft lip, palate or a high-arched palate Other typical features Unusually formed nails; a single crease across the palm; incurving fingers, especially the fifth finger; short hands and feet with small toe and finger joints Widely spaced eyes; small skin folds across the inner corner of the eyes; eyes that slant somewhat downwards; a small lower jaw, set back from the upper jaw; downwards slanting mouth Low muscle tone, making the body feel floppy (hypotonia) Unusual head size – small (microcephaly) or large (macrocephaly). Enlarged fluidfilled ventricles within the brain (hydrocephaly) Strabismus (squint) or short sight (myopia) Dimple near the base of the spine Sunken eyes due to eyeball being recessed within the orbit Missing or underdeveloped bones 5
Page 1 and 2: Tetrasomy 9p
Page 3: The karyotype Your genetic speciali
Page 7 and 8: A child with tetrasomy 9p Two babie
Page 9 and 10: A wide variety of specific abnormal
Page 11 and 12: A mild to moderate hearing loss app
Page 13 and 14: families, but one Unique family who
Page 15 and 16: A multicystic kidney may be removed

Tetrasomy 9p FTNW - Unique - The Rare Chromosome Disorder ...

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