{"id":85422,"date":"2024-11-14T14:23:39","date_gmt":"2024-11-14T05:23:39","guid":{"rendered":"https:\/\/www.hiro-clinic.or.jp\/nipt\/8p23-1-deletion-syndrome\/"},"modified":"2025-08-22T17:26:37","modified_gmt":"2025-08-22T08:26:37","slug":"8p23-1-deletion-syndrome","status":"publish","type":"post","link":"https:\/\/www.hiro-clinic.or.jp\/nipt\/8p23-1-deletion-syndrome\/?lang=en","title":{"rendered":"8p23.1 Deletion Syndrome"},"content":{"rendered":"\n<div style=\"border:solid #ffe6e6 0.8rem;background-color: #fff9f9;padding:3% 5%;margin:1rem 0 3rem;\"><h2 style=\"margin-top:1rem;\">\u3053\u306e\u8a18\u4e8b\u306e\u307e\u3068\u3081<\/h2><p>\u672c\u8a18\u4e8b\u3067\u306f\u30018p23.1\u9818\u57df\u306b\u95a2\u9023\u3059\u308b\u7a00\u5c11\u75be\u60a3\u3067\u3042\u308b\u5bb6\u65cf\u6027\u82e5\u5e74\u7cd6\u5c3f\u75c5\uff08MODY\uff09\u3001\u5148\u5929\u6027\u6a2a\u9694\u819c\u30d8\u30eb\u30cb\u30a2\uff08CDH\uff09\u3001\u30b9\u30af\u30a2\u30ec\u30f3\u5408\u6210\u9175\u7d20\u6b20\u640d\u75c7\uff08SQSD\uff09\u306b\u3064\u3044\u3066\u89e3\u8aac\u3057\u307e\u3059\u3002\u3053\u308c\u3089\u306e\u75be\u60a3\u306b\u95a2\u4e0e\u3059\u308b\u907a\u4f1d\u5b50BLK\u3001GATA4\u3001FDFT1\u306e\u5f79\u5272\u3084\u75c7\u72b6\u3001\u8a3a\u65ad\u6cd5\u3001\u7ba1\u7406\u306e\u91cd\u8981\u6027\u3092\u308f\u304b\u308a\u3084\u3059\u304f\u8aac\u660e\u3057\u307e\u3059\u3002<\/p><\/div>\n\n\n\n<div id=\"ez-toc-container\" class=\"ez-toc-v2_0_84 counter-hierarchy ez-toc-counter ez-toc-grey ez-toc-container-direction\">\n<div class=\"ez-toc-title-container\">\n<p class=\"ez-toc-title\" style=\"cursor:inherit\">\u76ee\u6b21<\/p>\n<span class=\"ez-toc-title-toggle\"><a href=\"#\" class=\"ez-toc-pull-right ez-toc-btn ez-toc-btn-xs ez-toc-btn-default ez-toc-toggle\" aria-label=\"Toggle Table of Content\"><span class=\"ez-toc-js-icon-con\"><span class=\"\"><span class=\"eztoc-hide\" style=\"display:none;\">Toggle<\/span><span class=\"ez-toc-icon-toggle-span\"><svg style=\"fill: #999;color:#999\" xmlns=\"http:\/\/www.w3.org\/2000\/svg\" class=\"list-377408\" width=\"20px\" height=\"20px\" viewBox=\"0 0 24 24\" fill=\"none\"><path d=\"M6 6H4v2h2V6zm14 0H8v2h12V6zM4 11h2v2H4v-2zm16 0H8v2h12v-2zM4 16h2v2H4v-2zm16 0H8v2h12v-2z\" fill=\"currentColor\"><\/path><\/svg><svg style=\"fill: #999;color:#999\" class=\"arrow-unsorted-368013\" xmlns=\"http:\/\/www.w3.org\/2000\/svg\" width=\"10px\" height=\"10px\" viewBox=\"0 0 24 24\" version=\"1.2\" baseProfile=\"tiny\"><path d=\"M18.2 9.3l-6.2-6.3-6.2 6.3c-.2.2-.3.4-.3.7s.1.5.3.7c.2.2.4.3.7.3h11c.3 0 .5-.1.7-.3.2-.2.3-.5.3-.7s-.1-.5-.3-.7zM5.8 14.7l6.2 6.3 6.2-6.3c.2-.2.3-.5.3-.7s-.1-.5-.3-.7c-.2-.2-.4-.3-.7-.3h-11c-.3 0-.5.1-.7.3-.2.2-.3.5-.3.7s.1.5.3.7z\"\/><\/svg><\/span><\/span><\/span><\/a><\/span><\/div>\n<nav><ul class='ez-toc-list ez-toc-list-level-1 ' ><li class='ez-toc-page-1 ez-toc-heading-level-2'><a class=\"ez-toc-link ez-toc-heading-1\" href=\"https:\/\/www.hiro-clinic.or.jp\/nipt\/8p23-1-deletion-syndrome\/?lang=en\/#Genes_and_Their_Associated_Disorders\" >Genes and Their Associated Disorders<\/a><\/li><li class='ez-toc-page-1 ez-toc-heading-level-2'><a class=\"ez-toc-link ez-toc-heading-2\" href=\"https:\/\/www.hiro-clinic.or.jp\/nipt\/8p23-1-deletion-syndrome\/?lang=en\/#1_BLK_Maturity-Onset_Diabetes_of_the_Young_MODY\" >[1. BLK] Maturity-Onset Diabetes of the Young (MODY)<\/a><\/li><li class='ez-toc-page-1 ez-toc-heading-level-2'><a class=\"ez-toc-link ez-toc-heading-3\" href=\"https:\/\/www.hiro-clinic.or.jp\/nipt\/8p23-1-deletion-syndrome\/?lang=en\/#2_GATA4_Congenital_Diaphragmatic_Hernia_CDH\" >[2. GATA4] Congenital Diaphragmatic Hernia (CDH)<\/a><\/li><li class='ez-toc-page-1 ez-toc-heading-level-2'><a class=\"ez-toc-link ez-toc-heading-4\" href=\"https:\/\/www.hiro-clinic.or.jp\/nipt\/8p23-1-deletion-syndrome\/?lang=en\/#3_FDFT1_Squalene_Synthase_Deficiency_SQSD\" >[3. FDFT1] Squalene Synthase Deficiency (SQSD)<\/a><\/li><li class='ez-toc-page-1 ez-toc-heading-level-2'><a class=\"ez-toc-link ez-toc-heading-5\" href=\"https:\/\/www.hiro-clinic.or.jp\/nipt\/8p23-1-deletion-syndrome\/?lang=en\/#References\" >References:<\/a><\/li><\/ul><\/nav><\/div>\n<h2 class=\"wp-block-heading\"><span class=\"ez-toc-section\" id=\"Genes_and_Their_Associated_Disorders\"><\/span>Genes and Their Associated Disorders<span class=\"ez-toc-section-end\"><\/span><\/h2>\n\n\n<div class=\"wp-block-image\">\n<figure class=\"aligncenter size-large\"><img decoding=\"async\" width=\"1024\" height=\"20\" src=\"\/nipt\/wp-content\/uploads\/2024\/11\/1a10af4ded232ea8e2cfb45ed01991bf-1024x20.png\" alt=\"8p23.1\u3000\" class=\"wp-image-90706\"\/><\/figure><\/div>\n\n\n<figure class=\"wp-block-table\"><table class=\"has-fixed-layout\"><thead><tr><th>S\/N<\/th><th>Gene<\/th><th>Associated Disorder (Japanese)<\/th><th>Associated Disorder (English)<\/th><\/tr><\/thead><tbody><tr><td>1<\/td><td><strong>BLK<\/strong><\/td><td>\u5bb6\u65cf\u6027\u82e5\u5e74\u7cd6\u5c3f\u75c5<\/td><td>Maturity-Onset Diabetes of the Young (MODY)<\/td><\/tr><tr><td>2<\/td><td><strong>GATA4<\/strong><\/td><td>\u5148\u5929\u6027\u6a2a\u9694\u819c\u30d8\u30eb\u30cb\u30a2<\/td><td>Congenital Diaphragmatic Hernia (CDH)<\/td><\/tr><tr><td>3<\/td><td><strong>FDFT1<\/strong><\/td><td>\u30b9\u30af\u30a2\u30ec\u30f3\u5408\u6210\u9175\u7d20\u6b20\u640d\u75c7<\/td><td>Squalene Synthase Deficiency (SQSD)<\/td><\/tr><\/tbody><\/table><\/figure>\n\n\n\n<div style=\"height:16px\" aria-hidden=\"true\" class=\"wp-block-spacer\"><\/div>\n\n\n<div class=\"wp-block-image\">\n<figure class=\"aligncenter size-full\"><img decoding=\"async\" width=\"937\" height=\"500\" src=\"\/nipt\/wp-content\/uploads\/2024\/11\/chromo8-MeGeQbFLKdNAAAFRJQAAADdS.png\" alt=\"chromo8 \" class=\"wp-image-90710\"\/><\/figure><\/div>\n\n\n<div style=\"height:16px\" aria-hidden=\"true\" class=\"wp-block-spacer\"><\/div>\n\n\n\n<h2 class=\"wp-block-heading\"><span class=\"ez-toc-section\" id=\"1_BLK_Maturity-Onset_Diabetes_of_the_Young_MODY\"><\/span>[1. BLK] Maturity-Onset Diabetes of the Young (MODY)<span class=\"ez-toc-section-end\"><\/span><\/h2>\n\n\n<div class=\"wp-block-image\">\n<figure class=\"aligncenter size-large\"><img decoding=\"async\" width=\"1024\" height=\"20\" src=\"\/nipt\/wp-content\/uploads\/2024\/11\/1a10af4ded232ea8e2cfb45ed01991bf-1024x20.png\" alt=\"8p23.1\u3000\" class=\"wp-image-90706\"\/><\/figure><\/div>\n\n<div class=\"wp-block-image\">\n<figure class=\"aligncenter size-large\"><img decoding=\"async\" width=\"1024\" height=\"20\" src=\"\/nipt\/wp-content\/uploads\/2024\/11\/BLK-hgtIdeo_genome_25b92_deb420-1024x20.png\" alt=\"BLK \" class=\"wp-image-90717\"\/><\/figure><\/div>\n\n\n<div style=\"height:16px\" aria-hidden=\"true\" class=\"wp-block-spacer\"><\/div>\n\n\n\n<p><strong>MODY<\/strong> is a group of <strong>non-autoimmune, genetically-driven diabetes disorders<\/strong> that typically manifest during adolescence or early adulthood. The <strong>BLK gene<\/strong>, located in the <strong>8p23.1 region<\/strong>, is associated with <strong>MODY11<\/strong>, an extremely rare subtype accounting for <strong>less than 1% of all MODY cases<\/strong>. The primary pathophysiology of this form is <strong>impaired insulin secretion<\/strong>.<\/p>\n\n\n\n<p>MODY usually presents <strong>before age 35<\/strong> and is distinct from <strong>type 1<\/strong> and <strong>type 2 diabetes<\/strong>. In type 1 diabetes, islet autoantibodies are present, whereas in MODY they are absent. Endogenous insulin secretion often continues beyond the initial &#8220;honeymoon period,&#8221; and patients may achieve glycemic control with <strong>low-dose insulin therapy (&lt;0.5 U\/kg\/day)<\/strong>. Additionally, diabetic ketoacidosis rarely develops during periods of insulin interruption.<\/p>\n\n\n\n<div style=\"height:16px\" aria-hidden=\"true\" class=\"wp-block-spacer\"><\/div>\n\n\n<div class=\"wp-block-image\">\n<figure class=\"aligncenter size-full\"><img decoding=\"async\" width=\"640\" height=\"430\" src=\"\/nipt\/wp-content\/uploads\/2024\/11\/24326790_s.jpg\" alt=\"\u671d\u306e\u8840\u7cd6\u5024\" class=\"wp-image-90722\"\/><\/figure><\/div>\n\n\n<div style=\"height:16px\" aria-hidden=\"true\" class=\"wp-block-spacer\"><\/div>\n\n\n\n<p>Distinguishing MODY from type 2 diabetes involves recognizing <strong>the absence of obesity or acanthosis nigricans<\/strong> and <strong>normal triglyceride and elevated HDL cholesterol levels<\/strong>. Patients often show <strong>persistent fasting hyperglycemia<\/strong> with <strong>limited responsiveness to pharmacological treatments<\/strong> but may demonstrate <strong>heightened sensitivity to sulfonylureas<\/strong>.<\/p>\n\n\n\n<p>A <strong>molecular genetic test<\/strong> is typically performed when MODY is suspected based on <strong>family history<\/strong> and <strong>clinical features<\/strong>, such as early-onset diabetes (before 35) or a dominant inheritance pattern. MODY is transmitted in an <strong>autosomal dominant manner<\/strong>, and its familial presentation differs from type 1 and type 2 diabetes.<\/p>\n\n\n\n<div style=\"height:16px\" aria-hidden=\"true\" class=\"wp-block-spacer\"><\/div>\n\n\n<div class=\"wp-block-image\">\n<figure class=\"aligncenter size-full\"><img decoding=\"async\" width=\"640\" height=\"360\" src=\"\/nipt\/wp-content\/uploads\/2024\/11\/24906322_s.jpg\" alt=\"\u7cd6\u8cea\u5236\u9650\" class=\"wp-image-90725\"\/><\/figure><\/div>\n\n\n<div style=\"height:16px\" aria-hidden=\"true\" class=\"wp-block-spacer\"><\/div>\n\n\n\n<p>To date, <strong>at least 14 causative genes<\/strong> for MODY have been identified, with <strong>GCK (MODY2)<\/strong> and <strong>HNF1A (MODY3)<\/strong> mutations being the most common, together representing <strong>30\u201360% of cases<\/strong>. <strong>BLK-related MODY11<\/strong> remains very rare, sometimes presenting with clinical obesity. Accurate diagnosis of MODY requires a <strong>multifactorial approach<\/strong> that integrates family history, phenotype, and laboratory findings.<\/p>\n\n\n\n<p>Identifying the genetic cause of MODY not only optimizes <strong>individualized treatment<\/strong> but also supports <strong>genetic counseling<\/strong> and <strong>risk monitoring<\/strong> for family members. In the case of <strong>BLK-related MODY11<\/strong>, thorough clinical evaluation, a <strong>three-generation pedigree<\/strong>, physical examinations, and <strong>molecular testing<\/strong> are crucial for confirmation. Understanding the genetic background of this disorder is critical for <strong>tailoring treatment and improving patient outcomes<\/strong>.<\/p>\n\n\n\n<div style=\"height:15px\" aria-hidden=\"true\" class=\"wp-block-spacer\"><\/div>\n\n\n\n    <a href=\"\/nipt\/8q12-microduplication-syndrome\/\" class=\"blog-card\">\n      <div class=\"blog-card-content\">\n          <div class=\"blog-card-title\">8q12\u5fae\u5c0f\u91cd\u8907\u75c7\u5019\u7fa4 <\/div>\n          <div class=\"blog-card-excerpt\">8q12\u5fae\u5c0f\u91cd\u8907\u75c7\u5019\u7fa4\u306e\u539f\u56e0\u3001\u4e3b\u306a\u75c7\u72b6\u3001\u6cbb\u7642\u6cd5\u3001\u4e88\u5f8c\u3001\u305d\u3057\u3066\u5bb6\u65cf\u304c\u5229\u7528\u3067\u304d\u308b\u652f\u63f4\u65b9\u6cd5\u306b\u3064\u3044\u3066\u89e3\u8aac\u3057\u307e\u3059\u3002\u9069\u5207\u306a\u7642\u80b2\u3068\u533b\u7642\u7ba1\u7406\u3067\u751f\u6d3b\u306e\u8cea\u3092\u5411\u4e0a...<\/div>\n      <\/div>\n    <\/a>\n\n\n\n\n\n\n<div style=\"height:16px\" aria-hidden=\"true\" class=\"wp-block-spacer\"><\/div>\n\n\n\n<h2 class=\"wp-block-heading\"><span class=\"ez-toc-section\" id=\"2_GATA4_Congenital_Diaphragmatic_Hernia_CDH\"><\/span>[2. GATA4] Congenital Diaphragmatic Hernia (CDH)<span class=\"ez-toc-section-end\"><\/span><\/h2>\n\n\n<div class=\"wp-block-image\">\n<figure class=\"aligncenter size-large\"><img decoding=\"async\" width=\"1024\" height=\"20\" src=\"\/nipt\/wp-content\/uploads\/2024\/11\/1a10af4ded232ea8e2cfb45ed01991bf-1024x20.png\" alt=\"8p23.1\u3000\" class=\"wp-image-90706\"\/><\/figure><\/div>\n\n<div class=\"wp-block-image\">\n<figure class=\"aligncenter size-large\"><img decoding=\"async\" width=\"1024\" height=\"20\" src=\"\/nipt\/wp-content\/uploads\/2024\/11\/0202096c5934a6454cf1663b439832f4-1024x20.png\" alt=\"GATA4\u3000\" class=\"wp-image-90728\"\/><\/figure><\/div>\n\n\n<div style=\"height:16px\" aria-hidden=\"true\" class=\"wp-block-spacer\"><\/div>\n\n\n\n<p><strong>Congenital Diaphragmatic Hernia (CDH)<\/strong> may occur <strong>in isolation<\/strong> or <strong>in combination with other congenital anomalies<\/strong>. Multiple factors contribute to its development, including <strong>chromosomal abnormalities<\/strong> and <strong>copy number variations (CNVs)<\/strong>. Among single-gene mutations, <strong>GATA4<\/strong>, located in the <strong>8p23.1 region<\/strong>, has been increasingly implicated in CDH pathogenesis.<\/p>\n\n\n\n<p>CDH typically presents at birth with <strong>severe respiratory distress<\/strong>, caused by abdominal organs herniating into the thoracic cavity, thereby <strong>hindering lung development<\/strong>. Severity varies; some patients experience only mild respiratory or gastrointestinal symptoms beyond the neonatal period, while others are asymptomatic and diagnosed incidentally via imaging.<\/p>\n\n\n\n<div style=\"height:16px\" aria-hidden=\"true\" class=\"wp-block-spacer\"><\/div>\n\n\n<div class=\"wp-block-image\">\n<figure class=\"aligncenter size-full\"><img decoding=\"async\" width=\"640\" height=\"424\" src=\"\/nipt\/wp-content\/uploads\/2024\/11\/25350468_s.jpg\" alt=\"\u304f\u307e\u306e\u306c\u3044\u3050\u308b\u307f\" class=\"wp-image-88669\"\/><\/figure><\/div>\n\n\n<div style=\"height:16px\" aria-hidden=\"true\" class=\"wp-block-spacer\"><\/div>\n\n\n\n<p>The most common anatomical type is the <strong>posterolateral defect (Bochdalek hernia)<\/strong>, which accounts for <strong>80\u201390% of CDH cases<\/strong>. Of these, <strong>85% occur on the left side<\/strong>, <strong>10% on the right<\/strong>, and <strong>5% bilaterally<\/strong>. Less common types include <strong>Morgagni hernias<\/strong> and <strong>central defects<\/strong>.<\/p>\n\n\n\n<p><strong>GATA4<\/strong> encodes a <strong>zinc finger transcription factor<\/strong> critical for the development of the diaphragm and lungs. Mutations have been observed in both <strong>familial and sporadic cases<\/strong>, often with <strong>incomplete penetrance<\/strong>. For example, in one family, a <strong>c.754C&gt;T (p.R252W)<\/strong> mutation led to mild diaphragmatic defects detectable only by MRI in asymptomatic carriers. In sporadic cases, <strong>de novo variants<\/strong> such as <strong>c.848G&gt;A (p.R283H)<\/strong> have been reported.<\/p>\n\n\n\n<div style=\"height:16px\" aria-hidden=\"true\" class=\"wp-block-spacer\"><\/div>\n\n\n<div class=\"wp-block-image\">\n<figure class=\"aligncenter size-full\"><img decoding=\"async\" width=\"640\" height=\"480\" src=\"\/nipt\/wp-content\/uploads\/2024\/11\/31127225_s.jpg\" alt=\"\u5bdd\u3066\u3044\u308b\u5b50\u4f9b\" class=\"wp-image-88779\"\/><\/figure><\/div>\n\n\n<div style=\"height:16px\" aria-hidden=\"true\" class=\"wp-block-spacer\"><\/div>\n\n\n\n<p>Animal studies support these findings: inhibition of <strong>GATA4 expression<\/strong> leads to diaphragm and lung malformations. Conversely, <strong>retinoic acid treatments<\/strong> have been shown to upregulate <strong>GATA4 expression<\/strong>, mitigating some developmental defects. This underscores the <strong>connection between GATA4 and retinoic acid pathways<\/strong> in diaphragm formation.<\/p>\n\n\n\n<p>Advances in <strong>genetic testing<\/strong>, particularly <strong>whole-exome sequencing (WES)<\/strong>, have enhanced the detection of rare variants associated with CDH, aiding in <strong>diagnosis, prognosis, and personalized care<\/strong>.<\/p>\n\n\n\n<p>Treatment primarily involves <strong>surgical repair<\/strong>, supported by <strong>respiratory management<\/strong>, <strong>nutritional support<\/strong>, and long-term multidisciplinary follow-up to address complications such as <strong>developmental delays<\/strong>, <strong>hearing loss<\/strong>, and <strong>thoracic deformities<\/strong>.<\/p>\n\n\n\n<p>Understanding <strong>GATA4&#8217;s role<\/strong> provides crucial insights into CDH pathophysiology and opens avenues for <strong>future therapeutic approaches<\/strong>.<\/p>\n\n\n\n<div style=\"height:15px\" aria-hidden=\"true\" class=\"wp-block-spacer\"><\/div>\n\n\n\n    <a href=\"\/nipt\/nablus-mask-like-facial-syndrome-overview\/\" class=\"blog-card\">\n      <div class=\"blog-card-content\">\n          <div class=\"blog-card-title\">\u30ca\u30d6\u30eb\u30b9\u4eee\u9762\u69d8\u9854\u75c7\u5019\u7fa4\uff08NMLFS; Nablus mask-like facial syndrome\uff09 <\/div>\n          <div class=\"blog-card-excerpt\">\u30ca\u30d6\u30eb\u30b9\u4eee\u9762\u69d8\u9854\u75c7\u5019\u7fa4\u306f\u3001\u9854\u8c8c\u7570\u5e38\u3084\u767a\u9054\u9045\u6ede\u3092\u4f34\u3046\u975e\u5e38\u306b\u7a00\u306a\u907a\u4f1d\u6027\u75be\u60a3\u3067\u3059\u3002\u6700\u65b0\u306e\u75c7\u4f8b\u30fb\u8a3a\u65ad\u65b9\u6cd5\u30fb\u30b1\u30a2\u4f53\u5236\u3092\u308f\u304b\u308a\u3084\u3059\u304f\u7d39\u4ecb\u3057\u307e\u3059\u3002\uff5c\u30d2\u30ed\u30af...<\/div>\n      <\/div>\n    <\/a>\n\n\n\n\n\n\n<p><\/p>\n\n\n\n<h2 class=\"wp-block-heading\"><span class=\"ez-toc-section\" id=\"3_FDFT1_Squalene_Synthase_Deficiency_SQSD\"><\/span>[3. FDFT1] Squalene Synthase Deficiency (SQSD)<span class=\"ez-toc-section-end\"><\/span><\/h2>\n\n\n<div class=\"wp-block-image\">\n<figure class=\"aligncenter size-large\"><img decoding=\"async\" width=\"1024\" height=\"20\" src=\"\/nipt\/wp-content\/uploads\/2024\/11\/1a10af4ded232ea8e2cfb45ed01991bf-1024x20.png\" alt=\"8p23.1\u3000\" class=\"wp-image-90706\"\/><\/figure><\/div>\n\n<div class=\"wp-block-image\">\n<figure class=\"aligncenter size-large\"><img decoding=\"async\" width=\"1024\" height=\"20\" src=\"\/nipt\/wp-content\/uploads\/2024\/11\/FDFT1-hgtIdeo_genome_7589e_def210-1024x20.png\" alt=\"FDFT1 \" class=\"wp-image-90732\"\/><\/figure><\/div>\n\n\n<div style=\"height:16px\" aria-hidden=\"true\" class=\"wp-block-spacer\"><\/div>\n\n\n\n<p><strong>Squalene Synthase Deficiency (SQSD)<\/strong> is a <strong>rare congenital metabolic disorder<\/strong> affecting <strong>cholesterol biosynthesis<\/strong>. It is caused by <strong>biallelic pathogenic variants<\/strong> in the <strong>FDFT1 gene<\/strong>, located in the <strong>8p23.1 region<\/strong>.<\/p>\n\n\n\n<p><strong>Squalene synthase (SS)<\/strong> catalyzes the conversion of <strong>two molecules of farnesyl diphosphate (FPP) into squalene<\/strong>, a key step in cholesterol biosynthesis. Enzyme dysfunction disrupts cholesterol production, leading to <strong>multisystemic clinical manifestations<\/strong>.<\/p>\n\n\n\n<div style=\"height:16px\" aria-hidden=\"true\" class=\"wp-block-spacer\"><\/div>\n\n\n<div class=\"wp-block-image\">\n<figure class=\"aligncenter size-full\"><img decoding=\"async\" width=\"640\" height=\"480\" src=\"\/nipt\/wp-content\/uploads\/2024\/11\/30231096_s.jpg\" alt=\"\u304b\u3042\u3089\u3052\u3000\u9ad8\u30b3\u30ec\u30b9\u30c6\u30ed\u30fc\u30eb\" class=\"wp-image-90754\"\/><\/figure><\/div>\n\n\n<div style=\"height:16px\" aria-hidden=\"true\" class=\"wp-block-spacer\"><\/div>\n\n\n\n<p>Clinical features of SQSD resemble those of <strong>Smith-Lemli-Opitz syndrome (SLOS)<\/strong> and include:<\/p>\n\n\n\n<ul class=\"wp-block-list\">\n<li><strong>Facial dysmorphisms<\/strong> (narrow forehead, flat nasal bridge, posteriorly rotated ears)<\/li>\n\n\n\n<li><strong>Neonatal seizures<\/strong><\/li>\n\n\n\n<li><strong>Brain malformations<\/strong> (e.g., cortical malformations)<\/li>\n\n\n\n<li><strong>Visual impairment<\/strong> (optic nerve hypoplasia, cortical blindness)<\/li>\n\n\n\n<li><strong>Severe developmental delay and intellectual disability<\/strong><\/li>\n\n\n\n<li><strong>Dry skin and photosensitivity<\/strong><\/li>\n\n\n\n<li><strong>Genital anomalies<\/strong> in males (cryptorchidism, hypospadias)<\/li>\n\n\n\n<li>Additional signs: low birth weight, neonatal jaundice, and hepatic dysfunction.<\/li>\n<\/ul>\n\n\n\n<div style=\"height:16px\" aria-hidden=\"true\" class=\"wp-block-spacer\"><\/div>\n\n\n<div class=\"wp-block-image\">\n<figure class=\"aligncenter size-full\"><img decoding=\"async\" width=\"640\" height=\"427\" src=\"\/nipt\/wp-content\/uploads\/2024\/11\/29671411_s.jpg\" alt=\"UV\" class=\"wp-image-90760\"\/><\/figure><\/div>\n\n\n<div style=\"height:16px\" aria-hidden=\"true\" class=\"wp-block-spacer\"><\/div>\n\n\n\n<p>Diagnosis can be made by <strong>urine metabolic profiling<\/strong>, which reveals characteristic metabolites such as <strong>branched-chain dicarboxylic acids<\/strong> and <strong>farnesol-derived glucuronide conjugates<\/strong>. Techniques like <strong>gas chromatography\u2013mass spectrometry (GC-MS)<\/strong> and <strong>nuclear magnetic resonance spectroscopy (NMRS)<\/strong> are used. Genetic confirmation is achieved via <strong>molecular analysis of FDFT1<\/strong>.<\/p>\n\n\n\n<p>Currently, there is <strong>no curative treatment<\/strong>. Management is <strong>symptomatic<\/strong>, including standard interventions for seizures, developmental delays, constipation, and spasticity. <a href=\"https:\/\/www.hiro-clinic.or.jp\/nipt\/early-nipt-august-only\/\">Early<\/a> vision therapy, nutritional support (including gastrostomy feeding if needed), and melatonin for sleep disturbances can be beneficial. Patients should <strong>avoid sunlight exposure<\/strong> to manage photosensitivity.<\/p>\n\n\n\n<p>SQSD follows an <strong>autosomal recessive inheritance pattern<\/strong>, with a <strong>25% recurrence risk<\/strong> for siblings and <strong>50% chance of being asymptomatic carriers<\/strong>. Carrier testing and prenatal diagnosis are available when the familial FDFT1 variant is known.<\/p>\n\n\n\n<p>Research has demonstrated that <strong>FDFT1 variants reduce enzyme activity<\/strong>, causing toxic accumulation of intermediates like farnesyl diphosphate, which triggers <strong>cell growth inhibition<\/strong> and <strong>apoptosis<\/strong>. These findings highlight the critical role of cholesterol in <strong>embryogenesis and organ development<\/strong>.<\/p>\n\n\n\n<p>Reported cases remain limited, predominantly within <strong>European families<\/strong>, but awareness and accurate diagnosis are improving. With appropriate medical care and family support, patients&#8217; <strong>quality of life<\/strong> can be meaningfully enhanced.<\/p>\n\n\n\n<div style=\"height:15px\" aria-hidden=\"true\" class=\"wp-block-spacer\"><\/div>\n\n\n\n\n\n\n<h2 class=\"wp-block-heading\"><span class=\"ez-toc-section\" id=\"References\"><\/span>References:<span class=\"ez-toc-section-end\"><\/span><\/h2>\n\n\n<div class=\"wp-block-image\">\n<figure class=\"aligncenter size-full\"><img decoding=\"async\" width=\"640\" height=\"427\" src=\"\/nipt\/wp-content\/uploads\/2024\/11\/24156031_s.jpg\" alt=\"\u5b50\u3069\u3082\u3092\u611b\u3055\u306a\u3044\u3068\" class=\"wp-image-87708\"\/><\/figure><\/div>\n\n\n<div style=\"height:15px\" aria-hidden=\"true\" class=\"wp-block-spacer\"><\/div>\n\n\n\n<ul class=\"wp-block-list\">\n<li><a href=\"https:\/\/doi.org\/10.1016\/j.ajhg.2018.05.004\">Coman, D., Vissers, L. E. L. M., Riley, L. G., Kwint, M. P., Hauck, R., Koster, J., Geuer, S., Hopkins, S., Hallinan, B., Sweetman, L., Engelke, U. F. H., Burrow, T. A., Cardinal, J., McGill, J., Inwood, A., Gurnsey, C., Waterham, H. R., Christodoulou, J., Wevers, R. A., &amp; Pitt, J. (2018). Squalene synthase deficiency: Clinical, biochemical, and molecular characterization of a defect in cholesterol biosynthesis. <em>The American Journal of Human Genetics<\/em>, <em>103<\/em>(1), 125\u2013130. https:\/\/doi.org\/10.1016\/j.ajhg.2018.05.004<\/a><\/li>\n\n\n\n<li><a href=\"https:\/\/www.ncbi.nlm.nih.gov\/books\/NBK553533\/\">Coman D, Vissers L, Waterham H, et al. Squalene Synthase Deficiency. 2020 Feb 6. In: Adam MP, Feldman J, Mirzaa GM, et al., editors. GeneReviews\u00ae [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2025. Available from: https:\/\/www.ncbi.nlm.nih.gov\/books\/NBK553533\/<\/a><\/li>\n\n\n\n<li><a href=\"https:\/\/doi.org\/10.1007\/s00439-012-1249-0\">Yu, L., Wynn, J., Cheung, Y. H., Shen, Y., Mychaliska, G. B., Crombleholme, T. M., Azarow, K. S., Lim, F. Y., Chung, D. H., Potoka, D., Warner, B. W., Bucher, B., Stolar, C., Aspelund, G., Arkovitz, M. S., &amp; Chung, W. K. (2013). Variants in GATA4 are a rare cause of familial and sporadic congenital diaphragmatic hernia. <em>Human genetics<\/em>, <em>132<\/em>(3), 285\u2013292. https:\/\/doi.org\/10.1007\/s00439-012-1249-0<\/a><\/li>\n\n\n\n<li><a href=\"https:\/\/www.ncbi.nlm.nih.gov\/books\/NBK1359\/\">Longoni M, Pober BR, High FA. Congenital Diaphragmatic Hernia Overview. 2006 Feb 1 [Updated 2020 Nov 5]. In: Adam MP, Feldman J, Mirzaa GM, et al., editors. GeneReviews\u00ae [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2025. Available from: https:\/\/www.ncbi.nlm.nih.gov\/books\/NBK1359\/<\/a><\/li>\n\n\n\n<li><a href=\"https:\/\/www.ncbi.nlm.nih.gov\/books\/NBK500456\/\">Naylor R, Knight Johnson A, del Gaudio D. Maturity-Onset Diabetes of the Young Overview. 2018 May 24. In: Adam MP, Feldman J, Mirzaa GM, et al., editors. GeneReviews\u00ae [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2025. Available from: https:\/\/www.ncbi.nlm.nih.gov\/books\/NBK500456\/<\/a><\/li>\n\n\n\n<li><a href=\"https:\/\/doi.org\/10.1093\/nar\/gkae974\">Perez, G., Barber, G. P., Benet-Pages, A., Casper, J., Clawson, H., Diekhans, M., Fischer, C., Gonzalez, J. N., Hinrichs, A. S., Lee, C. M., Nassar, L. R., Raney, B. J., Speir, M. L., van Baren, M. J., Vaske, C. J., Haussler, D., Kent, W. J., &amp; Haeussler, M. (2024). The UCSC Genome Browser database: 2025 update. Nucleic Acids Research, gkae974. https:\/\/doi.org\/10.1093\/nar\/gkae974<\/a><\/li>\n\n\n\n<li><a href=\"https:\/\/doi.org\/10.1093\/nar\/gkad1049\">Harrison, P. W., Amode, M. R., Austine-Orimoloye, O., Azov, A. G., Barba, M., Barnes, I., Becker, A., Bennett, R., Berry, A., Bhai, J., Bhurji, S. K., Boddu, S., Branco Lins, P. R., Brooks, L., Budhanuru Ramaraju, S., Campbell, L. I., Carbajo Martinez, M., Charkhchi, M., Chougule, K., \u2026 Yates, A. D. (2024). Ensembl 2024. Nucleic Acids Research, 52(D1), D891\u2013D899. https:\/\/doi.org\/10.1093\/nar\/gkad1049<\/a><\/li>\n<\/ul>\n\n\n\n<div style=\"height:16px\" aria-hidden=\"true\" class=\"wp-block-spacer\"><\/div>\n\n\n\n","protected":false},"excerpt":{"rendered":"\u3053\u306e\u8a18\u4e8b\u306e\u307e\u3068\u3081\u672c\u8a18\u4e8b\u3067\u306f\u30018p23.1&#8230;\n <a href=\"https:\/\/www.hiro-clinic.or.jp\/nipt\/8p23-1-deletion-syndrome\/?lang=en\">\u7d9a\u304d\u3092\u8aad\u3080<\/a>","protected":false},"author":101,"featured_media":89761,"comment_status":"closed","ping_status":"closed","sticky":false,"template":"","format":"standard","meta":{"_acf_changed":false,"footnotes":""},"categories":[97],"tags":[],"class_list":["post-85422","post","type-post","status-publish","format-standard","has-post-thumbnail","hentry","category-uncategorized"],"acf":[],"_links":{"self":[{"href":"https:\/\/www.hiro-clinic.or.jp\/nipt\/wp-json\/wp\/v2\/posts\/85422","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/www.hiro-clinic.or.jp\/nipt\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/www.hiro-clinic.or.jp\/nipt\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/www.hiro-clinic.or.jp\/nipt\/wp-json\/wp\/v2\/users\/101"}],"replies":[{"embeddable":true,"href":"https:\/\/www.hiro-clinic.or.jp\/nipt\/wp-json\/wp\/v2\/comments?post=85422"}],"version-history":[{"count":20,"href":"https:\/\/www.hiro-clinic.or.jp\/nipt\/wp-json\/wp\/v2\/posts\/85422\/revisions"}],"predecessor-version":[{"id":112092,"href":"https:\/\/www.hiro-clinic.or.jp\/nipt\/wp-json\/wp\/v2\/posts\/85422\/revisions\/112092"}],"wp:featuredmedia":[{"embeddable":true,"href":"https:\/\/www.hiro-clinic.or.jp\/nipt\/wp-json\/wp\/v2\/media\/89761"}],"wp:attachment":[{"href":"https:\/\/www.hiro-clinic.or.jp\/nipt\/wp-json\/wp\/v2\/media?parent=85422"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/www.hiro-clinic.or.jp\/nipt\/wp-json\/wp\/v2\/categories?post=85422"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/www.hiro-clinic.or.jp\/nipt\/wp-json\/wp\/v2\/tags?post=85422"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}