Inform Network Support Rare Chromosome Disorder Support Group G1, The Stables, Station Road West, Oxted, Surrey RH8 9EE, United Kingdom Tel: +44(0)1883 723356 [email protected] I www.rarechromo.org Join Unique for family links, information and support. Unique is a charity without government funding, existing entirely on donations and grants. If you can, please make a donation via our website at Pallister-Killian www.rarechromo.org Please help us to help you! Websites, Facebook groups http://pkskids.net syndrome http://pkskids.ning.com www.pks.org.au www.pksitalia.org www.facebook.com/pages/Pallister-Killian-Syndrome-PKS www.facebook.com/pages/Sindrome-Pallister-Killian (in Spanish) Unique mentions other organisations’ message boards and websites to help families looking for information. This does not imply that we endorse their content or have any responsibility for it. This information guide is not a substitute for personal medical advice. Families should consult a medically qualified clinician in all matters relating to genetic diagnosis, management and health. Information on genetic changes is a very fast-moving field and while the information in this guide is believed to be the best available at the time of publication, some facts may later change. Unique does its best to keep abreast of changing information and to review its published guides as needed. This booklet was compiled by Unique and reviewed by Dr Michel Vekemans, Department of Genetics, Hopital Necker Enfants Malades, Paris, France 2004 and by Unique’s chief medical advisor, Professor Maj Hultén, Professor of Reproductive Genetics, University of Warwick, UK. 2005 (PM). This booklet was updated by Unique in 2016 (AP) and reviewed by Dr Moira Blyth, Consultant in Clinical Genetics, Chapel Allerton Hospital, Leeds, UK. Copyright © Unique 2016 Rare Chromosome Disorder Support Group Charity Number 1110661 Registered in England and Wales Company Number 5460413 rarechromo.org 24 Pallister-Killian Syndrome groups worldwide who are studying the different aspects of this syndrome. Of particular mention is the recent study (Blyth 2015), referred to often in this Pallister-Killian syndrome is caused by the presence of a small extra chromosome in some cells of the body. The extra chromosome is made up of guide, which describes findings from the developmental assessment and clinical two mirror copies of the short (p) arm of chromosome 12. This type of examination of twenty-two people with Pallister-Killian syndrome. Another large chromosome is called an isochromosome. Cells usually have two copies of scale study of 59 individuals with PKS carried out in the US (Wilkens 2012) is a chromosome 12, each containing a ‘p’ and a ‘q’ arm. The addition of two more ‘p’ great source of information and is also often referred to in this guide. arms of chromosome 12 results in cells having four copies of this part of Genes chromosome 12 instead of two. This is referred to as mosaic tetrasomy 12p. The critical region of chromosome 12p that causes PKS is thought to lie Mosaic means that the extra chromosome is not found in all cells and tetrasomy somewhere between the end of the p arm and band 12.3. This region is known to means that there are four copies as shown in the image below. contain over 300 genes. A change in expression of any of these genes can consequently cause altered expression of other genes on other chromosomes. A recent study (Kaur 2014) identified a PKS gene expression profile using 12p 12p 12p fibroblast cells from patients with Pallister-Killian syndrome. The report suggests a critical region on 12p13.31 (this band contains an estimated 129 Cells with tetrasomy 12p genes) and identified a change in expression of 354 genes. have two copies of 12p chromosome 12 and an Advice from parents of children with PKS extra isochromosome PKS is a rollercoaster, great highs and great lows, celebrate all those tiny little made from two opposite 12p achievements because for our kids a smile is massive, holding a rattle is Isochromosome facing p arms of 12q 12q massive. But also there seems to be a difference in how badly our children are chromosome 12 affected, do not give up hope, trust your judgment, a lot of the time we are the experts in our child's care. Laugh a lot with your child. Spoil them as much as you can. Expect nothing Two copies of from them. Marvel in their achievements no matter how small. Chromosome 12 It's all too easy to get weighed down with what they can't do, instead of The effects of mosaic tetrasomy 12p are caused by the genes carried on the concentrating on what they can. And just remember that there are others that extra chromosome. Typically, these genes cause a distinctive syndrome called you can talk to that know exactly how you feel. Pallister-Killian Syndrome (PKS). However, for reasons that are not well This was our first exposure to the special needs world. We reached out to understood, the severity of the effects of having mosaic tetrasomy 12p varies social media and found a parent support group. We ordered special needs enormously between people. Therefore, not all children diagnosed as having catalogs to see what type of equipment would make our lives easier. We have mosaic tetrasomy 12p will have classical Pallister-Killian Syndrome. Only those always made sure to take care of each other since it can be a demanding who are recognisably affected by the extra DNA are described as having parental role. We get respite help and ask for assistance because we know that classical PKS and these are the children who will be considered in this booklet. we are better parents when we have taken care of ourselves. We also share our story with whomever will listen and hope that it gives others an appreciation and Sources gratitude for life. We celebrate the little things, honor the quirky things about The information in this booklet is drawn from published medical literature and our family but it wasn’t always like this. We had to evolve to get to this place. The information from Unique members. The first-named author and publication date first few years were so new and there was a lot of fear. At some point, we from articles in the medical literature are given to allow you to look for the decided to stop living with fear running our days and to just be in the moment abstracts or original articles on the internet in PubMed (http://www.ncbi.nlm. more. Everything became lighter then. nih.gov/pubmed). If you wish, you can obtain most articles from Unique. Unique The biggest issue with PKS is that not 1 child is the same, to compare 1 child member surveys were carried out in 2004 and 2016. In addition to this, Unique against another with this syndrome is not the right thing to do. You need to take held an international study weekend in 2010. Please read our Pallister-Killian each day and milestone as it comes and not set expectations, they’ll get there Syndrome Study Weekend Report available on our Disorder Guides webpage. when and if they can. Typical symptoms go out the window. 2 23 The additional isochromosome usually comes from the mother but sometimes Diagnosis comes from the father. This type of chromosome error is more common among Chromosome disorders are usually diagnosed by examining DNA taken from older parents and among Unique members many were older. Mothers’ ages white blood cells. However, children with mosaic tetrasomy 12p often appear to ranged from 20 to 42 while fathers’ ages ranged from 28 to 50. The average have normal chromosomes in their blood cells, so the diagnosis is usually made maternal age in a recent study of 59 individuals with PKS (Wilkens 2012) was from skin cells or cells taken from inside the cheek (buccal mucosa). Samples 31.7 years and paternal age 34.9 years. Other studies have also reported a link to may be analysed by a simple chromosome counting technique (karyotyping) or parental age (Wenger 1988; Blyth 2015). chromosomes may be analysed more closely using a technique called The error is thought to arise during the process that leads to the formation of fluorescence in situ hybridization (FISH) or array comparative genomic the egg and sperm cells. During this process, a cell with 46 chromosomes (23 hybridisation (CGH). The results you are given will depend upon the way your pairs) usually separates to make two egg or sperm cells with 23 single child’s samples were analysed. chromosomes in each. A fairly common error is a failure of this natural separation (non-disjunction), so that one of the new cells contains both copies of Results of a chromosome test chromosome 12. The 12p isochromosome is then created when one Karyotype example chromosome 12 splits horizontally near the centromere instead of the usual Most cells in our body contain two copies of each ‘autosomal’ chromosome vertical divide. The two copies of the long arm (q arm) are subsequently lost. (numbered 1 to 22) and two ‘sex’ chromosomes, either 2 X’s (female) or an X and Mosaicism then arises soon after conception when the isochromosome is lost a Y (male). When a cell sample is taken and prepared in a specific way, the from one or more cell lines. The alternative scenario is that the additional chromosomes can be seen under a microscope and counted. This is called a chromosome has arisen from a mistake in cell division after conception (Turleau karyotype, an example of which, for somebody with tetrasomy 12p, can be seen 1996; Dutly 1998; Struthers 1999; Dufke 2001).