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19P13.13 Microdeletions

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19P13.13 Microdeletions 19p13.13 microdeletions rarechromo.org Sources 19p13.13 microdeletion The information in this A 19p13.13 microdeletion is a very rare genetic guide is drawn from four condition, in which there is a tiny piece of one of sources: the medical the 46 chromosomes missing. In this case, it is literature, the chromosome from the region known as p13.13, on database Decipher www. chromosome 19 (see diagram on page 3). The decipher.sanger.ac.uk, the missing piece of chromosome is very small Unique members’ database (less than 5Mb) and is called a microdeletion. and a survey of Unique The information in this guide is new as this is an members. For the emerging syndrome. There is likely to be a published medical range of effects from mild to more severe. literature, the first-named author and publication date Genes and chromosomes are given to allow you to The human body is made up of trillions of cells. look for the abstracts or Most of the cells contain a set of around 20,000 original articles on the different genes; this genetic information tells internet in PubMed the body how to develop, grow and function. (www.ncbi.nlm.nih.giv/ Genes are carried on structures called pubmed/). If you wish, you chromosomes, which carry the genetic material, can obtain most articles or DNA, that makes up our genes. from Unique. Chromosomes usually come in pairs: one This guide draws on chromosome from each parent. Of the 46 information from a survey chromosomes, two are a pair of sex of three members of chromosomes: XX (a pair of X chromosomes) in Unique in 2013, referenced females and XY (one X chromosome and one Y Unique, and the medical chromosome) in males. The remaining 44 literature. When this guide chromosomes are grouped into 22 pairs and are was written (Autumn 2013), numbered 1 to 22, approximately from the Unique had six members largest to the smallest. Each chromosome has a (two female, four male) with short (p) arm (from the French for small, petit) a 19p13.13 microdeletion. and a long (q) arm (see diagram on page 3). The six Unique members In general, the right amount of genetic material range in age from 2-21 is needed for correct development – not too years old with only one little and not too much. How an individual member older than 7 years develops, his/her personality, needs and old. There are seven people achievement, is influenced by both the genetic (five female, two male) material he or she has, and the environment in described in the medical which he or she lives. literature (Auvin 2009; Dolan 2010; Nimmakayalu Looking at chromosome 19p13.13 2013) ranging in age from 3 You can’t see chromosomes with the naked eye, -16 years old. but if you stain them and magnify them under a 2 microscope, you can see that each one has a distinctive pattern of light and dark bands. You can see these bands in the diagram of chromosome 19 (see diagram below). Each band of each chromosome contains millions of base pairs of DNA. Base pairs are the chemicals in DNA that form the ends of the ‘rungs’ of its ladder-like structure. People with a microdeletion of band 19p13.13 have between 0.16Mb to 2.39Mb deleted. 1 base pair = bp 1,000 base pairs = 1kb 1,000,000 base pairs = 1Mb 12,600,000 12,800,000 13,000,000 13,200,000 Note: the numbers in this diagram 13,400,000 refer to the human genome build 38 (hg38; see page 4 for more details). 13,600,000 Your child’s report may refer to a different genome build. Please contact Unique or your genetic 13,800,000 specialist for any help with Chromosome 19 understanding the report. Genetic testing Microdeletions of chromosome 19 are too small to be seen down even the highest powered microscope. Molecular DNA technology gives a more precise understanding of the size and position of the microdeletion. This is important as scientists identify genes and pinpoint their location on chromosomes. Genetic testing Techniques that are commonly used include FISH and microarrays: Fluorescence in situ hybridisation (FISH) uses fluorescent dyes to visualise under a microscope the number of copies of small sections of chromosomes. Unique publishes a separate guide to FISH However, rare chromosome disorders may be caused by subtle changes in the chromosomes that are too small to see using a microscope. Microarray comparative genomic hybridisation (array CGH) is a sensitive technique which shows gains (and losses) of tiny amounts of DNA throughout the chromosomes. Array CGH identifies duplicated, disrupted or absent DNA. Unique publishes a separate guide to array CGH. 3 A microarray will tell you the size of the deletion: arr [hg38] 19p13.13 (13155005-13554043)x1 dn arr The analysis was by array (arr) comparative genomic hybridisation (cgh) hg 38 Human Genome build 38. This is the reference DNA sequence that the base pair numbers refer to. As more information about is the human genome is found, new ’builds‘ of the genome are made and the base pair numbers may be adjusted. 19p13.13 The chromosome involved is 19, band 13.13 of the short p arm 13016005 – 13415043 The region from base pair 13155005-13554043 has been lost. By taking the first number from the second, you get 399,038 (approximately 0.4Mb).This is the number of base pairs that are missing x1 One copy of the segment of band 19p13.13, not two – one on each chromosome 19 – as you would normally expect. dn de novo – Latin for anew, meaning that the microdeletion has arisen for the first time in that individual and is not inherited from either parent. pat means inherited from the father; mat means inherited from the mother). Emerging phenotype: what to expect Chromosome changes involving chromosome 19 are uncommon and microdeletions are rarely reported. Only six Unique members) have a 19p13.13 microdeletion. Recently, seven people with deletions of 19p13.13 were published in the medical literature (Auvin 2009; Dolan 2010; Nimmakayalu 2013). Another person was described with a deletion which includes part of the 19p13.13 region but mainly covers the 19p13.2 region and is detailed in the Unique’s 19p13.2 microdeletion information guide (http://www.rarechromo.org/ information/Chromosome%2019/19p13.2%20microdeletions%20FTNW.pdf) (Lysy 2009). This is an emerging syndrome. The most consistent features are: Feeding/Digestion - Some children with a 19p13.13 may have difficulties with feeding and digestion, with reports of constipation and abdominal pain in some cases. It may also be difficult to introduce solid food. Growth - Children may be tall with a large head. Sitting, moving, walking (gross motor skills): Delay in learning to sit, move and walk is likely; walking may be unsteady and hypotonia (low muscle tone) is common. 4 Hand-eye coordination, dexterity and self-care (fine motor skills): Delay is likely. Children might need extra support with toilet training. Speech and language: Communication problems are frequently reported; children often have significantly delayed speech development. In some people, speech may be minimal and sign language may be helpful. Learning: Learning (intellectual) disabilities occur in children with a 19p13.13 microdeletion. Children are likely to need support with their learning. The amount of support needed varies. Communication difficulties are likely to affect children’s ability to learn. Eyesight: Eye problems are common and children may need glasses at a young age. An underdeveloped optic nerve (optic nerve hypoplasia) is present in some children and squints (strabismus) in over half of children Seizures: Seizures occur in approximately half of children Pregnancy and birth Most children were born at term after an uneventful pregnancy. Mothers do not generally report significant problems in pregnancy. Birth weights are known for nine children and were in the range 2.1kg – 4.1kg (4lb 11oz – 9lb ) (Dolan 2010; Nimmakayalu 2013; Unique), with an average birth weight of 3.28kg (7lb 3oz). Newborn Children often do not have obvious signs at birth. Unique members and individuals in the medical literature did not show any features of a 19p13.13 microdeletion at birth, other than characteristics that occur quite commonly in newborn babies, for example, jaundice. No Unique members had low Apgar scores (measure of baby’s wellbeing at birth). She was very healthy at birth” One child was born prematurely: He was born at 35 weeks, 5 days and went straight into the special care baby unit as he was grunting when he was born and couldn’t catch his breath. He stayed in there until he was able to feed, which was 2 weeks” In the medical literature one new baby had difficulty feeding due to a tongue- tie. This occurs when the thin piece of skin under the baby's tongue is very short and restricts the movement of the tongue. The skin can be snipped painlessly in young babies, but older babies usually have an anaesthetic (Dolan 2010). Another newborn had hypotonia and severe constipation (Auvin 2009). 5 Feeding/digestion Some children may have difficulties with feeding and digestion, particularly when solid food is introduced. Unique members do not describe any particular issues with breastfeeding or bottle-feeding but weaning to solid food can be problematic (Decipher; Unique). Two children found eating solid foods difficult; one was only eating 6-7 month stage baby food at 17 months old and the other was prone to choking due to oral hypotonia (low muscle tone around the mouth) and lack of coordination (Unique). Two children were sensitive to the texture of solid food (see sensory issues under ‘Behaviour’, page 11).
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