{"id":753,"date":"2026-08-10T23:45:08","date_gmt":"2026-08-10T21:45:08","guid":{"rendered":"https:\/\/kleefstrasyndrome.com\/?page_id=753"},"modified":"2026-08-20T23:18:15","modified_gmt":"2026-08-20T21:18:15","slug":"kleefstra-clinical-guidelines-2026","status":"publish","type":"page","link":"https:\/\/kleefstrasyndrome.com\/en\/kleefstra-clinical-guidelines-2026\/","title":{"rendered":"International guidelines for Kleefstra syndrome (2026)"},"content":{"rendered":"<p class=\"wp-block-paragraph\">In 2026 were published <strong>first international, evidence-based clinical practice guidelines for Kleefstra syndrome type 1 (KLEFS1)<\/strong>.<\/p>\n\n\n\n<p class=\"wp-block-paragraph\">This is an important milestone for the Kleefstra community, as recommendations regarding diagnosis, genetic counseling, development and communication, mental health and loss of skills, epilepsy, sleep, vision and hearing, the heart, growth and metabolism, constipation, as well as family support and the transition to adulthood, were gathered for the first time into a single scientific framework.<\/p>\n\n\n\n<p class=\"wp-block-paragraph\">The instructions include a total of <strong>66 clinical recommendations<\/strong> and are designed to serve as a minimum international standard of care for individuals with KLEFS1.<\/p>\n\n\n\n<blockquote class=\"wp-block-quote is-layout-flow wp-block-quote-is-layout-flow\">\n<blockquote class=\"wp-block-quote is-layout-flow wp-block-quote-is-layout-flow\">\n<p class=\"study-significant wp-block-paragraph\" style=\"font-size:16px\">Important clarification: This page is a Greek informative translation and explanation of the international guidelines. It is not an official Greek translation of the scientific document and does not replace personalized medical evaluation.<\/p>\n<\/blockquote>\n<\/blockquote>\n\n\n\n<blockquote class=\"wp-block-quote is-layout-flow wp-block-quote-is-layout-flow\">\n<blockquote class=\"wp-block-quote is-layout-flow wp-block-quote-is-layout-flow\">\n<p class=\"wp-block-paragraph\"><\/p>\n<\/blockquote>\n<\/blockquote>\n\n\n\n<hr class=\"wp-block-separator has-alpha-channel-opacity\"\/>\n\n\n\n<h3 class=\"wp-block-heading has-text-color has-link-color wp-elements-1\" style=\"color:#8b1aba;font-size:18px\">Which syndrome do the guidelines refer to?;<\/h3>\n\n\n\n<p class=\"wp-block-paragraph\">The instructions apply exclusively to <strong>Kleefstra syndrome type 1 (KLEFS1)<\/strong>, which is caused by a gene function disorder <em>EHMT1<\/em>.<\/p>\n\n\n\n<p class=\"wp-block-paragraph\">This is important because in the past the term \u00abKleefstra syndrome type 2\u00bb was used for a disorder related to <em>KMT2C<\/em>. The authors of the new guideline point out that it has now been established that the two conditions are distinct and, therefore, these specific recommendations pertain to <strong>only the KLEFS1 related to the EHMT1<\/strong>.<\/p>\n\n\n\n<p class=\"wp-block-paragraph\">The estimated frequency of KLEFS1 is reported in the guideline as approximately <strong>1 in 36,000 people<\/strong>.<\/p>\n\n\n\n<hr class=\"wp-block-separator has-alpha-channel-opacity\"\/>\n\n\n\n<h3 class=\"wp-block-heading has-text-color has-link-color wp-elements-2\" style=\"color:#8b1aba;font-size:18px\">Why were special guidelines needed?;<\/h3>\n\n\n\n<p class=\"wp-block-paragraph\">Until today, much of the knowledge about Kleefstra syndrome has been fragmented across individual publications, small patient series, and the experience of specialized centers.<\/p>\n\n\n\n<p class=\"wp-block-paragraph\">This resulted in the monitoring of a person with Kleefstra varying significantly depending on the country, the center, or even the doctor monitoring them.<\/p>\n\n\n\n<p class=\"wp-block-paragraph\">The new guidelines were created with three main objectives:<\/p>\n\n\n\n<ul class=\"wp-block-list\">\n<li>to improve the quality of care,<\/li>\n\n\n\n<li>to establish a common minimum international monitoring standard,<\/li>\n\n\n\n<li>and to support shared decision-making among healthcare professionals, people with Kleefstra, and their families.<\/li>\n<\/ul>\n\n\n\n<p class=\"wp-block-paragraph\">Their development involved <strong>43 professionals and family representatives from 15 countries<\/strong>, with specialties that included clinical genetics, pediatrics, neurology, psychiatry, psychology, cardiology, genetic counseling, speech therapy, and research. Parents of individuals with KLEFS1 also actively participated in the group.<\/p>\n\n\n\n<p class=\"wp-block-paragraph\">The literature was systematically searched in the PubMed, Embase, CINAHL, and PsycINFO databases, and the search was updated through May 2024. A total of 72 studies were included in the review. In parallel, focus groups with parents and an international consensus meeting were conducted.<\/p>\n\n\n\n<div class=\"wp-block-group\"><div class=\"wp-block-group__inner-container is-layout-constrained wp-block-group-is-layout-constrained\">\n<p class=\"has-text-align-center is-style-info wp-block-paragraph\"><strong><em>An important scientific caveat <\/em><\/strong><br><strong><em><br><\/em><\/strong>Because Kleefstra syndrome is rare, many of the available studies are small or involve individual cases. The authors themselves acknowledge that the quality of the available scientific evidence is low for several issues.<br><br>Therefore, the 66 recommendations are not all based on large clinical trials. They combine available scientific evidence with the expertise of international experts and the experience of the families themselves.<br>This is particularly important to take into account when the guidelines refer to specific therapeutic interventions.<\/p>\n<\/div><\/div>\n\n\n\n<hr class=\"wp-block-separator has-alpha-channel-opacity\"\/>\n\n\n\n<h3 class=\"wp-block-heading has-text-color has-link-color wp-elements-3\" style=\"color:#8b1aba;font-size:18px\">The most important instructions at a glance<\/h3>\n\n\n\n<p class=\"wp-block-paragraph\">For a family that has just received the diagnosis, some of the most important points are the following:<\/p>\n\n\n\n<ul class=\"wp-block-list\">\n<li>reference to <strong>clinical genetics team<\/strong>,<\/li>\n\n\n\n<li>home <strong>cardiological evaluation<\/strong>,<\/li>\n\n\n\n<li>home <strong>audiological and ophthalmological evaluation<\/strong>,<\/li>\n\n\n\n<li>evaluation <strong>speech, language, and communication<\/strong>,<\/li>\n\n\n\n<li>timely examination of use <strong>Augmentative and Alternative Communication (AAC)<\/strong> when speech is not sufficient for everyday needs,<\/li>\n\n\n\n<li>regular monitoring of <strong>sleep<\/strong>,<\/li>\n\n\n\n<li>monitoring of <strong>behavioral and mental health at least once a year<\/strong>,<\/li>\n\n\n\n<li>monitoring of growth, weight, and metabolic health,<\/li>\n\n\n\n<li>active investigation and resolution of the <strong>constipation<\/strong>,<\/li>\n\n\n\n<li>and immediate evaluation when it appears <strong>sudden loss of skills or significant change in behavior, sleep, or functioning<\/strong>.<\/li>\n<\/ul>\n\n\n\n<p class=\"wp-block-paragraph\">In contrast, certain exams <strong>are not recommended as routine tests for everyone<\/strong>. For example, brain magnetic resonance imaging and an electroencephalogram are performed when there are specific clinical indications.<\/p>\n\n\n\n<p class=\"wp-block-paragraph\">Here are all 66 recommendations in detail.<\/p>\n\n\n\n<div class=\"wp-block-coblocks-accordion guidelines-page\">\n<div class=\"wp-block-coblocks-accordion-item\"><details><summary class=\"wp-block-coblocks-accordion-item__title has-background\" style=\"background-color:#f4e8ff\">1. Diagnosis and genetic testing<\/summary><div class=\"wp-block-coblocks-accordion-item__content\" style=\"border-color:#f4e8ff\">\n<p class=\"wp-block-paragraph\">KLEFS1 is caused by the loss of its normal function <em>EHMT1<\/em>. About half of the cases are related to pathogenic variants within the gene itself, while about half are related to copy number variations, mainly deletions of the 9q34.3 region. There are also rarer structural genetic alterations.<\/p>\n\n\n\n<h3 class=\"wp-block-heading recommendations-title\" style=\"font-size:18px\">What do the guidelines suggest<\/h3>\n\n\n\n<p class=\"wp-block-paragraph\"><strong>1.<\/strong> When a doctor observes features that raise suspicion of Kleefstra syndrome \u2014 or when parents themselves express well-founded concerns about the child's development \u2014 an appropriate evaluation should be performed and the need for genetic testing should be considered.<\/p>\n\n\n\n<p class=\"wp-block-paragraph\"><strong>2.<\/strong> In individuals with clinical suspicion of Kleefstra, the recommended initial genetic test is <strong>genome sequencing (GS)<\/strong> or, when that is not available, the <strong>exon sequencing (ES)<\/strong>, preferably as a trio test\u2014that is, with the child and both parents tested simultaneously.<\/p>\n\n\n\n<p class=\"wp-block-paragraph\">Ideally, the test should be able to detect not only sequence changes but also deletions, duplications, and other structural alterations.<\/p>\n\n\n\n<p class=\"wp-block-paragraph\">If the test does not yield a diagnosis, a chromosomal microarray (CMA) is recommended. Where GS\/ES is not available as a first-line test, CMA may be performed first, followed by GS\/ES if necessary.<\/p>\n\n\n\n<p class=\"wp-block-paragraph\"><strong>3.<\/strong> Anyone who has a pathogenic variant of <em>EHMT1<\/em> or even <strong>variant of uncertain clinical significance (VUS)<\/strong> he\/she should be referred to a clinical genetics team for evaluation, confirmation of the diagnosis, and genetic counseling.<\/p>\n\n\n\n<p class=\"wp-block-paragraph\"><strong>4.<\/strong> For individuals with a 9q34.3 deletion, specialized testing of the individual and their parents is recommended to determine whether either parent carries a balanced chromosomal rearrangement, which may affect the risk of recurrence in a future pregnancy.<\/p>\n\n\n\n<p class=\"wp-block-paragraph\"><strong>5.<\/strong> If the GS\/ES and chromosomal microarray are negative but the clinical suspicion remains strong, a more specialized evaluation of the <em>EHMT1<\/em> for very small deletions or duplications that may have been missed.<\/p>\n\n\n\n<p class=\"wp-block-paragraph\"><strong>6.<\/strong> In individuals with a very characteristic phenotype but a non-diagnostic genetic result \u2014 including certain VUS \u2014 additional tests can be considered, such as <strong>specific DNA methylation pattern (episignature)<\/strong>, or participation in research studies.<\/p>\n\n\n\n<h3 class=\"wp-block-heading practical-title\" style=\"font-size:18px\">What it means practically for the family<\/h3>\n\n\n\n<p class=\"wp-block-paragraph\">Genetic diagnosis should not end with the receipt of a lab result.<\/p>\n\n\n\n<p class=\"wp-block-paragraph\">The family must have the opportunity to discuss:<\/p>\n\n\n\n<ul class=\"wp-block-list\">\n<li>what exactly was found,<\/li>\n\n\n\n<li>How certain is the diagnosis,<\/li>\n\n\n\n<li>what it means for the specific person,<\/li>\n\n\n\n<li>if parental supervision is needed,<\/li>\n\n\n\n<li>what is the risk of recurrence,<\/li>\n\n\n\n<li>and what reproductive options are available.<\/li>\n<\/ul>\n<\/div><\/details><\/div>\n\n\n\n<div class=\"wp-block-coblocks-accordion-item\"><details><summary class=\"wp-block-coblocks-accordion-item__title has-background\" style=\"background-color:#f4e8ff\">2. Behavior and Mental Health<\/summary><div class=\"wp-block-coblocks-accordion-item__content\" style=\"border-color:#f4e8ff\">\n<h3 class=\"wp-block-heading\" style=\"font-size:18px\">Mental health is now a central part of Kleefstra&#x27;s care plan.<\/h3>\n\n\n\n<p class=\"wp-block-paragraph\">In the review used for the guidelines, the total lifetime prevalence of mental health and behavioral problems was estimated at approximately <strong>74%<\/strong>. Behavioral problems often appear as early as childhood, while psychiatric disorders become more frequent during adolescence and adulthood.<\/p>\n\n\n\n<h3 class=\"wp-block-heading recommendations-title\" style=\"font-size:18px\">What do the guidelines suggest<\/h3>\n\n\n\n<p class=\"wp-block-paragraph\"><strong>7.<\/strong> Behavior and mental health must be assessed during diagnosis and <strong>at least once a year thereafter<\/strong>.<\/p>\n\n\n\n<p class=\"wp-block-paragraph\">The evaluation must take into account:<\/p>\n\n\n\n<ul class=\"wp-block-list\">\n<li>any medications,<\/li>\n\n\n\n<li>associated health problems,<\/li>\n\n\n\n<li>changes in behavior,<\/li>\n\n\n\n<li>and the support or treatment the individual is already receiving.<\/li>\n<\/ul>\n\n\n\n<p class=\"wp-block-paragraph\"><strong>8.<\/strong> When significant behavioral or mental health difficulties are identified, a referral should be made to appropriate professionals, e.g., for autism evaluation, behavioral intervention, or pharmacotherapy when indicated.<\/p>\n\n\n\n<p class=\"wp-block-paragraph\"><strong>9.<\/strong> When there are symptoms that substantially affect daily life, self-care, social relationships, school, or work, an active referral to a psychiatrist or psychologist is recommended.<\/p>\n\n\n\n<p class=\"wp-block-paragraph\"><strong>10.<\/strong> For behaviors that create difficulties, the first approach must be personalized and based on an understanding of the function and potential causes of the behavior.<\/p>\n\n\n\n<p class=\"wp-block-paragraph\"><strong>11.<\/strong> One <strong>The sudden onset of new behavior or psychiatric symptoms, or a significant change in pre-existing symptoms, should not be ignored.<\/strong>. It requires active investigation and, where necessary, treatment.<\/p>\n\n\n\n<p class=\"wp-block-paragraph\">It is of particular importance to rule out physical causes that can worsen behavior or mental state, such as endocrine problems, vitamin deficiencies, pain, or constipation.<\/p>\n<\/div><\/details><\/div>\n\n\n\n<div class=\"wp-block-coblocks-accordion-item\"><details><summary class=\"wp-block-coblocks-accordion-item__title has-background\" style=\"background-color:#f4e8ff\">3. Loss of skills \u2013 regression<\/summary><div class=\"wp-block-coblocks-accordion-item__content\" style=\"border-color:#f4e8ff\">\n<p class=\"wp-block-paragraph\">One of the most important new elements of the guidelines is that <strong>regression of previously acquired skills<\/strong> It is officially recognized as a significant issue in Kleefstra.<\/p>\n\n\n\n<p class=\"wp-block-paragraph\">Episodes of significant impairment have been reported, primarily during adolescence and adulthood. The reported frequencies in published studies vary significantly, ranging from approximately 11% to 50%.<\/p>\n\n\n\n<p class=\"wp-block-paragraph\">May be affected:<\/p>\n\n\n\n<ul class=\"wp-block-list\">\n<li>speech and communication,<\/li>\n\n\n\n<li>motor skills,<\/li>\n\n\n\n<li>cognitive abilities,<\/li>\n\n\n\n<li>social and emotional functioning,<\/li>\n\n\n\n<li>autonomy and other daily living skills.<\/li>\n<\/ul>\n\n\n\n<p class=\"wp-block-paragraph\">In some cases they take precedence <strong>severe sleep problems or significant physical or psychological stressors<\/strong>.<\/p>\n\n\n\n<h3 class=\"wp-block-heading recommendations-title\" style=\"font-size:18px\">What do the guidelines suggest<\/h3>\n\n\n\n<p class=\"wp-block-paragraph\"><strong>12.<\/strong> Every person with suspected or confirmed loss of skills must be referred <strong>immediately<\/strong> to an experienced clinician, such as a psychiatrist, neurologist, or pediatrician, for a thorough investigation of the cause and treatment.<\/p>\n\n\n\n<p class=\"wp-block-paragraph\"><strong>13.<\/strong> It is important to use standardized assessment tools for adaptive functioning in order to objectively record its change and progress.<\/p>\n\n\n\n<p class=\"wp-block-paragraph\"><strong>14.<\/strong> The guideline states that in new or ongoing regression episodes, the use of can be evaluated by a psychiatrist <strong>olanzapine<\/strong>, especially when psychosis and severe insomnia coexist. Potential catatonia requires a different therapeutic approach.<\/p>\n\n\n\n<p class=\"wp-block-paragraph\">This specific recommendation <strong>it is not a guideline for initiating a medication from the family<\/strong> and the treatment must be decided and monitored by a specialized doctor.<\/p>\n\n\n\n<p class=\"wp-block-paragraph\"><strong>15.<\/strong> In case of regression, it is also recommended to contact a specialized center for Kleefstra syndrome, both for the management of the condition and for the collection of more data.<\/p>\n\n\n\n<p class=\"has-text-align-center is-style-info wp-block-paragraph\">A sudden loss of speech, motor skills, self-care, or interest in the environment <strong>this should not be automatically attributed to the syndrome<\/strong>. Potential neurological, psychiatric, and physical causes must be investigated.<\/p>\n<\/div><\/details><\/div>\n\n\n\n<div class=\"wp-block-coblocks-accordion-item\"><details><summary class=\"wp-block-coblocks-accordion-item__title has-background\" style=\"background-color:#f4e8ff\">4. Neurological monitoring and epilepsy<\/summary><div class=\"wp-block-coblocks-accordion-item__content\" style=\"border-color:#f4e8ff\">\n<p class=\"wp-block-paragraph\">Epilepsy has been reported in about <strong>10%\u201344%<\/strong> of individuals with KLEFS1. The age of onset and the type of seizures vary significantly.<\/p>\n\n\n\n<h3 class=\"wp-block-heading\" style=\"font-size:18px\">Does everyone need a brain MRI?;<\/h3>\n\n\n\n<p class=\"wp-block-paragraph\"><strong>No.<\/strong><\/p>\n\n\n\n<p class=\"wp-block-paragraph\">Although brain imaging abnormalities have been described in several individuals, guidelines state that <strong>There is no indication for a brain MRI as a routine examination in every individual with Kleefstra syndrome.<\/strong>.<\/p>\n\n\n\n<h3 class=\"wp-block-heading recommendations-title\" style=\"font-size:18px\">The recommendations<\/h3>\n\n\n\n<p class=\"wp-block-paragraph\"><strong>16.<\/strong> Brain MRI should be examined when there are specific clinical indications, in particular:<\/p>\n\n\n\n<ul class=\"wp-block-list\">\n<li>focal seizures,<\/li>\n\n\n\n<li>focal findings on EEG,<\/li>\n\n\n\n<li>developmental regression\/loss of skills,<\/li>\n\n\n\n<li>acute onset of psychosis or catatonia.<\/li>\n<\/ul>\n\n\n\n<p class=\"wp-block-paragraph\"><strong>17.<\/strong> A repeat MRI may be needed when there are significant findings on the initial scan or when new clinical changes occur.<\/p>\n\n\n\n<h3 class=\"wp-block-heading\" style=\"font-size:18px\">Is an EEG needed for everyone?;<\/h3>\n\n\n\n<p class=\"wp-block-paragraph\">Also <strong>no<\/strong>.<\/p>\n\n\n\n<p class=\"wp-block-paragraph\"><strong>18.<\/strong> When there are episodes suspected to be epileptic seizures or a new diagnosis of epilepsy, a referral to a neurologist or epilepsy specialist should be made.<\/p>\n\n\n\n<p class=\"wp-block-paragraph\"><strong>19.<\/strong> EEG is recommended when:<\/p>\n\n\n\n<ul class=\"wp-block-list\">\n<li>there is a suspicion of seizures or epilepsy,<\/li>\n\n\n\n<li>or developmental regression appears.<\/li>\n<\/ul>\n\n\n\n<p class=\"wp-block-paragraph\">Ideally, the recording should include <strong>video, wakefulness, and sleep<\/strong>.<\/p>\n\n\n\n<p class=\"wp-block-paragraph\">A new EEG may be needed if the type of episodes changes or if the seizures increase significantly.<\/p>\n\n\n\n<p class=\"wp-block-paragraph\"><strong>20.<\/strong> The discontinuation of antiepileptic therapy must be done in accordance with standard neurological guidelines and on an individualized basis. In severe or difficult-to-control epilepsy, a longer duration of treatment may be necessary.<\/p>\n\n\n\n<hr class=\"wp-block-separator has-alpha-channel-opacity\"\/>\n<\/div><\/details><\/div>\n\n\n\n<div class=\"wp-block-coblocks-accordion-item\"><details><summary class=\"wp-block-coblocks-accordion-item__title has-background\" style=\"background-color:#f4e8ff\">5. Sleep<\/summary><div class=\"wp-block-coblocks-accordion-item__content\" style=\"border-color:#f4e8ff\">\n<p class=\"wp-block-paragraph\">Sleep disorders are particularly common. In the data combined for the guideline, they appear in approximately <strong>55% in individuals with KLEFS1<\/strong>.<\/p>\n\n\n\n<p class=\"wp-block-paragraph\">Difficulty initiating sleep and frequent or prolonged awakenings are reported most frequently. Sleep apnea occurs in a smaller percentage.<\/p>\n\n\n\n<p class=\"wp-block-paragraph\">Of particular importance is that <strong>A sudden and severe deterioration of sleep can in some cases precede a regression episode.<\/strong>.<\/p>\n\n\n\n<h3 class=\"wp-block-heading recommendations-title\" style=\"font-size:18px\">What do the guidelines suggest<\/h3>\n\n\n\n<p class=\"wp-block-paragraph\"><strong>21.<\/strong> Sleep should be discussed and evaluated <strong>regularly at all ages<\/strong>. Practical tools, such as a sleep diary, can be used.<\/p>\n\n\n\n<p class=\"wp-block-paragraph\"><strong>22.<\/strong> Good sleep hygiene and adjustment of the daily and evening routine to the individual's sensory needs are recommended.<\/p>\n\n\n\n<p class=\"wp-block-paragraph\"><strong>23.<\/strong> When there is a sleep problem, potential ones must be investigated:<\/p>\n\n\n\n<ul class=\"wp-block-list\">\n<li>physical,<\/li>\n\n\n\n<li>psychiatric,<\/li>\n\n\n\n<li>social,<\/li>\n\n\n\n<li>environmental<\/li>\n<\/ul>\n\n\n\n<p class=\"wp-block-paragraph\">Factors.<\/p>\n\n\n\n<p class=\"wp-block-paragraph\">For example, constipation, gastroesophageal reflux, sleep apnea, anxiety, or another mental disorder can coexist.<\/p>\n\n\n\n<p class=\"wp-block-paragraph\"><strong>24.<\/strong> When persistently poor sleep is reported, early referral to a sleep specialist should be considered.<\/p>\n\n\n\n<p class=\"wp-block-paragraph\"><strong>25.<\/strong> Families and professionals need to know that have been described <strong>paradoxical reactions to medications used for sleep<\/strong>, including benzodiazepines and in some cases melatonin. Their use without professional guidance is discouraged.<\/p>\n\n\n\n<p class=\"wp-block-paragraph\"><strong>26.<\/strong> From adolescence onwards, a <strong>acute and severe change in sleep pattern<\/strong> It must be handled with special care and also evaluated as a potential early regression element.<\/p>\n<\/div><\/details><\/div>\n\n\n\n<div class=\"wp-block-coblocks-accordion-item\"><details><summary class=\"wp-block-coblocks-accordion-item__title has-background\" style=\"background-color:#f4e8ff\">6. Hearing<\/summary><div class=\"wp-block-coblocks-accordion-item__content\" style=\"border-color:#f4e8ff\">\n<p class=\"wp-block-paragraph\">It may be a conductive, sensorineural, or mixed hearing loss. Frequent ear infections and cerumen accumulation can also worsen hearing.<\/p>\n\n\n\n<h3 class=\"wp-block-heading recommendations-title\" style=\"font-size:18px\">What do the guidelines suggest<\/h3>\n\n\n\n<p class=\"wp-block-paragraph\"><strong>27. Audiological examination:<\/strong><\/p>\n\n\n\n<ul class=\"wp-block-list\">\n<li>during diagnosis,<\/li>\n\n\n\n<li><strong>every year up to the age of 6 years<\/strong>,<\/li>\n\n\n\n<li>then <strong>every two years until early puberty<\/strong>.<\/li>\n<\/ul>\n\n\n\n<p class=\"wp-block-paragraph\">Testing can be done more frequently if there are symptoms or concern from the family.<\/p>\n\n\n\n<p class=\"wp-block-paragraph\">Potential disturbances must also be taken into account <strong>central auditory processing<\/strong>.<\/p>\n\n\n\n<p class=\"wp-block-paragraph\"><strong>28.<\/strong> In adults, hearing should be monitored according to the recommendations for individuals with intellectual disabilities.<\/p>\n\n\n\n<p class=\"wp-block-paragraph\"><strong>29.<\/strong> Excessive earwax buildup must be prevented.<\/p>\n\n\n\n<p class=\"wp-block-paragraph\"><strong>30.<\/strong> Otitis media and fluid in the middle ear must be treated promptly, especially during critical speech development ages.<\/p>\n\n\n\n<p class=\"wp-block-paragraph\"><strong>31.<\/strong> Interventions for hearing and vision must be customized:<\/p>\n\n\n\n<ul class=\"wp-block-list\">\n<li>in developmental age,<\/li>\n\n\n\n<li>to the degree of sensory difficulty,<\/li>\n\n\n\n<li>in behavior,<\/li>\n\n\n\n<li>in sensory processing disorders,<\/li>\n\n\n\n<li>and to potential touch intolerance or examinations.<\/li>\n<\/ul>\n<\/div><\/details><\/div>\n\n\n\n<div class=\"wp-block-coblocks-accordion-item\"><details><summary class=\"wp-block-coblocks-accordion-item__title has-background\" style=\"background-color:#f4e8ff\">7. Vision<\/summary><div class=\"wp-block-coblocks-accordion-item__content\" style=\"border-color:#f4e8ff\">\n<p class=\"wp-block-paragraph\">In Kleefstra syndrome, refractive errors, particularly hyperopia, as well as strabismus, are frequently observed.<\/p>\n\n\n\n<p class=\"wp-block-paragraph\">The new directive also highlights the importance of&nbsp;<strong>Cerebral Visual Impairment (CVI)<\/strong>, which may not be easy to identify.<\/p>\n\n\n\n<h3 class=\"wp-block-heading recommendations-title\" style=\"font-size:18px\">The recommendations<\/h3>\n\n\n\n<p class=\"wp-block-paragraph\"><strong>32.<\/strong>&nbsp;An ophthalmological evaluation should be performed&nbsp;<strong>during diagnosis<\/strong>&nbsp;and whenever the individual or family expresses concerns.<\/p>\n\n\n\n<p class=\"wp-block-paragraph\">Special attention is needed for:<\/p>\n\n\n\n<ul class=\"wp-block-list\">\n<li>strabismus,<\/li>\n\n\n\n<li>refractive errors and especially hyperopia,<\/li>\n\n\n\n<li>probable CVI.<\/li>\n<\/ul>\n\n\n\n<p class=\"wp-block-paragraph\"><strong>33.<\/strong>&nbsp;Visual acuity should be checked regularly according to local protocols, with special attention to strabismus in children under 6 years of age.<\/p>\n\n\n\n<p class=\"wp-block-paragraph\"><strong>34.<\/strong>&nbsp;When there are vision problems, they must be addressed appropriately and, if necessary, low vision rehabilitation specialists, occupational therapists, or other professionals who can suggest adjustments and assistive technologies should be involved.<\/p>\n<\/div><\/details><\/div>\n\n\n\n<div class=\"wp-block-coblocks-accordion-item\"><details><summary class=\"wp-block-coblocks-accordion-item__title has-background\" style=\"background-color:#f4e8ff\">8. Speech, language, and communication<\/summary><div class=\"wp-block-coblocks-accordion-item__content\" style=\"border-color:#f4e8ff\">\n<p class=\"wp-block-paragraph\">Communication is one of the most important areas of support at KLEFS1.<\/p>\n\n\n\n<p class=\"wp-block-paragraph\">Capabilities vary greatly between individuals. According to the data reviewed for the directive, approximately <strong>65% of individuals aged 3 and older were able to form sentences<\/strong>, while nearly all of the verbal participants in the relevant studies exhibited some form of speech disorder.<\/p>\n\n\n\n<h3 class=\"wp-block-heading recommendations-title\" style=\"font-size:18px\">What do the guidelines suggest<\/h3>\n\n\n\n<p class=\"wp-block-paragraph\"><strong>35.<\/strong> Speech and language assessment must be conducted:<\/p>\n\n\n\n<ul class=\"wp-block-list\">\n<li>during diagnosis,<\/li>\n\n\n\n<li>and <strong>at least once a year until the age of 12<\/strong>.<\/li>\n<\/ul>\n\n\n\n<p class=\"wp-block-paragraph\"><strong>36.<\/strong> During adolescence and adulthood, the evaluation is repeated as needed, e.g., in the event of a new concern or following an episode of regression.<\/p>\n\n\n\n<p class=\"wp-block-paragraph\"><strong>37.<\/strong> When speech does not cover all daily communication needs, an assessment must be made for <strong>Augmentative and Alternative Communication (AAC).<\/strong><\/p>\n\n\n\n<p class=\"wp-block-paragraph\"><strong>38.<\/strong> The therapeutic intervention must be tailored to the specific speech and language profile and may include:<\/p>\n\n\n\n<ul class=\"wp-block-list\">\n<li>speech therapy,<\/li>\n\n\n\n<li>AAC,<\/li>\n\n\n\n<li>Meanings,<\/li>\n\n\n\n<li>Gestures,<\/li>\n\n\n\n<li>other appropriate forms of communication.<\/li>\n<\/ul>\n\n\n\n<p class=\"wp-block-paragraph\"><strong>39.<\/strong> The AAC system must be adapted to each individual's cognitive, visual, auditory, and sensory capabilities, as well as any co-occurring neurodevelopmental conditions.<\/p>\n\n\n\n<p class=\"has-text-align-center is-style-info wp-block-paragraph\">The guidelines clearly state that AAC <strong>it does not hinder speech development<\/strong>. On the contrary, it can offer a child or an adult an effectiv<\/p>\n<\/div><\/details><\/div>\n\n\n\n<div class=\"wp-block-coblocks-accordion-item\"><details><summary class=\"wp-block-coblocks-accordion-item__title has-background\" style=\"background-color:#f4e8ff\">9. Heart<\/summary><div class=\"wp-block-coblocks-accordion-item__content\" style=\"border-color:#f4e8ff\">\n<p class=\"wp-block-paragraph\">Kleefstra syndrome can be accompanied by congenital heart disease as well as heart rhythm disorders, which appear to require special attention from adolescence and adulthood.<\/p>\n\n\n\n<h3 class=\"wp-block-heading recommendations-title\" style=\"font-size:18px\">What do the guidelines suggest<\/h3>\n\n\n\n<p class=\"wp-block-paragraph\"><strong>40.<\/strong> During diagnosis, it must be performed <strong>cardiological evaluation<\/strong>, which includes:<\/p>\n\n\n\n<ul class=\"wp-block-list\">\n<li>echocardiogram \u2014 or cardiac MRI where indicated and available \u2014 to check for anatomical problems,<\/li>\n\n\n\n<li>and an electrocardiogram (ECG) for rhythm disorders.<\/li>\n<\/ul>\n\n\n\n<p class=\"wp-block-paragraph\"><strong>41.<\/strong> When starting a new medication with potential cardiac effects \u2014 for example, certain psychiatric, neurological, or prokinetic drugs \u2014 consultation with a cardiologist is recommended.<\/p>\n\n\n\n<p class=\"wp-block-paragraph\"><strong>42.<\/strong> Any underlying heart conditions or arrhythmias are treated in accordance with standard cardiology protocols.<\/p>\n\n\n\n<p class=\"wp-block-paragraph\"><strong>43.<\/strong> The guidelines recommend a low threshold for performing an ECG, and, <strong>from the age of 18, an ECG every year in all individuals with KLEFS1<\/strong>.<\/p>\n\n\n\n<p class=\"wp-block-paragraph\"><strong>44.<\/strong> Abnormal ECG or new\/worsening cardiorespiratory symptoms require immediate cardiological evaluation.<\/p>\n\n\n\n<p class=\"wp-block-paragraph\"><strong>45.<\/strong> In the event of new cardiorespiratory symptoms or even an unexplained worsening of cognitive function, mood, or overall functioning, repeat cardiac imaging, an ECG, or a prolonged heart rhythm recording.<\/p>\n<\/div><\/details><\/div>\n\n\n\n<div class=\"wp-block-coblocks-accordion-item\"><details><summary class=\"wp-block-coblocks-accordion-item__title has-background\" style=\"background-color:#f4e8ff\">10. Growth, weight, and metabolic health<\/summary><div class=\"wp-block-coblocks-accordion-item__content\" style=\"border-color:#f4e8ff\">\n<p class=\"wp-block-paragraph\">KLEFS1 has been associated with short stature in a subset of individuals, smaller head circumference, and particularly with <strong>increased risk of being overweight and obese<\/strong>.<\/p>\n\n\n\n<p class=\"wp-block-paragraph\">Monitoring weight and metabolic health becomes particularly important as age increases.<\/p>\n\n\n\n<h3 class=\"wp-block-heading recommendations-title\" style=\"font-size:18px\">The recommendations<\/h3>\n\n\n\n<p class=\"wp-block-paragraph\"><strong>46. In childhood and adolescence:<\/strong><\/p>\n\n\n\n<ul class=\"wp-block-list\">\n<li>routine measurement of height and weight,<\/li>\n\n\n\n<li>evaluation using appropriate growth charts,<\/li>\n\n\n\n<li>head circumference measurement at least up to the age of 3 years.<\/li>\n<\/ul>\n\n\n\n<p class=\"wp-block-paragraph\"><strong>In adult life:<\/strong><\/p>\n\n\n\n<ul class=\"wp-block-list\">\n<li>weight,<\/li>\n\n\n\n<li>waist circumference,<\/li>\n\n\n\n<li>BMI,<\/li>\n<\/ul>\n\n\n\n<p class=\"wp-block-paragraph\">they must be evaluated <strong>at least once a year<\/strong> or more frequently if there is a clinical indication.<\/p>\n\n\n\n<p class=\"wp-block-paragraph\"><strong>47.<\/strong> In short stature or overweight\/obesity, potential treatable causes should be investigated according to standard medical guidelines, such as thyroid disorders or other endocrinological causes.<\/p>\n\n\n\n<p class=\"wp-block-paragraph\"><strong>48.<\/strong> Efforts should be made to encourage:<\/p>\n\n\n\n<ul class=\"wp-block-list\">\n<li>regular physical activity,<\/li>\n\n\n\n<li>balanced diet,<\/li>\n\n\n\n<li>and, where necessary, cooperation with a dietitian or nutritionist.<\/li>\n<\/ul>\n\n\n\n<p class=\"wp-block-paragraph\">This is particularly important when obesity is already present or when psychotropic medications that can increase weight are used.<\/p>\n\n\n\n<p class=\"wp-block-paragraph\"><strong>49.<\/strong> Its operation <strong>thyroid<\/strong> it must be evaluated at least at the onset of puberty and when there are relevant indications.<\/p>\n\n\n\n<p class=\"wp-block-paragraph\">Adolescents and adults should also be monitored for prediabetes or diabetes according to standard protocols.<\/p>\n\n\n\n<p class=\"wp-block-paragraph\"><strong>50.<\/strong> Health and bone density should be examined at the onset of puberty and when there are multiple or unexplained fractures. The guideline also states that a vitamin D supplement may be considered, particularly when sun exposure is limited.<\/p>\n<\/div><\/details><\/div>\n\n\n\n<div class=\"wp-block-coblocks-accordion-item\"><details><summary class=\"wp-block-coblocks-accordion-item__title has-background\" style=\"background-color:#f4e8ff\">11. Constipation<\/summary><div class=\"wp-block-coblocks-accordion-item__content\" style=\"border-color:#f4e8ff\">\n<p class=\"wp-block-paragraph\">In the new guidelines, constipation is not treated as a secondary or minor symptom.<\/p>\n\n\n\n<p class=\"wp-block-paragraph\">It appears around&nbsp;<strong>half people with KLEFS1<\/strong>&nbsp;and it can exist at any age. In some individuals it can be severe and affect sleep, behavior, mental state, and quality of life.<\/p>\n\n\n\n<h3 class=\"wp-block-heading recommendations-title\" style=\"font-size:18px\">The recommendations<\/h3>\n\n\n\n<p class=\"wp-block-paragraph\"><strong>51.<\/strong>&nbsp;The probability of constipation should be evaluated&nbsp;<strong>at all ages<\/strong>, with an appropriate medical history and physical examination and, when necessary, a more specific examination.<\/p>\n\n\n\n<p class=\"wp-block-paragraph\"><strong>52.<\/strong>&nbsp;Healthcare professionals should actively inquire about the onset or worsening of constipation, even when it presents in an unusual manner.<\/p>\n\n\n\n<p class=\"wp-block-paragraph\">This is especially important when there is simultaneously:<\/p>\n\n\n\n<ul class=\"wp-block-list\">\n<li>behavioral deterioration,<\/li>\n\n\n\n<li>sleep problems,<\/li>\n\n\n\n<li>or a change in mental state.<\/li>\n<\/ul>\n\n\n\n<p class=\"wp-block-paragraph\"><strong>53.<\/strong>&nbsp;When there are concerning signs, other possible causes must be sought. The guideline mentions, among other things, checking&nbsp;<strong>TSH and fT4<\/strong>&nbsp;for thyroid function.<\/p>\n\n\n\n<p class=\"wp-block-paragraph\"><strong>54.<\/strong>&nbsp;For prevention and treatment, where appropriate, the following are recommended:<\/p>\n\n\n\n<ul class=\"wp-block-list\">\n<li>adequate fluids,<\/li>\n\n\n\n<li>dietary fiber,<\/li>\n\n\n\n<li>physical activity,<\/li>\n\n\n\n<li>healthy toilet habits.<\/li>\n<\/ul>\n\n\n\n<p class=\"wp-block-paragraph\"><strong>55.<\/strong>&nbsp;The pharmacological treatment of constipation should follow standard protocols, taking special consideration of any risk of aspiration.<\/p>\n\n\n\n<p class=\"wp-block-paragraph\"><strong>56.<\/strong>&nbsp;If constipation persists despite systematic treatment, referral to a gastroenterologist is recommended.<\/p>\n<\/div><\/details><\/div>\n\n\n\n<div class=\"wp-block-coblocks-accordion-item\"><details><summary class=\"wp-block-coblocks-accordion-item__title has-background\" style=\"background-color:#f4e8ff\">12. Support for the individual and the family<\/summary><div class=\"wp-block-coblocks-accordion-item__content\" style=\"border-color:#f4e8ff\">\n<p class=\"wp-block-paragraph\">A particularly important feature of the new guidelines is that care&nbsp;<strong>is not limited to medical examinations<\/strong>.<\/p>\n\n\n\n<p class=\"wp-block-paragraph\">The last ten recommendations directly concern the family, information, psychological support, access to services, and the continuity of care.<\/p>\n\n\n\n<h3 class=\"wp-block-heading recommendations-title\" style=\"font-size:18px\">The recommendations<\/h3>\n\n\n\n<p class=\"wp-block-paragraph\"><strong>57.<\/strong>&nbsp;Following the diagnosis, timely, clear, honest, and understandable information must be provided regarding:<\/p>\n\n\n\n<ul class=\"wp-block-list\">\n<li>the cause of the syndrome,<\/li>\n\n\n\n<li>the appropriate examinations and monitoring,<\/li>\n\n\n\n<li>and the natural course of the condition.<\/li>\n<\/ul>\n\n\n\n<p class=\"wp-block-paragraph\"><strong>58.<\/strong>&nbsp;Information must be tailored to the needs, concerns, preferences, and management capabilities of each family.<\/p>\n\n\n\n<p class=\"wp-block-paragraph\">Follow-up appointments must be offered so that there is the opportunity to discuss new questions that arise over time.<\/p>\n\n\n\n<p class=\"wp-block-paragraph\"><strong>59.<\/strong>&nbsp;Families must receive information about:<\/p>\n\n\n\n<ul class=\"wp-block-list\">\n<li>patient organizations,<\/li>\n\n\n\n<li>mutual support groups,<\/li>\n\n\n\n<li>consulting services,<\/li>\n\n\n\n<li>and reliable sources of information.<\/li>\n<\/ul>\n\n\n\n<p class=\"wp-block-paragraph\"><strong>60.<\/strong>&nbsp;The emotional well-being of the individual and the family must be investigated&nbsp;<strong>at every contact with health services<\/strong>.<\/p>\n\n\n\n<p class=\"wp-block-paragraph\">The directive explicitly mentions not only the parents but also&nbsp;<strong>siblings and grandparents<\/strong>.<\/p>\n\n\n\n<p class=\"wp-block-paragraph\"><strong>61.<\/strong>&nbsp;Healthcare professionals must, when necessary, seek advice from experts and specialized Kleefstra centers.<\/p>\n\n\n\n<p class=\"wp-block-paragraph\"><strong>62.<\/strong>&nbsp;Professionals must be open to the information brought to the appointment by the individual themselves, their family, or the people supporting them.<\/p>\n\n\n\n<p class=\"wp-block-paragraph\">This constitutes a particularly important recognition of&nbsp;<strong>empirical knowledge of families<\/strong>&nbsp;in such a rare syndrome.<\/p>\n\n\n\n<p class=\"wp-block-paragraph\"><strong>63.<\/strong>&nbsp;Families should, where possible, be informed about opportunities to participate in:<\/p>\n\n\n\n<ul class=\"wp-block-list\">\n<li>patient registries,<\/li>\n\n\n\n<li>research databases,<\/li>\n\n\n\n<li>and longitudinal studies on the course of the syndrome (<em>natural history studies<\/em>).<\/li>\n<\/ul>\n\n\n\n<p class=\"wp-block-paragraph\"><strong>64.<\/strong>&nbsp;They must be supported to access available services, such as:<\/p>\n\n\n\n<ul class=\"wp-block-list\">\n<li>financial support,<\/li>\n\n\n\n<li>educational resources,<\/li>\n\n\n\n<li>disability services,<\/li>\n\n\n\n<li>respite care services for caregivers<em>respite care<\/em>).<\/li>\n<\/ul>\n\n\n\n<p class=\"wp-block-paragraph\"><strong>65.<\/strong>&nbsp;The planning of the transition from pediatric to adult services should begin&nbsp;<strong>preventatively since the middle of adolescence<\/strong>.<\/p>\n\n\n\n<p class=\"wp-block-paragraph\"><strong>66.<\/strong>&nbsp;Where possible, individuals with Kleefstra and their families should be connected with&nbsp;<strong>interdisciplinary team or specialized clinic and\/or a care coordinator<\/strong>.<\/p>\n<\/div><\/details><\/div>\n\n\n\n<div class=\"wp-block-coblocks-accordion-item\"><details><summary class=\"wp-block-coblocks-accordion-item__title has-background\" style=\"background-color:#f4e8ff\">13. Practical monitoring checklist<\/summary><div class=\"wp-block-coblocks-accordion-item__content\" style=\"border-color:#f4e8ff\">\n<p class=\"wp-block-paragraph\">The 66 recommendations can be summarized into a simpler practical framework.<\/p>\n\n\n\n<h3 class=\"wp-block-heading\" style=\"font-size:18px\">During diagnosis<\/h3>\n\n\n\n<p class=\"wp-block-paragraph\">To be examined or organized, as the case may be:<\/p>\n\n\n\n<ul class=\"wp-block-list\">\n<li>clinical genetics and genetic counseling,<\/li>\n\n\n\n<li>Behavioral and mental health assessment,<\/li>\n\n\n\n<li>cardiological examination with echocardiogram and ECG,<\/li>\n\n\n\n<li>audiological assessment,<\/li>\n\n\n\n<li>eye examination,<\/li>\n\n\n\n<li>speech, language and communication assessment,<\/li>\n\n\n\n<li>growth and nutrition assessment,<\/li>\n\n\n\n<li>screening for constipation and other current problems,<\/li>\n\n\n\n<li>sleep evaluation.<\/li>\n<\/ul>\n\n\n\n<p class=\"wp-block-paragraph\"><strong>Brain MRI and EEG are not automatically required due to the diagnosis<\/strong>- they are performed when there are relevant clinical indications.<\/p>\n\n\n\n<hr class=\"wp-block-separator has-alpha-channel-opacity\"\/>\n\n\n\n<h3 class=\"wp-block-heading\" style=\"font-size:18px\">During childhood<\/h3>\n\n\n\n<p class=\"wp-block-paragraph\">Particular emphasis is needed on:<\/p>\n\n\n\n<ul class=\"wp-block-list\">\n<li>development and motor skills,<\/li>\n\n\n\n<li>speech and communication,<\/li>\n\n\n\n<li>AAC when needed,<\/li>\n\n\n\n<li>Hearing,<\/li>\n\n\n\n<li>Vision,<\/li>\n\n\n\n<li>Sleep,<\/li>\n\n\n\n<li>Behavior,<\/li>\n\n\n\n<li>Constipation,<\/li>\n\n\n\n<li>height and weight.<\/li>\n<\/ul>\n\n\n\n<h3 class=\"wp-block-heading\" style=\"font-size:18px\">Specific frequencies mentioned in the instructions<\/h3>\n\n\n\n<p class=\"wp-block-paragraph\"><strong>Language:<\/strong> At least one annual evaluation until the age of 12.<\/p>\n\n\n\n<p class=\"wp-block-paragraph\"><strong>Hearing:<\/strong> annually until age 6, and then every two years until early adolescence.<\/p>\n\n\n\n<p class=\"wp-block-paragraph\"><strong>Head circumference:<\/strong> on a regular basis, at least until the age of 3.<\/p>\n\n\n\n<p class=\"wp-block-paragraph\"><strong>Behavior\/Mental Health:<\/strong> at least once a year.<\/p>\n\n\n\n<hr class=\"wp-block-separator has-alpha-channel-opacity\"\/>\n\n\n\n<h3 class=\"wp-block-heading\" style=\"font-size:18px\">During adolescence<\/h3>\n\n\n\n<p class=\"wp-block-paragraph\">Adolescence is a period during which increased attention is required to:<\/p>\n\n\n\n<ul class=\"wp-block-list\">\n<li>significant changes in sleep,<\/li>\n\n\n\n<li>new psychiatric or behavioral symptoms,<\/li>\n\n\n\n<li>loss of skills,<\/li>\n\n\n\n<li>weight and metabolic health,<\/li>\n\n\n\n<li>thyroid,<\/li>\n\n\n\n<li>bone health,<\/li>\n\n\n\n<li>and planning the transition to adult services.<\/li>\n<\/ul>\n\n\n\n<p class=\"wp-block-paragraph\">Sudden, severe insomnia following the onset of puberty should not be treated simply as a \u00absleep problem,\u00bb as it has been observed in some individuals prior to an episode of regression.<\/p>\n\n\n\n<hr class=\"wp-block-separator has-alpha-channel-opacity\"\/>\n\n\n\n<h4 class=\"wp-block-heading\" style=\"font-size:18px\">In adulthood<\/h4>\n\n\n\n<p class=\"wp-block-paragraph\">The monitoring <strong>it doesn&#x27;t end when childhood is over<\/strong>.<\/p>\n\n\n\n<p class=\"wp-block-paragraph\">The guidelines place special emphasis on:<\/p>\n\n\n\n<ul class=\"wp-block-list\">\n<li>mental health,<\/li>\n\n\n\n<li>the potential loss of skills,<\/li>\n\n\n\n<li>in one&#x27;s sleep,<\/li>\n\n\n\n<li>in communication,<\/li>\n\n\n\n<li>heart health,<\/li>\n\n\n\n<li>on weight and metabolism,<\/li>\n\n\n\n<li>in constipation,<\/li>\n\n\n\n<li>hearing and vision,<\/li>\n\n\n\n<li>and in maintaining functionality and quality of life.<\/li>\n<\/ul>\n\n\n\n<p class=\"wp-block-paragraph\">From the <strong>18 years and older, annual ECG is recommended<\/strong> to monitor heart rhythm disorders.<\/p>\n\n\n\n<p class=\"wp-block-paragraph\">In adults, at least an annual assessment of weight, BMI, and waist circumference is also recommended.<\/p>\n\n\n\n<hr class=\"wp-block-separator has-alpha-channel-opacity\"\/>\n\n\n\n<h3 class=\"wp-block-heading\" style=\"font-size:18px\">When is a more immediate medical evaluation needed?;<\/h3>\n\n\n\n<p class=\"wp-block-paragraph\">Special attention is needed when a new or significant change occurs, such as:<\/p>\n\n\n\n<ul class=\"wp-block-list\">\n<li>loss of skills already acquired,<\/li>\n\n\n\n<li>sudden significant reduction in speech or communication,<\/li>\n\n\n\n<li>a significant change in mobility or self-care,<\/li>\n\n\n\n<li>acute and severe insomnia,<\/li>\n\n\n\n<li>sudden significant change in behavior or mental state,<\/li>\n\n\n\n<li>potential epileptic seizures or a significant change in previously known epilepsy,<\/li>\n\n\n\n<li>new cardiopulmonary symptoms,<\/li>\n\n\n\n<li>severe or persistent constipation.<\/li>\n<\/ul>\n\n\n\n<p class=\"has-text-align-center is-style-info wp-block-paragraph\">The guidelines repeatedly emphasize that <strong>The new changes should not automatically be considered part of Kleefstra without investigation.<\/strong>.<\/p>\n<\/div><\/details><\/div>\n<\/div>\n\n\n\n<hr class=\"wp-block-separator has-alpha-channel-opacity\"\/>\n\n\n\n<div class=\"wp-block-columns is-layout-flex wp-container-core-columns-is-layout-8f761849 wp-block-columns-is-layout-flex\">\n<div class=\"wp-block-column is-style-default is-layout-flow wp-block-column-is-layout-flow\">\n<div class=\"wp-block-group\"><div class=\"wp-block-group__inner-container is-layout-constrained wp-block-group-is-layout-constrained\">\n<div class=\"wp-block-group guideline-card\"><div class=\"wp-block-group__inner-container is-layout-constrained wp-block-group-is-layout-constrained\">\n<h2 class=\"wp-block-heading has-text-align-center guideline-card has-text-color has-background has-link-color wp-elements-4\" style=\"color:#006d60;background-color:#e7fff594;font-size:20px\">What do these guidelines actually change in practice?;<\/h2>\n\n\n\n<div class=\"wp-block-group\"><div class=\"wp-block-group__inner-container is-layout-constrained wp-block-group-is-layout-constrained\">\n<div class=\"wp-block-group guideline-card\"><div class=\"wp-block-group__inner-container is-layout-constrained wp-block-group-is-layout-constrained\">\n<p class=\"wp-block-paragraph\">The most important change is not that a specific new examination is proposed. It is that for the first time Kleefstra syndrome is addressed through a <strong>organized, lifelong care model<\/strong>. Monitoring is no longer limited only to developmental delay or genetic diagnosis. Issues that families have been reporting for years are now officially recognized, such as:<\/p>\n\n\n\n<ul class=\"wp-block-list\">\n<li>severe sleep disorders,<\/li>\n\n\n\n<li>the loss of skills,<\/li>\n\n\n\n<li>changes in mental health,<\/li>\n\n\n\n<li>constipation,<\/li>\n\n\n\n<li>the need for alternative communication,<\/li>\n\n\n\n<li>difficulties in adult life,<\/li>\n\n\n\n<li>and the burden on the entire family.<\/li>\n<\/ul>\n\n\n\n<p class=\"wp-block-paragraph\">At the same time, the guidelines also attempt to prevent <strong>excessive testing without clinical indication<\/strong>. A person with Kleefstra does not need every possible test simply because they have the diagnosis. Monitoring must be organized yet individualized.<\/p>\n<\/div><\/div>\n<\/div><\/div>\n<\/div><\/div>\n<\/div><\/div>\n\n\n\n<p class=\"wp-block-paragraph\"><\/p>\n<\/div>\n\n\n\n<div class=\"wp-block-column is-layout-flow wp-block-column-is-layout-flow\">\n<div class=\"wp-block-group\"><div class=\"wp-block-group__inner-container is-layout-constrained wp-block-group-is-layout-constrained\">\n<div class=\"wp-block-group guideline-card\"><div class=\"wp-block-group__inner-container is-layout-constrained wp-block-group-is-layout-constrained\">\n<h2 class=\"wp-block-heading has-text-align-center guideline-card has-text-color has-background has-link-color wp-elements-5\" style=\"color:#080087;background-color:#def1ff;font-size:20px\">The family as part of the care team<\/h2>\n\n\n\n<div class=\"wp-block-group\"><div class=\"wp-block-group__inner-container is-layout-constrained wp-block-group-is-layout-constrained\">\n<div class=\"wp-block-group guideline-card\"><div class=\"wp-block-group__inner-container is-layout-constrained wp-block-group-is-layout-constrained\">\n<p class=\"wp-block-paragraph\">One of the most important messages of the document is that the family is not treated merely as a recipient of instructions. The experience of parents and caregivers is considered an important source of information. Health professionals are asked:<\/p>\n\n\n\n<ul class=\"wp-block-list\">\n<li>to listen to the family's comments,<\/li>\n\n\n\n<li>to take seriously the changes that the family observes,<\/li>\n\n\n\n<li>to provide clear and honest information,<\/li>\n\n\n\n<li>to recognize uncertainty when it exists,<\/li>\n\n\n\n<li>and to return to the discussion as the child grows and needs change.<\/li>\n<\/ul>\n\n\n\n<p class=\"wp-block-paragraph\">The guidelines also point out that caring for a person with a rare genetic condition can affect the mental and emotional health of the entire family, and that support should involve, where needed, parents, siblings, and grandparents.<\/p>\n<\/div><\/div>\n<\/div><\/div>\n<\/div><\/div>\n<\/div><\/div>\n<\/div>\n\n\n\n<div class=\"wp-block-column is-layout-flow wp-block-column-is-layout-flow\">\n<div class=\"wp-block-group\"><div class=\"wp-block-group__inner-container is-layout-constrained wp-block-group-is-layout-constrained\">\n<div class=\"wp-block-group guideline-card\"><div class=\"wp-block-group__inner-container is-layout-constrained wp-block-group-is-layout-constrained\">\n<h2 class=\"wp-block-heading has-text-align-center guideline-card has-text-color has-background has-link-color wp-elements-6\" style=\"color:#b6721a;background-color:#fff8e794;font-size:20px\">Participate in the survey<\/h2>\n\n\n\n<div class=\"wp-block-group\"><div class=\"wp-block-group__inner-container is-layout-constrained wp-block-group-is-layout-constrained\">\n<div class=\"wp-block-group guideline-card\"><div class=\"wp-block-group__inner-container is-layout-constrained wp-block-group-is-layout-constrained\">\n<p class=\"wp-block-paragraph\">The new guidelines also recognize the importance of family involvement in research. Where possible, it is recommended that they be informed about:<\/p>\n\n\n\n<ul class=\"wp-block-list\">\n<li>Kleefstra syndrome patient registries,<\/li>\n\n\n\n<li>clinical data collection studies,<\/li>\n\n\n\n<li>and longitudinal studies of the progression of the syndrome.<\/li>\n<\/ul>\n\n\n\n<p class=\"wp-block-paragraph\">Such studies help us better understand how KLEFS1 changes with age and to create appropriate tools for future clinical trials.<\/p>\n<\/div><\/div>\n<\/div><\/div>\n<\/div><\/div>\n<\/div><\/div>\n<\/div>\n<\/div>\n\n\n\n<hr class=\"wp-block-separator has-alpha-channel-opacity\"\/>\n\n\n\n<div class=\"wp-block-group\"><div class=\"wp-block-group__inner-container is-layout-constrained wp-block-group-is-layout-constrained\">\n<p class=\"wp-block-paragraph\"><\/p>\n\n\n\n<h3 class=\"wp-block-heading has-text-color has-link-color wp-elements-7\" style=\"color:#8b1aba;font-size:18px\">What these instructions are not<\/h3>\n\n\n\n<p class=\"wp-block-paragraph\">The guidelines:<\/p>\n\n\n\n<ul class=\"wp-block-list\">\n<li><strong>do not mean that every person with Kleefstra will present all the mentioned problems,<\/strong><\/li>\n\n\n\n<li>do not predict the progress of a specific child,<\/li>\n\n\n\n<li>do not replace clinical judgment,<\/li>\n\n\n\n<li>do not constitute a personalized treatment plan,<\/li>\n\n\n\n<li>and do not indicate that every test must be performed on every individual.<\/li>\n<\/ul>\n\n\n\n<p class=\"wp-block-paragraph\">KLEFS1 is characterized by high clinical heterogeneity. Monitoring must always be tailored to the age, genetic finding, clinical picture, needs, and capabilities of the specific individual.<\/p>\n<\/div><\/div>\n\n\n\n<hr class=\"wp-block-separator has-alpha-channel-opacity\"\/>\n\n\n\n<h3 class=\"wp-block-heading has-text-color has-link-color wp-elements-8\" style=\"color:#8b1aba;font-size:18px\">Will the instructions be updated again?;<\/h3>\n\n\n\n<p class=\"wp-block-paragraph\">Yes.<\/p>\n\n\n\n<p class=\"wp-block-paragraph\">The international team that developed the guidelines has anticipated <strong>their review every five years<\/strong>.<\/p>\n\n\n\n<p class=\"wp-block-paragraph\">If in the meantime there are new scientific data affecting any recommendation, a new systematic review will be conducted and the necessary changes will be proposed.<\/p>\n\n\n\n<p class=\"wp-block-paragraph\">This is particularly important for a field like Kleefstra, where knowledge about the natural history, biomarkers, and potential future therapeutic approaches is evolving rapidly.<\/p>\n\n\n\n<div class=\"wp-block-group\"><div class=\"wp-block-group__inner-container is-layout-constrained wp-block-group-is-layout-constrained\">\n<p class=\"is-style-info wp-block-paragraph\">The diagnosis of Kleefstra syndrome should not mean that a family is left alone to search for information or that every health professional follows a different approach. As of 2026, for the first time there is a <strong>internationally agreed care framework for KLEFS1<\/strong>. The 66 recommendations highlight that good care must be: <strong>lifelong, interdisciplinary, preventive, personalized and oriented towards both the individual and their family.<\/strong><\/p>\n\n\n\n<p class=\"is-style-info wp-block-paragraph\">And perhaps most importantly: when something changes \u2014 in sleep, behavior, communication, skills, or general functionality \u2014 <strong>The change is worth investigating and should not be simply attributed to the Kleefstra diagnosis.<\/strong><\/p>\n<\/div><\/div>\n\n\n\n<h3 class=\"wp-block-heading has-text-color has-link-color wp-elements-9\" style=\"color:#8b1aba;font-size:18px\">The full scientific guideline<\/h3>\n\n\n\n<p class=\"wp-block-paragraph\"><strong><a href=\"https:\/\/www.gimjournal.org\/action\/showPdf?pii=S1098-3600%2826%2900388-6\" target=\"_blank\" rel=\"noreferrer noopener\">Bouman A, Gaasterland CMW, Sloof-Enthoven C, et al.<\/a><\/strong><br><em>International clinical evidence-based guideline for Kleefstra syndrome.<\/em><br><strong>Genetics in Medicine. 2026;28:102070.<\/strong><br>DOI: 10.1016\/j.gim.2026.102070.<br>The directive was developed within the framework of international cooperation and <strong>European Reference Network for Intellectual Disability, TeleHealth, Autism and Congenital Anomalies (ERN ITHACA)<\/strong>.<\/p>\n\n\n\n<p class=\"wp-block-paragraph\"><em>Last update of this page: August 2026.<\/em><\/p>\n\n\n\n<p class=\"has-text-align-center study-significant wp-block-paragraph\">This page is an informative Greek presentation of international guidelines and not an official translation thereof. The information does not replace personalized medical advice or monitoring by appropriate healthcare professionals.<\/p>\n\n\n\n<p class=\"wp-block-paragraph\"><\/p>","protected":false},"excerpt":{"rendered":"<p>In 2026 the first international, documented clinical guidelines for Kleefstra type syndrome were published...<\/p>","protected":false},"author":1,"featured_media":0,"parent":0,"menu_order":0,"comment_status":"closed","ping_status":"closed","template":"","meta":{"_coblocks_attr":"","_coblocks_dimensions":"{\"coblocks-hero-71221453811\":{\"padding\":{}}}","_coblocks_responsive_height":"{\"coblocks-hero-71221453811\":{\"height\":{\"height\":500}}}","_coblocks_accordion_ie_support":"","footnotes":""},"class_list":["post-753","page","type-page","status-publish","hentry"],"yoast_head":"<!-- This site is optimized with the Yoast SEO plugin v28.6 - https:\/\/yoast.com\/product\/yoast-seo-wordpress\/ -->\n<title>\u0394\u03b9\u03b5\u03b8\u03bd\u03b5\u03af\u03c2 \u03ba\u03b1\u03c4\u03b5\u03c5\u03b8\u03c5\u03bd\u03c4\u03ae\u03c1\u03b9\u03b5\u03c2 \u03bf\u03b4\u03b7\u03b3\u03af\u03b5\u03c2 \u03b3\u03b9\u03b1 \u03c4\u03bf \u03c3\u03cd\u03bd\u03b4\u03c1\u03bf\u03bc\u03bf Kleefstra (2026) - 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