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<title>Smith-Lemli-Opitz Syndrome - StatPearls - NCBI Bookshelf</title>
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<meta name="robots" content="INDEX,FOLLOW,NOARCHIVE" /><meta name="citation_inbook_title" content="StatPearls [Internet]" /><meta name="citation_title" content="Smith-Lemli-Opitz Syndrome" /><meta name="citation_publisher" content="StatPearls Publishing" /><meta name="citation_date" content="2024/01/11" /><meta name="citation_author" content="Aneil S. Sanghera" /><meta name="citation_author" content="Marco Zeppieri" /><meta name="citation_pmid" content="38261705" /><meta name="citation_fulltext_html_url" content="https://www.ncbi.nlm.nih.gov/books/NBK599510/" /><link rel="schema.DC" href="http://purl.org/DC/elements/1.0/" /><meta name="DC.Title" content="Smith-Lemli-Opitz Syndrome" /><meta name="DC.Type" content="Text" /><meta name="DC.Publisher" content="StatPearls Publishing" /><meta name="DC.Contributor" content="Aneil S. Sanghera" /><meta name="DC.Contributor" content="Marco Zeppieri" /><meta name="DC.Date" content="2024/01/11" /><meta name="DC.Identifier" content="https://www.ncbi.nlm.nih.gov/books/NBK599510/" /><meta name="description" content="Smith-Lemli-Opitz syndrome (SLOS) is a rare inherited condition characterized by a defect in cholesterol synthesis, resulting in low plasma cholesterol levels and raised levels of precursor 7-dehydrocholesterol (7-DHC).[1] The clinical manifestations result from a deficiency in 7-dehydrocholesterol reductase (DHCR-7).[2] In 1964, Dr. Smith, Dr. Lemli, and Dr. Opitz first described the condition based on a case series of 3 male pediatric patients who all presented with common abnormal clinical signs.[3]" /><meta name="og:title" content="Smith-Lemli-Opitz Syndrome" /><meta name="og:type" content="book" /><meta name="og:description" content="Smith-Lemli-Opitz syndrome (SLOS) is a rare inherited condition characterized by a defect in cholesterol synthesis, resulting in low plasma cholesterol levels and raised levels of precursor 7-dehydrocholesterol (7-DHC).[1] The clinical manifestations result from a deficiency in 7-dehydrocholesterol reductase (DHCR-7).[2] In 1964, Dr. Smith, Dr. Lemli, and Dr. Opitz first described the condition based on a case series of 3 male pediatric patients who all presented with common abnormal clinical signs.[3]" /><meta name="og:url" content="https://www.ncbi.nlm.nih.gov/books/NBK599510/" /><meta name="og:site_name" content="NCBI Bookshelf" /><meta name="og:image" content="https://www.ncbi.nlm.nih.gov/corehtml/pmc/pmcgifs/bookshelf/thumbs/th-statpearls-lrg.png" /><meta name="twitter:card" content="summary" /><meta name="twitter:site" content="@ncbibooks" /><meta name="bk-non-canon-loc" content="/books/n/statpearls/article-151214/" /><link rel="canonical" href="https://www.ncbi.nlm.nih.gov/books/NBK599510/" /><link rel="stylesheet" href="/corehtml/pmc/css/figpopup.css" type="text/css" media="screen" /><link rel="stylesheet" href="/corehtml/pmc/css/bookshelf/2.26/css/books.min.css" type="text/css" /><link rel="stylesheet" href="/corehtml/pmc/css/bookshelf/2.26/css/books_print.min.css" type="text/css" /><style type="text/css">p a.figpopup{display:inline !important} .bk_tt {font-family: monospace} .first-line-outdent .bk_ref {display: inline} </style><script type="text/javascript" src="/corehtml/pmc/js/jquery.hoverIntent.min.js"> </script><script type="text/javascript" src="/corehtml/pmc/js/common.min.js?_=3.18"> </script><script type="text/javascript">window.name="mainwindow";</script><script type="text/javascript" src="/corehtml/pmc/js/bookshelf/2.26/book-toc.min.js"> </script><script type="text/javascript" src="/corehtml/pmc/js/bookshelf/2.26/books.min.js"> </script>
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<div class="pre-content"><div><div class="bk_prnt"><p class="small">NCBI Bookshelf. A service of the National Library of Medicine, National Institutes of Health.</p><p>StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2025 Jan-. </p></div></div></div>
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<div class="main-content lit-style" itemscope="itemscope" itemtype="http://schema.org/CreativeWork"><div class="meta-content fm-sec"><h1 id="_NBK599510_"><span class="title" itemprop="name">Smith-Lemli-Opitz Syndrome</span></h1><p class="contrib-group"><h4>Authors</h4><span itemprop="author">Aneil S. Sanghera</span><sup>1</sup>; <span itemprop="author">Marco Zeppieri</span><sup>2</sup>.</p><h4>Affiliations</h4><div class="affiliation"><sup>1</sup> Hull York Medical School</div><div class="affiliation"><sup>2</sup> University Hospital of Udine, Italy</div><p class="small">Last Update: <span itemprop="dateModified">January 11, 2024</span>.</p></div><div class="body-content whole_rhythm" itemprop="text"><div id="article-151214.s1"><h2 id="_article-151214_s1_">Continuing Education Activity</h2><p>Smith-Lemli-Opitz syndrome (SLOS) is an autosomal recessive disorder resulting from an inability to synthesize cholesterol. The syndrome is rare but severe, with an incidence of 1 in 10,000 to 70,000 newborns. Errors in embryogenesis occur due to the lack of cholesterol production, resulting in cell membrane dysfunction and lack of activation of hedgehog proteins responsible for coordinating translocation and differentiation. Further complications result from the continual inability to produce cholesterol and the accumulation of cholesterol precursors.</p><p>The clinical manifestations of SLOS are multisystemic. The presentation affects most organ systems and has a broad spectrum of complications. Most patients with SLOS require lifelong support. Holistic management of patients with this syndrome requires clinicians to understand the pathophysiology and subsequent complications. If recognized, SLOS is closely monitored throughout the patient’s life to avoid further complications and morbidity. This activity describes the epidemiology, genetics, clinical presentation, and management of SLOS, providing healthcare professionals with the knowledge to improve patient care for this complex and prevalent condition.</p><p>
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<b>Objectives:</b>
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<ul><li class="half_rhythm"><div>Determine the pathophysiology of Smith-Lemli-Opitz syndrome.</div></li><li class="half_rhythm"><div>Differentiate the most common physical exam findings associated with Smith-Lemli-Opitz syndrome.</div></li><li class="half_rhythm"><div>Identify the common complications of Smith-Lemli-Opitz syndrome.</div></li><li class="half_rhythm"><div>Implement effective collaboration and communication among interprofessional team members to coordinate comprehensive care and improve patient outcomes.</div></li></ul>
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<a href="https://www.statpearls.com/account/trialuserreg/?articleid=151214&utm_source=pubmed&utm_campaign=reviews&utm_content=151214" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">Access free multiple choice questions on this topic.</a>
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</p></div><div id="article-151214.s2"><h2 id="_article-151214_s2_">Introduction</h2><p>Smith-Lemli-Opitz syndrome (SLOS) is a rare inherited condition characterized by a defect in cholesterol synthesis, resulting in low plasma cholesterol levels and raised levels of precursor 7-dehydrocholesterol (7-DHC).<a class="bk_pop" href="#article-151214.r1">[1]</a> The clinical manifestations result from a deficiency in 7-dehydrocholesterol reductase (DHCR-7).<a class="bk_pop" href="#article-151214.r2">[2]</a> In 1964, Dr. Smith, Dr. Lemli, and Dr. Opitz first described the condition based on a case series of 3 male pediatric patients who all presented with common abnormal clinical signs.<a class="bk_pop" href="#article-151214.r3">[3]</a></p><p>Genetic studies have shown that SLOS has an autosomal recessive pattern of inheritance <a class="bk_pop" href="#article-151214.r4">[4]</a> and is characterized by several features, including syndactyly,<a class="bk_pop" href="#article-151214.r5">[5]</a> microcephaly,<a class="bk_pop" href="#article-151214.r6">[6]</a> growth restriction,<a class="bk_pop" href="#article-151214.r7">[7]</a> intellectual disability,<a class="bk_pop" href="#article-151214.r8">[8]</a> hypospadias (in males),<a class="bk_pop" href="#article-151214.r6">[6]</a> internal abnormalities affecting most organ systems, and other distinctive phenotypical features.<a class="bk_pop" href="#article-151214.r1">[1]</a> White populations have a carrier frequency of 1% to 2%. Discrepancies between the incidence and number of expected cases are attributed to intrauterine death in severe cases and missed diagnosis in mild cases.<a class="bk_pop" href="#article-151214.r9">[9]</a></p></div><div id="article-151214.s3"><h2 id="_article-151214_s3_">Etiology</h2><p>SLOS is a congenital metabolic disorder that follows an autosomal recessive inheritance pattern. The condition is caused by a mutation in the gene that codes for DHCR-7, mapping chromosome location 11q13.<a class="bk_pop" href="#article-151214.r10">[10]</a> Missense mutations are most commonly seen in 87.6% of cases.<a class="bk_pop" href="#article-151214.r11">[11]</a> There are 12 recurring mutations responsible for SLOS, of which the most common in the United States is c.964-1G>C; however, 218 variants have been described.<a class="bk_pop" href="#article-151214.r6">[6]</a><a class="bk_pop" href="#article-151214.r9">[9]</a></p></div><div id="article-151214.s4"><h2 id="_article-151214_s4_">Epidemiology</h2><p>SLOS is most commonly described in European populations. People of Afro-Caribbean, Japanese, East Asian, Korean, and Arabic descent have also been diagnosed.<a class="bk_pop" href="#article-151214.r9">[9]</a><a class="bk_pop" href="#article-151214.r12">[12]</a> The incidence varies in the literature but is estimated at 1 in 10,000 to 70,000 newborns.<a class="bk_pop" href="#article-151214.r13">[13]</a> The greater prevalence in European populations is theorized to be the founder effect.<a class="bk_pop" href="#article-151214.r14">[14]</a> The estimated prevalence of carriers in white populations is between 1% to 2%. The incidence of patients with SLOS is lower due to perinatal mortality in severe cases and underdiagnosis in mild cases.<a class="bk_pop" href="#article-151214.r9">[9]</a></p></div><div id="article-151214.s5"><h2 id="_article-151214_s5_">Pathophysiology</h2><p>In normal physiology, the DHCR-7 gene is responsible for the final step of synthesizing cholesterol, converting 7-DHC to cholesterol. In SLOS, DHCR-7 cannot reduce the 7 to 8 unsaturated bonds found in 7-DHC, resulting in raised levels of 7-DHC and the inability to synthesize cholesterol.<a class="bk_pop" href="#article-151214.r15">[15]</a> About 30% to 50% of the total lipid content in humans is composed of cholesterol, which is essential in the functionality of eukaryotic cell membranes within the body.<a class="bk_pop" href="#article-151214.r9">[9]</a> Cholesterol is the precursor of steroid hormones, oxysterols, vitamin D, and bile acids.<a class="bk_pop" href="#article-151214.r16">[16]</a><a class="bk_pop" href="#article-151214.r17">[17]</a> This is essential in embryogenesis, especially considering that progesterone is responsible for maintaining early pregnancy and further initiating the development of structures such as the neural tube, limbs, brain, and heart.<a class="bk_pop" href="#article-151214.r18">[18]</a> A further important role of cholesterol in embryogenesis is the activation of hedgehog proteins, which are responsible for coordinating cells to translocate and instigate differentiation.<a class="bk_pop" href="#article-151214.r19">[19]</a> Abnormalities in cholesterol production can lead to fetal death or congenital abnormalities.<a class="bk_pop" href="#article-151214.r9">[9]</a><a class="bk_pop" href="#article-151214.r18">[18]</a></p></div><div id="article-151214.s6"><h2 id="_article-151214_s6_">History and Physical</h2><p>SLOS can present with a wide range of clinical features and large phenotypic variation.<a class="bk_pop" href="#article-151214.r1">[1]</a><a class="bk_pop" href="#article-151214.r3">[3]</a> This condition can cause intrauterine death, on fetal anomaly scans, at birth with dysmorphic features, or later in life with neuro-disability.<a class="bk_pop" href="#article-151214.r9">[9]</a> Indications are seen during the antenatal period with increased nuchal translucency and ultrasound findings, which may be able to detect some of the features listed below.<a class="bk_pop" href="#article-151214.r20">[20]</a><a class="bk_pop" href="#article-151214.r21">[21]</a></p><p>Postnatal features can include the following: </p><p>
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<b>Craniofacial Features</b>
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<a class="bk_pop" href="#article-151214.r22">[22]</a>
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</p><ul><li class="half_rhythm"><div>Microcephaly</div></li><li class="half_rhythm"><div>Micrognathia</div></li><li class="half_rhythm"><div>Bilateral ptosis</div></li><li class="half_rhythm"><div>Bitemporal narrowing</div></li><li class="half_rhythm"><div>Cleft palate</div></li><li class="half_rhythm"><div>Short upturned nose</div></li></ul><p>
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<b>Central Nervous System</b>
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<a class="bk_pop" href="#article-151214.r23">[23]</a>
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<a class="bk_pop" href="#article-151214.r24">[24]</a>
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</p><ul><li class="half_rhythm"><div>Hypotonia</div></li><li class="half_rhythm"><div>Hypoplastic or absent corpus callosum</div></li><li class="half_rhythm"><div>Hypoplastic frontal lobes</div></li><li class="half_rhythm"><div>Enlarged ventricles</div></li><li class="half_rhythm"><div>Pituitary lipomas</div></li><li class="half_rhythm"><div>Global developmental delay</div></li><li class="half_rhythm"><div>Learning disability</div></li><li class="half_rhythm"><div>Holoprosencephaly</div></li></ul><p>
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<b>Growth and Skeletal</b>
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<a class="bk_pop" href="#article-151214.r25">[25]</a>
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</p><ul><li class="half_rhythm"><div>Delay in growth</div></li><li class="half_rhythm"><div>Restricted growth in utero</div></li><li class="half_rhythm"><div>Abnormal fingerprints</div></li><li class="half_rhythm"><div>Postaxial polydactyl</div></li><li class="half_rhythm"><div>Syndactyly</div></li></ul><p>
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<b>Genital</b>
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<a class="bk_pop" href="#article-151214.r26">[26]</a>
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</p><ul><li class="half_rhythm"><div>Ambiguous genitalia</div></li><li class="half_rhythm"><div>Hypospadias</div></li><li class="half_rhythm"><div>Sex reversal</div></li></ul><p>
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<b>Cardiovascular</b>
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<a class="bk_pop" href="#article-151214.r27">[27]</a>
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</p><ul><li class="half_rhythm"><div>Ostium primum</div></li><li class="half_rhythm"><div>Atrial septal defect</div></li><li class="half_rhythm"><div>Ventricular septal defects</div></li><li class="half_rhythm"><div>Patent ductus arteriosus</div></li><li class="half_rhythm"><div>Atrioventricular canal </div></li></ul><p>
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<b>Renal and Adrena</b>
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<a class="bk_pop" href="#article-151214.r28">[28]</a>
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</p><ul><li class="half_rhythm"><div>Adrenal hypo/hyperplasia</div></li><li class="half_rhythm"><div>Renal ectopia</div></li><li class="half_rhythm"><div>Renal aplasia/hypoplasia</div></li><li class="half_rhythm"><div>Renal cortical cysts</div></li><li class="half_rhythm"><div>Ureteral duplication</div></li><li class="half_rhythm"><div>Underdeveloped external genitalia and hypospadias (males)</div></li></ul><p>
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<b>Respiratory</b>
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<a class="bk_pop" href="#article-151214.r29">[29]</a>
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</p><ul><li class="half_rhythm"><div>Abnormalities of the tracheal and laryngeal cartilage</div></li><li class="half_rhythm"><div>Pulmonary hypoplasia</div></li><li class="half_rhythm"><div>Abnormal pulmonary lobation</div></li></ul><p>
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<b>Gastroenterology</b>
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<a class="bk_pop" href="#article-151214.r30">[30]</a>
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</p><ul><li class="half_rhythm"><div>Gastroesophageal reflux disease (GERD)</div></li><li class="half_rhythm"><div>Pyloric stenosis</div></li><li class="half_rhythm"><div>Hirschprung disease</div></li><li class="half_rhythm"><div>Intestinal dysmotility</div></li><li class="half_rhythm"><div>Cholestatic liver disease</div></li></ul></div><div id="article-151214.s7"><h2 id="_article-151214_s7_">Evaluation</h2><p>The evaluation of SLOS begins antenatally. Ultrasound scans during pregnancy can show evidence of fetal anomalies. Antenatal diagnosis is further suggested by multimarker screening tests, which can indicate possible abnormalities in the presence of low unconjugated estriol levels, mildly depressed alfa fetoprotein, and low levels of human chorionic gonadotropin.<a class="bk_pop" href="#article-151214.r1">[1]</a><a class="bk_pop" href="#article-151214.r31">[31]</a> Gas chromatography-mass spectrometry can be used during pregnancy to test maternal urine and to give a reliable diagnosis of SLOS noninvasively, eliminating the need for amniotic sampling.<a class="bk_pop" href="#article-151214.r32">[32]</a><a class="bk_pop" href="#article-151214.r33">[33]</a> Prenatal abnormalities can lead to a raised level of 7-DHC or an increased ratio of 7-dehydropregnanetriol/pregnanetriol, due to the fetal inability to reduce the double bond seen in the 7th position.<a class="bk_pop" href="#article-151214.r34">[34]</a> Prenatal screening tests can show increased nuchal translucency on antenatal scans and other signs of fetal growth alterations. Postnatally, SLOS should be included in the differential diagnosis in the presence of altered phenotypical features.</p><p>Serum cholesterol levels cannot be used to diagnose SLOS, considering that 10% of cases have a normal serum cholesterol level. Furthermore, patients with SLOS can have a normal cholesterol level as cholesterol assay testing can fail to distinguish between 7-DHC and cholesterol, leading to falsely raised levels.<a class="bk_pop" href="#article-151214.r1">[1]</a><a class="bk_pop" href="#article-151214.r21">[21]</a> Raised levels of 7-DHC and 8-DHC are used instead in suspected cases, and diagnosis is confirmed with DHCR-7 mutation analysis.<a class="bk_pop" href="#article-151214.r21">[21]</a><a class="bk_pop" href="#article-151214.r32">[32]</a> The classification is based on the modified Bialer scoring system, which uses separate embryological systems to score the severity of the syndrome.<a class="bk_pop" href="#article-151214.r3">[3]</a> The score is based on the clinical conditions of the brain, oral apparatus, acral, eye, heart, kidney, liver, lung, bowel, and genitalia. The scores in each domain are on a scale of 0 to 2, with a higher score indicating a more severe presentation. </p></div><div id="article-151214.s8"><h2 id="_article-151214_s8_">Treatment / Management</h2><p>There are no consensus clinical guidelines for treating and managing SLOS. The mainstay of treatment usually consists of supplementation with dietary cholesterol and oral bile acid therapy, which are needed to increase serum cholesterol levels to improve signs and symptoms.<a class="bk_pop" href="#article-151214.r35">[35]</a> Treatment aims to improve the development, growth, and behavioral difficulties of SLOS.<a class="bk_pop" href="#article-151214.r1">[1]</a><a class="bk_pop" href="#article-151214.r21">[21]</a> These include poor sleep and the severity of autism spectrum disorder (although no randomized controlled trials demonstrate the effectiveness).<a class="bk_pop" href="#article-151214.r36">[36]</a><a class="bk_pop" href="#article-151214.r37">[37]</a></p><p>The limitation of cholesterol supplementation is the inability to cross the blood-brain barrier. Further supportive care is recommended in the form of nasogastric feeding or gastrostomy. Routine surveillance is required in all patients. Surgical interventions may be necessary for some of the abnormalities commonly seen in SLOS. They support quality of life and depend on the clinical manifestations in each patient.</p><p>Special considerations are made when planning surgical intervention on patients with SLOS, considering that these patients can have difficulties during intubation due to laryngotracheal malformations and are at risk of malignant hyperthermia.<a class="bk_pop" href="#article-151214.r36">[36]</a><a class="bk_pop" href="#article-151214.r38">[38]</a> Psychosocial support should be offered to families, including genetic counseling for future pregnancies. </p></div><div id="article-151214.s9"><h2 id="_article-151214_s9_">Differential Diagnosis</h2><p>The differential diagnosis of SLOS is broad and includes several syndromes with a multisystemic impact. These conditions have overlapping dysmorphic features, making clinical diagnosis difficult.<a class="bk_pop" href="#article-151214.r39">[39]</a> These include but are not limited to:<a class="bk_pop" href="#article-151214.r40">[40]</a><a class="bk_pop" href="#article-151214.r41">[41]</a> </p><ul><li class="half_rhythm"><div>Gardner-Silengo-Wachtel syndrome (Genito-Palato-Cardiac syndrome)<a class="bk_pop" href="#article-151214.r42">[42]</a></div></li><li class="half_rhythm"><div>Young Madders syndrome (Pseudotrisomy 13/Holoprosencephaly–Polydactyly syndrome)<a class="bk_pop" href="#article-151214.r43">[43]</a></div></li><li class="half_rhythm"><div>Patau syndrome (trisomy 13)<a class="bk_pop" href="#article-151214.r44">[44]</a></div></li><li class="half_rhythm"><div>Noonan syndrome<a class="bk_pop" href="#article-151214.r45">[45]</a></div></li><li class="half_rhythm"><div>Opitz G (BBB syndrome)<a class="bk_pop" href="#article-151214.r46">[46]</a></div></li><li class="half_rhythm"><div>Edwards syndrome (trisomy 18)<a class="bk_pop" href="#article-151214.r47">[47]</a></div></li><li class="half_rhythm"><div>Zellweger syndrome<a class="bk_pop" href="#article-151214.r48">[48]</a></div></li><li class="half_rhythm"><div>Pierre Robin sequence<a class="bk_pop" href="#article-151214.r49">[49]</a></div></li></ul></div><div id="article-151214.s10"><h2 id="_article-151214_s10_">Pertinent Studies and Ongoing Trials</h2><p>Limited research is available on SLOS as recruitment to trials is difficult due to the low incidence rate. There is ongoing research into statins' efficacy in treating SLOS. Statins are theorized to benefit patients with SLOS by reducing the precursor build-up of 7-DHC; however, current studies suggest limited benefit on quality of life or survival.<a class="bk_pop" href="#article-151214.r50">[50]</a> Antioxidants such as Vitamin E are tested in animal studies, which may benefit in minimizing the harmful effects associated with the accumulation of 7-DHC.<a class="bk_pop" href="#article-151214.r51">[51]</a> </p></div><div id="article-151214.s11"><h2 id="_article-151214_s11_">Prognosis</h2><p>The prognosis is variable depending on the severity of the disease. Severe cases can result in fetal death in utero, while some milder cases can survive into adulthood with minimal effects.<a class="bk_pop" href="#article-151214.r36">[36]</a> Of those that survive past the neonatal period, there is a 20% mortality rate in the first year of life, and generally, life expectancies are shortened.<a class="bk_pop" href="#article-151214.r2">[2]</a> The leading cause of death in SLOS during infancy is gastrointestinal disorders leading to malnutrition, alongside sudden causes such as infection, hypoglycemia, and adrenal insufficiency.<a class="bk_pop" href="#article-151214.r52">[52]</a> Most patients tend to require ongoing support throughout their lives due to developmental delay and intellectual disability. </p></div><div id="article-151214.s12"><h2 id="_article-151214_s12_">Complications</h2><p>Complications can impact numerous organs and tissues in SLOS. Gastrointestinal complications can be related to gastroesophageal reflux disease and hypotonia, resulting in delayed transit and dysmotility. Patients can also experience further feeding problems due to poor sucking reflex or swallowing coordination, which require artificial feeding, gastrostomy, and surgical interventions such as fundoplication.<a class="bk_pop" href="#article-151214.r1">[1]</a> Pyloric stenosis and Hirschprung disease are also documented as complications.<a class="bk_pop" href="#article-151214.r15">[15]</a> </p><p>There is a range of intellectual disabilities, with most children having low IQ. However, normal or low-normal IQ is possible.<a class="bk_pop" href="#article-151214.r53">[53]</a> There is a strong association between SLOS and autism spectrum disorder. Classical behaviors are variable by age. Infants are difficult to settle, while older children are characterized by throwing the upper body backward, aggressive behaviors, sleep disturbances, and self-harming behaviors such as headbanging.<a class="bk_pop" href="#article-151214.r54">[54]</a><a class="bk_pop" href="#article-151214.r55">[55]</a> Approximately 75% of patients with SLOS develop autism spectrum disorder (ASD).<a class="bk_pop" href="#article-151214.r56">[56]</a> </p><p>Renal abnormalities such as renal agenesis, hypoplasia, and hydronephrosis are expected, with an incidence rate of 43%.<a class="bk_pop" href="#article-151214.r3">[3]</a> A further 44% of patients are born with cardiovascular defects, most commonly atrial septal defects (ASDs) and atrioventricular septal defects (AVSDs).<a class="bk_pop" href="#article-151214.r57">[57]</a> Heart failure and chronic renal failure can arise from these abnormalities.</p></div><div id="article-151214.s13"><h2 id="_article-151214_s13_">Deterrence and Patient Education</h2><p>Genetic counseling for parents with children who have SLOS is important to explain the mode of inheritance. This can help support their decision for genetic testing and considerations for future family planning. Further counseling can be provided to educate parents on the potential outcomes of pregnancy with suspected SLOS, including preparing parents for perinatal death and resuscitation. Parents need to be given pertinent information about this condition, which can help them make informed decisions for children with this disorder.</p></div><div id="article-151214.s14"><h2 id="_article-151214_s14_">Pearls and Other Issues</h2><ul><li class="half_rhythm"><div>SLOS is a rare condition with an autosomal recessive pattern of inheritance.</div></li><li class="half_rhythm"><div>The syndrome is multi-malformation with a wide range of clinical features.</div></li><li class="half_rhythm"><div>Clinical diagnosis is complex and can be supported with genetic and biochemical testing of precursors (7-DHC & 8-DHC).</div></li><li class="half_rhythm"><div>Management is with a high-cholesterol diet; however, no definitive treatment exists.</div></li><li class="half_rhythm"><div>Of those surviving the neonatal period, 20% die within the first year of life. </div></li></ul></div><div id="article-151214.s15"><h2 id="_article-151214_s15_">Enhancing Healthcare Team Outcomes </h2><p>A multidisciplinary approach is recommended in managing SLOS, and given its varying clinical manifestations, several teams working collaboratively are required to optimize patient care.</p><ul><li class="half_rhythm"><div>Neonatologists and general pediatricians are recommended for acute management at birth and throughout childhood.</div></li><li class="half_rhythm"><div>Geneticists help confirm the diagnosis and provide counseling for parents.<a class="bk_pop" href="#article-151214.r1">[1]</a></div></li><li class="half_rhythm"><div>Gastroenterologists, dieticians, and speech and language therapists are involved in supporting the nutrition of these patients.<a class="bk_pop" href="#article-151214.r58">[58]</a></div></li><li class="half_rhythm"><div>Occupational therapists and physiotherapists provide support by helping with developmental delays and providing adaptations to improve patient's quality of life.<a class="bk_pop" href="#article-151214.r1">[1]</a> </div></li><li class="half_rhythm"><div>Nurses support patients during acute admissions, helping administer medications, noting observations, and training parents to use nasogastric tubes.</div></li><li class="half_rhythm"><div>Depending on the severity of the cardiac, renal, ophthalmological, and neurological structural abnormalities, you might expect involvement from each of the teams above. Surgical teams, particularly maxillary facial teams, are consulted for craniofacial anomalies.<a class="bk_pop" href="#article-151214.r1">[1]</a> </div></li><li class="half_rhythm"><div>Radiologists play an important role in planning and interpreting scans in most patients, providing critical information to support decision-making.</div></li><li class="half_rhythm"><div>Audiologists are required if there is a degree of hearing impairment.</div></li><li class="half_rhythm"><div>Pharmacists are utilized to optimize medications.<a class="bk_pop" href="#article-151214.r1">[1]</a> </div></li><li class="half_rhythm"><div>Neuropsychiatric clinicians play a role in diagnosing autism and helping manage challenging behaviors.</div></li><li class="half_rhythm"><div>Palliative care clinicians may be involved in patients with SLOS due to the complex care and shortened life span.</div></li></ul><p>A team effort from medical professionals, including doctors, advanced practice nurses, pharmacists, and others, provides patient-centered care for people with SLOS. Adopting a strategic approach with customized care plans based on each patient's particular needs is essential.</p><p>Choosing a course of treatment involves ethical issues. Each interprofessional team member should contribute their specific knowledge and abilities to optimize patient care, with clearly defined roles and responsibilities. Effective interprofessional communication fosters a collaborative environment where information is shared, questions are welcomed, and concerns are addressed.</p><p>Care coordination is essential to guarantee smooth and effective patient care. To optimize the patient experience, from diagnosis to treatment and follow-up, healthcare professionals such as physicians, advanced practitioners, nurses, pharmacists, and others must collaborate. The well-being and contentment of individuals impacted by SLOS are prioritized in patient-centered care, which improves results and leads to fewer mistakes, shorter wait times, and increased patient safety.</p></div><div id="article-151214.s16"><h2 id="_article-151214_s16_">Review Questions</h2><ul><li class="half_rhythm"><div>
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</div></li></ul></div><div id="article-151214.s17"><h2 id="_article-151214_s17_">References</h2><dl class="temp-labeled-list"><dt>1.</dt><dd><div class="bk_ref" id="article-151214.r1">Nowaczyk MJM, Wassif CA. Smith-Lemli-Opitz Syndrome. In: Adam MP, Feldman J, Mirzaa GM, Pagon RA, Wallace SE, Amemiya A, editors. <span class="ref-journal">GeneReviews<sup>®</sup> [Internet].</span> University of Washington, Seattle; Seattle (WA): Nov 13, 1998. [<a href="https://pubmed.ncbi.nlm.nih.gov/20301322" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 20301322</span></a>]</div></dd><dt>2.</dt><dd><div class="bk_ref" id="article-151214.r2">Gedam R, Shah I, Ali U, Ohri A. 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Development, behavior, and biomarker characterization of Smith-Lemli-Opitz syndrome: an update. <span><span class="ref-journal">J Neurodev Disord. </span>2016;<span class="ref-vol">8</span>:12.</span> [<a href="/pmc/articles/PMC4822234/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC4822234</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/27053961" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 27053961</span></a>]</div></dd></dl></div><div><dl class="temp-labeled-list small"><dt></dt><dd><div><p class="no_top_margin">
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<b>Disclosure: </b>Aneil Sanghera declares no relevant financial relationships with ineligible companies.</p></div></dd><dt></dt><dd><div><p class="no_top_margin">
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<b>Disclosure: </b>Marco Zeppieri declares no relevant financial relationships with ineligible companies.</p></div></dd></dl></div></div></div>
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