{"id":34,"date":"2026-05-07T10:44:30","date_gmt":"2026-05-07T10:44:30","guid":{"rendered":"https:\/\/hcp.biomarin.com\/en-us\/cln2\/?page_id=34"},"modified":"2026-09-15T13:54:13","modified_gmt":"2026-09-15T13:54:13","slug":"recognise-the-early-signs","status":"publish","type":"page","link":"https:\/\/hcp.biomarin.com\/en-us\/cln2\/identification-diagnosis\/recognise-the-early-signs\/","title":{"rendered":"Recognize the Early Signs"},"content":{"rendered":"<div id=\"acf-block-6a019df5cafb5\" class=\"simple-hero\">\n        <div class=\"wrapper\">\n\t\t<div class=\"inner-wrapper\">\n\t\t\t<div class=\"hero-content\">\n\t\t\t\t\t\t\t\t    <span class=\"section-title\">Identification &amp; Diagnosis<\/span>\n\t\t\t\t\t\t\t\t\t\t\t\t    <h1>Recognize the Early Signs\n<\/h1>\n\t\t\t\t\t\t\t<\/div>\n\t\t<\/div>\n\t<\/div>\n<\/div>\n\n<figure id=\"acf-block-6a019df5cb1c9\">\n    <div class=\"image image-align-left\">\n                    <img decoding=\"async\" class=\"\" src=\"https:\/\/hcp.biomarin.com\/en-us\/cln2\/wp-content\/uploads\/sites\/3\/2026\/05\/Identification-hero.jpg?v=0.4\" alt=\"\" \/>            <\/div>\n    <\/figure>\n\n<div id=\"acf-block-6a019df5cb376\" class=\"block wrapped-content block-tight-bottom\">\n    <div class=\"wrapper\">\n        <div class=\"inner-wrapper\">\n                \n<div id=\"acf-block-6a019df5cb4b4\" class=\"block-wysiwyg\">\n            \n\n<h2 style=\"font-weight: bold\">Expedite early diagnosis by recognizing the early hallmark symptoms of CLN2 disease<\/h2>\n<h4 style=\"color: #41b6e6\">New-onset, unprovoked seizures<\/h4>\n\n<ul class=\"no-left\">\n<li>Unprovoked seizures occur between the ages of 2 and 4 and are the symptom that most often leads parents\/caregivers to seek medical attention<sup>1,2<\/sup><\/li>\n<li>Initial new-onset, unprovoked seizures are commonly generalized tonic-clonic, myoclonic, or atonic<sup>2-4<\/sup>\n<ul class=\"sub_list\">\n<li>For some children, the first seizure can be febrile in nature<\/li>\n<\/ul>\n<\/li>\n<\/ul>\n\n    <\/div>\n        <\/div>\n    <\/div>\n<\/div>\n\n<div id=\"acf-block-6a019df5cb4f2\" class=\"block wrapped-content\">\n    <div class=\"wrapper\">\n        <div class=\"inner-wrapper\">\n                \n<figure id=\"acf-block-6a019df5cb530\">\n    <div class=\"image image-align-left\">\n                    <img decoding=\"async\" class=\"\" src=\"https:\/\/hcp.biomarin.com\/en-us\/cln2\/wp-content\/uploads\/sites\/3\/2026\/05\/hr-1900x2.png\" alt=\"\" \/>            <\/div>\n    <\/figure>\n        <\/div>\n    <\/div>\n<\/div>\n\n<div id=\"acf-block-6a019df5cb376\" class=\"block wrapped-content block-tight-bottom\">\n    <div class=\"wrapper\">\n        <div class=\"inner-wrapper\">\n                \n<div id=\"acf-block-6a019df5cb4b4\" class=\"block-wysiwyg\">\n            \n\n<h4 style=\"color: #41b6e6\">Early language delay<\/h4>\n\n<ul class=\"no-left\">\n<li>Language delay is one of the earliest symptoms to appear according to scientific findings<sup>5<\/sup><\/li>\n<\/ul>\n<h4 style=\"color: #41b6e6\">Percentage of \u201cLate Talkers\u201d in children with CLN2 disease vs age-matched controls (n=36)<sup>5<\/sup><\/h4>\n\n    <\/div>\n        <\/div>\n    <\/div>\n<\/div>\n\n<div id=\"acf-block-6a019df5cb4f2\" class=\"block wrapped-content block-tight-top\">\n    <div class=\"wrapper\">\n        <div class=\"inner-wrapper\">\n                \n<figure id=\"acf-block-6a019df5cb530\">\n    <div class=\"image image-natural-size image-align-center\">\n                    <img decoding=\"async\" class=\"\" src=\"https:\/\/hcp.biomarin.com\/en-us\/cln2\/wp-content\/uploads\/sites\/3\/2026\/05\/Signs-and-Symptoms-1.png?v=0.4\" alt=\"\" \/>            <\/div>\n    <\/figure>\n        <\/div>\n    <\/div>\n<\/div>\n\n<div id=\"acf-block-6a019df5cb376\" class=\"block wrapped-content\">\n    <div class=\"wrapper\">\n        <div class=\"inner-wrapper\">\n                \n<div id=\"acf-block-6a019df5cb4b4\" class=\"block-wysiwyg\">\n            <ul class=\"no-left\">\n<li>Delay in early language development was defined by the following criteria<sup>5<\/sup>:\n<ul class=\"sub_list\">\n<li>First single words acquired at 18 months (or later\/never)<\/li>\n<li>First two-word sentences at 24 months (or later\/never)<\/li>\n<li>First full sentences at 36 months (or later\/never)<\/li>\n<\/ul>\n<\/li>\n<li>In contrast, a separate study reported that only 27% of children (aged 3 to 5) who presented with unprovoked seizures had a history of language difficulties<sup>6<\/sup><\/li>\n<\/ul>\n    <\/div>\n        <\/div>\n    <\/div>\n<\/div>\n\n<div id=\"acf-block-6a019df5cb4f2\" class=\"block wrapped-content\">\n    <div class=\"wrapper\">\n        <div class=\"inner-wrapper\">\n                \n<figure id=\"acf-block-6a019df5cb530\">\n    <div class=\"image image-align-left\">\n                    <img decoding=\"async\" class=\"\" src=\"https:\/\/hcp.biomarin.com\/en-us\/cln2\/wp-content\/uploads\/sites\/3\/2026\/05\/hr-1900x2.png\" alt=\"\" \/>            <\/div>\n    <\/figure>\n        <\/div>\n    <\/div>\n<\/div>\n\n<div id=\"acf-block-6a019df5cb376\" class=\"block wrapped-content\">\n    <div class=\"wrapper\">\n        <div class=\"inner-wrapper\">\n                \n<div id=\"acf-block-6a019df5cb4b4\" class=\"block-wysiwyg\">\n            \n\n<h4 style=\"color: #41b6e6\">Motor disturbances<\/h4>\n\n<ul class=\"no-left\">\n<li>41% report motor difficulty as the first symptom<sup><sup>5<\/sup><\/sup><\/li>\n<\/ul>\n<h5><strong>Note: Unlike other NCLs, visual impairment isn&#8217;t typically present until later stages of the disease, well into the neurodegenerative decline of CLN2 disease.<sup>3<\/sup><\/strong><\/h5>\n\n    <\/div>\n        <\/div>\n    <\/div>\n<\/div>\n\n<div id=\"acf-block-6a019df5cb4f2\" class=\"block wrapped-content\">\n    <div class=\"wrapper\">\n        <div class=\"inner-wrapper\">\n                \n<figure id=\"acf-block-6a019df5cb530\">\n    <div class=\"image image-align-left\">\n                    <img decoding=\"async\" class=\"\" src=\"https:\/\/hcp.biomarin.com\/en-us\/cln2\/wp-content\/uploads\/sites\/3\/2026\/05\/hr-1900x2.png\" alt=\"\" \/>            <\/div>\n    <\/figure>\n        <\/div>\n    <\/div>\n<\/div>\n\n<div id=\"acf-block-6a019df5cb376\" class=\"block wrapped-content block-tight-bottom\">\n    <div class=\"wrapper\">\n        <div class=\"inner-wrapper\">\n                \n<div id=\"acf-block-6a019df5cb4b4\" class=\"block-wysiwyg\">\n            \n\n<h2 style=\"font-weight: bold\">Electrophysiological and radiological findings may provide early signals of CLN2 disease<\/h2>\n\n\n    <\/div>\n        <\/div>\n    <\/div>\n<\/div>\n\n<div id=\"acf-block-6a01c0140ef82\" class=\"block boxed-content boxed-content-no-bg\">\n\t<div class=\"wrapper\">\n\t\t<div class=\"inner-wrapper\">\n\t\t\t<div class=\"box\">\n\t\t\t\t\t\t\t\t\n<div id=\"acf-block-6a01c0140f27f\" class=\"image-text-block bottom-border\">\n            <div class=\"image-block small\">\n            <figure>\n                <div class=\"image image-rounded\">\n                    <img decoding=\"async\" class=\"\" src=\"https:\/\/hcp.biomarin.com\/en-us\/cln2\/wp-content\/uploads\/sites\/3\/2026\/05\/Electrophysiological.png?v=0.4\" alt=\"\" \/>                <\/div>\n            <\/figure>\n        <\/div>\n        <div class=\"content-block\">\n                    <h3>Electroencephalogram (EEG) with low-frequency (1-2 Hz) intermittent photic stimulation (IPS) elicits a distinguishing photoparoxysmal response (PPR) in the majority of children with CLN2 disease<sup>7<\/sup>\n<\/h3>\n                            <p>According to a study of children with CLN2 disease, PPR was<sup>7<\/sup>:<\/p>\n<ul class=\"no-left\">\n<li>Seen in 60% of children<\/li>\n<li>Identified on the initial EEG in 78% of cases<\/li>\n<li>Detected in time-locked fashion in 63% of cases<\/li>\n<\/ul>\n                    <\/div>\n<\/div>\n\n<div id=\"acf-block-6a01c0140f332\" class=\"image-text-block block-tight-bottom\">\n            <div class=\"image-block small\">\n            <figure>\n                <div class=\"image image-rounded\">\n                    <img decoding=\"async\" class=\"\" src=\"https:\/\/hcp.biomarin.com\/en-us\/cln2\/wp-content\/uploads\/sites\/3\/2026\/05\/atrophy.png?v=0.4\" alt=\"\" \/>                <\/div>\n            <\/figure>\n        <\/div>\n        <div class=\"content-block\">\n                    <h3>Early in the disease, a brain MRI may appear normal or show subtle abnormalities<sup>3,8<\/sup>\n<\/h3>\n                            <p>Abnormalities include:<\/p>\n<p><img decoding=\"async\" src=\"https:\/\/hcp.biomarin.com\/en-us\/cln2\/wp-content\/uploads\/sites\/3\/2026\/09\/Abnormalities.jpg?v=0.4\" \/><\/p>\n<p class=\"footnoteFont\">Photos courtesy of Ludovico D\u2019Incerti, MD.<\/p>\n<p>Later in the disease, cerebral atrophy becomes evident at the cerebellum.<\/p>\n                    <\/div>\n<\/div>\n\t\t\t<\/div>\n\t\t<\/div>\n\t<\/div>\n<\/div>\n\n<div id=\"acf-block-6a019df5cb376\" class=\"block wrapped-content\">\n    <div class=\"wrapper\">\n        <div class=\"inner-wrapper\">\n                \n<div id=\"acf-block-6a019df5cb4b4\" class=\"block-wysiwyg\">\n            <p><strong>Not all children with CLN2 disease will exhibit these findings. A definitive diagnosis should be confirmed through laboratory testing.<\/strong><\/p>\n    <\/div>\n        <\/div>\n    <\/div>\n<\/div>\n\n<div id=\"acf-block-6a019df5cb4f2\" class=\"block wrapped-content\">\n    <div class=\"wrapper\">\n        <div class=\"inner-wrapper\">\n                \n<figure id=\"acf-block-6a019df5cb530\">\n    <div class=\"image image-align-left\">\n                    <img decoding=\"async\" class=\"\" src=\"https:\/\/hcp.biomarin.com\/en-us\/cln2\/wp-content\/uploads\/sites\/3\/2026\/05\/hr-1900x2.png\" alt=\"\" \/>            <\/div>\n    <\/figure>\n        <\/div>\n    <\/div>\n<\/div>\n\n<div id=\"acf-block-6a01c0140f407\" class=\"block boxed-content boxed-content-no-bg\">\n\t<div class=\"wrapper\">\n\t\t<div class=\"inner-wrapper\">\n\t\t\t<div class=\"box\">\n\t\t\t\t\t\t\t\t\n<div id=\"acf-block-6a01c0140f47a\" class=\"image-text-block\">\n            <div class=\"image-block small\">\n            <figure>\n                <div class=\"image image-rounded\">\n                    <img decoding=\"async\" class=\"\" src=\"https:\/\/hcp.biomarin.com\/en-us\/cln2\/wp-content\/uploads\/sites\/3\/2026\/05\/behind-seizure-logo.png?v=0.4\" alt=\"\" \/>                <\/div>\n            <\/figure>\n        <\/div>\n        <div class=\"content-block\">\n                            \n\n<p>BioMarin has partnered with Invitae\/Lacorp to bring you the Behind the Seizure<sup>\u00ae<\/sup> program\u2014a no-cost epilepsy gene panel testing program to help health care providers diagnose CLN2 disease earlier.<\/p>\n\n\n<p>In as little as 2 weeks, an epilepsy gene panel test can bring you and your eligible patients closer to identifying if there is a genetic cause <em>behind the seizure.<\/em><\/p>\n<p><strong>Visit <a href=\"https:\/\/www.invitae.com\/sponsored-testing\/behind-the-seizure\" target=\"_blank\" rel=\"noopener\">Behind the Seizure<\/a> to learn more and to order a test.<\/strong><\/p>\n                    <\/div>\n<\/div>\n\t\t\t<\/div>\n\t\t<\/div>\n\t<\/div>\n<\/div>\n\n<div id=\"acf-block-6a019df5cb4f2\" class=\"block wrapped-content\">\n    <div class=\"wrapper\">\n        <div class=\"inner-wrapper\">\n                \n<figure id=\"acf-block-6a019df5cb530\">\n    <div class=\"image image-align-left\">\n                    <img decoding=\"async\" class=\"\" src=\"https:\/\/hcp.biomarin.com\/en-us\/cln2\/wp-content\/uploads\/sites\/3\/2026\/05\/hr-1900x2.png\" alt=\"\" \/>            <\/div>\n    <\/figure>\n        <\/div>\n    <\/div>\n<\/div>\n\n<div id=\"acf-block-6a01c0140f7ff\" class=\"block references\">\n    <div class=\"wrapper\">\n\t\t<div class=\"inner-wrapper\">\n\t\t    \t\t\t    <h4>References:\n<\/h4>\n\t\t\t\t\t\t                <ol>\n                                                                                                                        <li><span>Schulz A, Kohlsch\u00fctter A, Mink J, Simonati A, Williams R. NCL diseases \u2013 clinical perspectives. <em>Biochimica et Biophysica Acta.<\/em> 2013;1832:1801\u20131806.\n<\/span><\/li>\n                                                                                                                                                <li><span>Schulz A, Cohen-Pfeffer JL, Crystal R, et al. Neuronal ceroid lipofuscinosis-2 (CLN2) disorder, a type of Batten disease caused by TPP1 enzyme deficiency: current knowledge of the natural history from international experts. Poster session presented at: The Society for the Study of Inborn Errors of Metabolism (SSIEM) Annual Symposium; September 2015; Lyon, France.\n<\/span><\/li>\n                                                                                                                                                <li><span>Chang M, Cooper JD, Davidson BL, et al. CLN2. In: Mole S, Williams R, and Goebel H, eds. <em>The neuronal ceroid lipofuscinoses (Batten Disease).<\/em> 2nd ed. Oxford, United Kingdom: Oxford University Press; 2011:80-109.\n<\/span><\/li>\n                                                                                                                                                <li><span>P\u00e9rez-Poyato MS, Marfa MP, Abizanda IF, et al. Late infantile neuronal ceroid lipofuscinosis: mutations in the CLN2 gene and clinical course in Spanish patients. <em>J Child Neurol.<\/em> 2013;28:470-478.\n<\/span><\/li>\n                                                                                                                                                <li><span>Nickel M, Simonati A, Jacoby D, et al. Disease characteristics and progression in patients with late-infantile neuronal ceroid lipofuscinosis type 2 (CLN2) disease: an observational cohort study. <em>Lancet Child Adolesc Health.<\/em> 2018 Aug;2(8):582-590. doi: 10.1016\/S2352-4642(18)30179-2.\n<\/span><\/li>\n                                                                                                                                                <li><span>\u00c5ndell E, Tomson T, Carlsson S, et al. The incidence of unprovoked seizures and occurrence of neurodevelopmental comordities in children at the time of their first epileptic seizure and during the subsequent six months. <em>Epilepsy Res.<\/em> 2015;113:140-150.\n<\/span><\/li>\n                                                                                                                                                <li><span>Albert DV, Yin H, De Los Reyes EC, Vidaurre J. Unique Characteristics of the photoparoxysmal response in patients with neuronal ceroid lipofuscinosis type 2: can EEG be a biomarker? <em>J Child Neurol.<\/em> 2016;31:1475-1482.\n<\/span><\/li>\n                                                                                                                                                <li><span>Mole SE, Williams RE, and Goebel HH. Correlations between genotype, ultrastructural morphology and clinical phenotype in the neuronal ceroid lipofuscinoses. <em>Neurogenetics.<\/em> 2005;6:107-126.\n<\/span><\/li>\n                                                            <\/ol>\n\t\t\t\t\t<\/div>\n\t<\/div>\n<\/div>","protected":false},"excerpt":{"rendered":"","protected":false},"author":2,"featured_media":0,"parent":26,"menu_order":0,"comment_status":"closed","ping_status":"closed","template":"","meta":{"_acf_changed":false,"inline_featured_image":false,"footnotes":""},"class_list":["post-34","page","type-page","status-publish","hentry"],"acf":[],"yoast_head":"<!-- This site is optimized with the Yoast SEO plugin v28.2 - https:\/\/yoast.com\/product\/yoast-seo-wordpress\/ -->\n<title>CLN2 Connection | Recognize the early signs | HCP BioMarin<\/title>\n<meta name=\"description\" content=\"Learn to recognise the early signs of CLN2 disease, including seizures and language delay, to help support earlier diagnosis and genetic testing.\" \/>\n<meta name=\"robots\" content=\"index, follow, max-snippet:-1, max-image-preview:large, max-video-preview:-1\" \/>\n<link rel=\"canonical\" href=\"https:\/\/hcp.biomarin.com\/en-us\/cln2\/identification-diagnosis\/recognise-the-early-signs\/\" \/>\n<meta property=\"og:locale\" content=\"en_US\" \/>\n<meta property=\"og:type\" content=\"article\" \/>\n<meta property=\"og:title\" content=\"CLN2 Connection | Recognize the early signs | HCP BioMarin\" \/>\n<meta property=\"og:description\" content=\"Learn to recognise the early signs of CLN2 disease, including seizures and language delay, to help support earlier diagnosis and genetic testing.\" \/>\n<meta property=\"og:url\" content=\"https:\/\/hcp.biomarin.com\/en-us\/cln2\/identification-diagnosis\/recognise-the-early-signs\/\" \/>\n<meta property=\"og:site_name\" content=\"BMRN CLN2 DSE HCP EN-US\" \/>\n<meta property=\"article:modified_time\" content=\"2026-09-15T13:54:13+00:00\" \/>\n<meta name=\"twitter:card\" content=\"summary_large_image\" \/>\n<script type=\"application\/ld+json\" class=\"yoast-schema-graph\">{\"@context\":\"https:\\\/\\\/schema.org\",\"@graph\":[{\"@type\":\"WebPage\",\"@id\":\"https:\\\/\\\/hcp.biomarin.com\\\/en-us\\\/cln2\\\/identification-diagnosis\\\/recognise-the-early-signs\\\/\",\"url\":\"https:\\\/\\\/hcp.biomarin.com\\\/en-us\\\/cln2\\\/identification-diagnosis\\\/recognise-the-early-signs\\\/\",\"name\":\"CLN2 Connection | Recognize the early signs | HCP BioMarin\",\"isPartOf\":{\"@id\":\"https:\\\/\\\/hcp.biomarin.com\\\/en-us\\\/cln2\\\/#website\"},\"datePublished\":\"2026-05-07T10:44:30+00:00\",\"dateModified\":\"2026-09-15T13:54:13+00:00\",\"description\":\"Learn to recognise the early signs of CLN2 disease, including seizures and language delay, to help support earlier diagnosis and genetic testing.\",\"breadcrumb\":{\"@id\":\"https:\\\/\\\/hcp.biomarin.com\\\/en-us\\\/cln2\\\/identification-diagnosis\\\/recognise-the-early-signs\\\/#breadcrumb\"},\"inLanguage\":\"en-US\",\"potentialAction\":[{\"@type\":\"ReadAction\",\"target\":[\"https:\\\/\\\/hcp.biomarin.com\\\/en-us\\\/cln2\\\/identification-diagnosis\\\/recognise-the-early-signs\\\/\"]}]},{\"@type\":\"BreadcrumbList\",\"@id\":\"https:\\\/\\\/hcp.biomarin.com\\\/en-us\\\/cln2\\\/identification-diagnosis\\\/recognise-the-early-signs\\\/#breadcrumb\",\"itemListElement\":[{\"@type\":\"ListItem\",\"position\":1,\"name\":\"Home\",\"item\":\"https:\\\/\\\/hcp.biomarin.com\\\/en-us\\\/cln2\\\/\"},{\"@type\":\"ListItem\",\"position\":2,\"name\":\"Identification &amp; 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