2q23.1 microdeletion syndrome rarechromo.org Sources 2q23.1 microdeletion syndrome and A 2q23.1 microdeletion is a rare genetic condition caused by a tiny missing part of one of the body’s 46 chromosomes – references chromosome 2. For healthy development, chromosomes The information should contain just the right amount of material – not too much in this guide is and not too little. Even a tiny piece of missing material can drawn partly disrupt development. from the published Background on Chromosomes medical literature. The Chromosomes are structures found in the nucleus of the first-named body’s cells. author and Every chromosome contains thousands of genes which may be publication date thought of as individual instruction booklets (or recipes) that are given to allow contain all the genetic information telling the body how to you to look for develop, grow and function. Chromosomes (and genes) usually the abstracts or come in pairs with one half of each chromosome pair being original articles inherited from each parent. Humans have 23 pairs of on the internet in chromosomes giving a total of 46 individual chromosomes. Of PubMed (http:// www.ncbi.nlm.ni these 46 chromosomes, two are the sex chromosomes that h.gov/pubmed/). determine gender. Females have two X chromosomes and If you wish, you males have one X chromosome and one Y chromosome. The can obtain most remaining 44 chromosomes are grouped in 22 pairs, numbered articles from 1 to 22 approximately from the largest to the smallest. Each Unique. In chromosome has a short or petit (p) arm (shown at the top in addition, this the diagram on page 3) and a long (q) arm (the bottom part of leaflet draws on the chromosome). information from a survey of Chromosome Deletions members of A sperm cell from the father and an egg cell from the mother Unique conducted in each carries just one copy of each chromosome. When they 2013, referenced join together they form a single cell that now carries two Unique. When copies of each chromosome. This cell must make many copies this guide was of itself (and all the chromosomes and genetic material) in written in April order to make all of the many cells that form during human 2013 Unique had growth and development. Sometimes during the formation of 15 member the egg or sperm cells or during this complicated copying and families with a replication process, parts of the chromosomes can break off or microdeletion at become arranged differently from usual. People with a 2q23.1 2q23.1 ranging in age from a 1- microdeletion have one intact chromosome 2, but a piece from year-old to a 13- the long arm of the other copy is missing. Therefore it is year-old. believed that most of the clinical difficulties are probably caused by having only one copy (instead of the usual two) of a gene or number of genes from the missing piece. We are still learning the about the specific jobs or functions of the genes in 2 this region. It is important to keep in mind that a child’s other genes, environment and unique personality also help to determine future development, needs and achievements. Looking at 2q23.1 You can’t see chromosomes with the naked eye, but if you stain them and magnify them under a 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 the long arm of chromosome 2 on the right. Band 2q23.1 contains around 1.2 million base pairs. This sounds a lot but it is actually quite small and is only 0.04 per cent of the DNA in each cell and only half a per cent of the DNA on chromosome 2. Base pairs are the chemicals in DNA that form the ends of the ‘rungs’ of its ladder-like structure. p arm Even if you magnify the chromosomes as much as possible, to about 850 times life size, a chromosome 2 with the microdeletion at q23.1 looks normal. People who have missing material on a chromosome are said to have a deletion but when the amount is so small that it can’t be seen even under a high-powered microscope, it is called a microdeletion. The 2q23.1 microdeletion centromere can only be found using molecular or DNA technology, in particular a technique using microarrays (array- CGH), that shows gains and losses of tiny amounts of DNA throughout the genome and can demonstrate whether particular gene(s) are present or not. One gene, MBD5, has been suggested to be responsible for Band 2q23.1 most, if not all, of the features of 2q23.1 microdeletion syndrome (see Research involving 2q23.1 on page 17). This guide includes descriptions of people who have a 2q23.1 microdeletion and also people who have a mutation or deletion of the MBD5 gene. q arm 1 base pair = bp 1,000 base pairs = 1kb 1,000,000 base pairs = 1Mb 3 Your geneticist or genetic counsellor will be able to tell you about the points where the chromosome has broken in your child. With a 2q23.1 microdeletion, the results are likely to read something like the following example: arr[hg19] 2q23.1(148,867,234-149,172,531)x1 arr The analysis was by array (arr) comparative genomic hybridisation (cgh) hg19 Human Genome build 19. This is the reference DNA sequence that the base pair numbers refer to. As more information about the human genome is found, new “builds” of the genome are made and the base pair numbers may be adjusted 2q23.1 The chromosome involved is 2 and the position of the deletion is in band q23.1 148,867,234-149,172,531 The base pairs between 148,867,234 and 149,172,531 have been shown to be deleted. Take the first long number from the second and you get 305,297 (0.305 Mb or 305kb). This is the number of base pairs that are deleted x1 means there is one copy of these base pairs, not two – one on each chromosome 2 – as you would normally expect 2q23.1 microdeletion syndrome The first published description of a person with a 2q23.1 microdeletion was in 2009. There have since been around 100 cases reported in the medical literature worldwide. When a particular set of developmental features occurs in a recognisable and consistent pattern in enough people, as a result of a single cause, the condition is called a syndrome. The features of a 2q23.1 microdeletion do occur in this way, so the disorder is often known as 2q23.1 microdeletion syndrome. The deletion occurs equally often in boys and girls (Waggenstaller 2007; Jaillard 2009; van Bon 2010; Williams 2010; Chung 2011; Noh 2012; Chung 2012; Bonnet 2013; Hodge 2013). How much do we know? Comparing different children and adults with 2q23.1 microdeletions shows that some effects seem to be very broadly similar. This information guide tells you what is known about those effects. Comparing your child’s array results with others, both in the medical literature and within Unique, can help to build up a general picture of what to expect. But there will still be differences, sometimes quite marked, between your child and others with an apparently similar array result. It is very important to see your child as an individual and not to make direct comparisons with others with the same chromosome test results. After all, each of us is unique. Most common features Every person with a 2q23.1 microdeletion is unique and so each person will have 4 different medical and developmental concerns. Additionally, no one person will have all of the features listed in this information guide. However, a number of common features have emerged: Children are likely to need support with learning. The amount of support needed by each child will vary Seizures Speech and language delay Behavioural difficulties such as autistic spectrum disorder or attention deficit hyperactivity disorder Sleep disturbances Short stature What is the outlook? We can’t be certain yet but there appears to be no reason why people who are healthy should not enjoy a normal lifespan. However, regression has been reported in three out of more than a hundred people in the medical literature. A 44-year-old experienced behavioural regression with a significant increase in skin picking and obsessive compulsive activities. A 4-year-old girl walked independently at 28 months, but at 4 years had lost some of her vocabulary and the ability to walk, standing only with support. A 6-year-old had progressive difficulties with fine motor skills and balance, worsening behaviour and loss of ability to draw lines and circles (Chung 2011; Noh 2012; Hodge 2013). Sadly, one woman developed seizures from the age of 9 months and died at 26 years because of seizures. Pregnancy and birth Many pregnancies were uncomplicated, and babies were born at or near their expected due date Many mothers (13/22) carrying babies with a 2q23.1 microdeletion experienced no pregnancy problems, had a normal delivery and only discovered their baby was affected after the birth. However, pregnancy complications in mothers carrying a baby with a 2q23.1 microdeletion have been reported. Two babies were delivered by emergency caesarean (C-) section at 35 and 36 weeks; one due to a placental abruption (the placenta separates from the wall of the uterus before birth) at 30 weeks and the other due to pre-eclampsia (a sudden increase in blood pressure and the presence of excess protein in the urine.