Smith-Lemli-Opitz Syndrome

2017 ◽  
Author(s):  
Ryan W. Lee
Keyword(s):  
Congenital Anomaly ◽  
Inborn Error ◽  
Cholesterol Synthesis ◽  
Plasma Cholesterol ◽  
Autism Spectrum ◽  
Behavioral Phenotype ◽  
Facial Features ◽  
Multiple Congenital Anomaly ◽  
Opitz Syndrome

Smith-Lemli-Opitz syndrome (OMIM 270400) (SLOS) is a multiple congenital anomaly disorder caused by an inborn error of cholesterol synthesis. Studies demonstrated that mutations in the gene for 3b-hydroxysterol-D7 reductase (DHCR7) result in low plasma cholesterol and corresponding increases in 7DHC. Distinctive facial features of include ptosis, small nose with anteverted nares, and micrognathia. Acral dysgenesis is common, foremost of which involve syndactyly and polydactyly. Children with SLOS often have a behavioral phenotype within the autism spectrum.

Biochemical Abnormality Associated with Smith-Lemli-Opitz Syndrome in an Infant with Features of Rutledge Multiple Congenital Anomaly Syndrome Confirms that the Latter is a Variant of the Former

2003 ◽  
Vol 6 (3) ◽  
pp. 270-277 ◽  
Author(s):  
Dinesh Rakheja ◽  
Golder N. Wilson ◽  
Beverly B. Rogers
Keyword(s):  
Congenital Anomaly ◽  
Liver Tissue ◽  
Hirschsprung Disease ◽  
Mendelian Inheritance ◽  
Severe Form ◽  
Appendicular Skeleton ◽  
Multiple Congenital Anomaly ◽  
Nasal Bridge ◽  
Opitz Syndrome ◽  
The Right

We describe a female infant with morphologic features of Rutledge multiple-congenital-anomaly syndrome (RM-CAS) and biochemical features of Smith-Lemli-Opitz syndrome (SLOS). She had microcephaly with hypoplastic cerebral frontal lobes and cerebellum, agenesis of the splenium of corpus callosum, abnormal facies including hypertelorism with bilateral inner epicanthal folds, a broad nasal bridge with slightly anteverted nares and patent choanae, low set ears and complex conchal formation, high-arched palate and thick maxillary alveolar ridges, and micrognathia. Her chest was broad, genitalia were ambiguous, and uterus was bicornuate. Skeletal abnormalities included a hypoplastic appendicular skeleton, post-axial hexadactyly of the right hand and the left foot, syndactyly of bilateral 2nd–3rd toes and left 5th–6th toes, right talipes varus and left talipes valgus, and fused L5–S1 vertebrae. Congenital heart disease consisted of hypoplastic left heart, coronary sinus agenesis, ostium secundum and ostium primum defects, and a thickened septum primum. The lungs were hypolobated and the kidneys manifested oligopapillary hypoplasia. Total colonic Hirschsprung disease was noted microscopically. Analysis of liver tissue taken at postmortem examination revealed the ratio of 7-dehydrocholesterol and cholesterol to be 143 (expected, 0.28 ± 0.28). Although initially described as a distinct syndrome, RMCAS was merged with the severe form of SLOS, because of significantly overlapping features [Online Mendelian Inheritance in Man (OMIM) #268670]. The biochemical data showing an excess of 7-dehydrocholesterol and low cholesterol in the liver tissue of our case supports this viewpoint.

Lower Lip Pits: Van der Woude or Kabuki Syndrome?

2014 ◽  
Vol 51 (6) ◽  
pp. 729-734 ◽  
Author(s):  
Ferri P. David-Paloyo ◽  
Xuecai Yang ◽  
Ju-Li Lin ◽  
Fen-Hwa Wong ◽  
Yah-Huei Wu-Chou ◽  
...  
Keyword(s):  
Congenital Anomaly ◽  
Mental Retardation ◽  
Clinical Spectrum ◽  
Facial Features ◽  
Kabuki Syndrome ◽  
Multiple Congenital Anomaly ◽  
Van Der Woude Syndrome ◽  
Lower Lip ◽  
Long Term Prognosis

Kabuki syndrome (KS) is a multiple congenital anomaly/mental retardation syndrome with characteristic facial features. Despite more than 350 documented cases and recent correlation of MLL2 mutations as a genetic cause, its full clinical spectrum is still being defined. This report describes two patients who were initially diagnosed with Van der Woude syndrome (VWS) based on the presence of lower lip pits. However, this finding can occur with KS, albeit infrequently. For patients with lower lip pits, a thorough evaluation should be made to distinguish between VWS and KS, as there are differences in long-term prognosis.

scholarly journals Esophageal Perforation in a Patient with Smith-Lemli-Opitz Syndrome

2020 ◽  
pp. 1-3
Author(s):  
Irim Salik ◽  
Irim Salik ◽  
Jasmeet Easwar
Keyword(s):  
Esophageal Perforation ◽  
Inborn Error ◽  
Congenital Heart ◽  
Cholesterol Metabolism ◽  
Clinical Manifestations ◽  
Facial Features ◽  
Difficult Airway Management ◽  
Esophageal Foreign Body ◽  
Severe Intellectual Disability ◽  
Opitz Syndrome

Smith-Lemli-Opitz syndrome (SLOS) is a rare syndrome caused by an inborn error of cholesterol metabolism secondary to a deficiency in the 7-dehydrocholesterol (7-DHC) reductase enzyme leading to hypocholesterolemia. A broad spectrum of clinical manifestations can have significant surgical and anaesthetic implications. Patients exhibit growth retardation, microcephaly, congenital heart disease and moderate to severe intellectual disability. Distinctive facial features including micrognathia, cleft palate and prominent incisors can lead to difficult airway management [1]. We present the case of a 16-year-old female with SLOS who developed an esophageal perforation following esophageal foreign body retrieval. Anaesthetic and surgical considerations in a patient with SLOS are discussed.

Smith-Lemli-Opitz syndrome with extremely low plasma cholesterol

2000 ◽  
Vol 23 (6) ◽  
pp. 638-639 ◽  
Author(s):  
V. Bzdúch ◽  
D. Behúlová ◽  
L. Kozák ◽  
J. Škodová ◽  
E. Véghová ◽  
...  
Keyword(s):  
Plasma Cholesterol ◽  
Opitz Syndrome

scholarly journals Juvenile Shank3b deficient mice present with behavioral phenotype relevant to autism spectrum disorder

2019 ◽  
Vol 356 ◽  
pp. 137-147 ◽  
Author(s):  
Chantell Balaan ◽  
Michael J. Corley ◽  
Tiffany Eulalio ◽  
Ka’ahukane Leite-ahyo ◽  
Alina P.S. Pang ◽  
...  
Keyword(s):  
Autism Spectrum Disorder ◽  
Autism Spectrum ◽  
Behavioral Phenotype ◽  
Spectrum Disorder ◽  
Deficient Mice

scholarly journals Behavioral phenotype and autism spectrum disorders in Cornelia de Lange syndrome

2015 ◽  
Vol 7 (2) ◽  
Author(s):  
Lucia Parisi ◽  
Teresa Di Filippo ◽  
Michele Roccella
Keyword(s):  
Behavioral Problems ◽  
Developmental Trajectories ◽  
Point Mutations ◽  
Autism Spectrum ◽  
Behavioral Phenotype ◽  
Repetitive Behaviors ◽  
Cornelia De Lange Syndrome ◽  
Impulsive Behavior ◽  
Self Injury ◽  
Cornelia De Lange

Cornelia de Lange syndrome (CdLS) is a congenital disorder characterized by distinctive facial features, growth retardation, limb abnormalities, intellectual disability, and behavioral problems. Cornelia de Lange syndrome is associated with abnormalities on chromosomes 5, 10 and X. Heterozygous point mutations in three genes (<em>NIPBL</em>, <em>SMC3</em> and <em>SMC1A</em>), are responsible for approximately 50-60% of CdLS cases. CdLS is characterized by autistic features, notably excessive repetitive behaviors and expressive language deficits. The prevalence of autism spectrum disorder (ASD) symptomatology is comparatively high in CdLS. However, the profile and developmental trajectories of these ASD characteristics are potentially different to those observed in individuals with idiopathic ASD. A significantly higher prevalence of self-injury are evident in CdLS. Self-injury was associated with repetitive and impulsive behavior. This study describes the behavioral phenotype of four children with Cornelia de Lange syndrome and ASDs and rehabilitative intervention that must be implemented.

scholarly journals Non-cell autonomous inhibition of the Shh pathway due to impaired cholesterol biosynthesis requires Ptch1/2

2020 ◽  
Author(s):  
Carian Jägers ◽  
Henk Roelink
Keyword(s):  
Sonic Hedgehog ◽  
Birth Defects ◽  
Cholesterol Synthesis ◽  
Cholesterol Biosynthesis ◽  
Shh Signaling ◽  
Shh Pathway ◽  
Opitz Syndrome ◽  
Cholesterol Precursors ◽  
G Protein Coupled ◽  
Mutant Cells

AbstractBirth defects due to congenital errors in enzymes involved cholesterol synthesis like Smith-Lemli-Opitz syndrome (SLOS) and Lathosterolosis cause an accumulation of cholesterol precursors and a deficit in cholesterol. The phenotype of both SLOS and Lathosterolosis have similarities to syndromes associated with abnormal Sonic hedgehog (Shh) signaling, consistent with the notion that impaired cholesterol signaling can cause reduced Shh signaling. Two multipass membrane proteins play central roles in Shh signal transduction, the putative Resistance, Nodulation and Division (RND) antiporters Ptch1 and Ptch2, and the G-protein coupled receptor Smoothened (Smo). Sterols have been suggested as cargo for Ptch1, while Smo activity can affected both positively and negatively by steroidal molecules. We demonstrate that mESCs mutant for 7-dehydroxycholesterol reductase (7dhcr) or sterol-C5-desaturase (sc5d) reduce the Hh response in nearby wildtype cells when grown in mosaic organoids. This non-cell autonomous inhibitory activity of the mutant cells required the presence of both Ptch1 and Ptch2. These observations support a model in which late cholesterol precursors that accumulate in cells lacking 7DHCR are the cargo for Ptch1 and Ptch2 activity that mediates the non-cell autonomous inhibition of Smo.

scholarly journals Hypothesis: The Role of Sterols in Autism Spectrum Disorder

2011 ◽  
Vol 2011 ◽  
pp. 1-7 ◽  
Author(s):  
Ryan W. Y. Lee ◽  
Elaine Tierney
Keyword(s):  
Autism Spectrum Disorder ◽  
Sonic Hedgehog ◽  
Autism Spectrum ◽  
Membrane Lipid ◽  
Molecular Techniques ◽  
Spectrum Disorder ◽  
Advanced Imaging ◽  
Opitz Syndrome ◽  
Membrane Physiology

A possible role for sterols in the development of autism spectrum disorder (ASD) has not been proven, but studies in disorders of sterol biosynthesis, chiefly Smith-Lemli-Opitz syndrome (SLOS), enable hypotheses on a causal relationship to be discussed. Advances in genetic technology coupled with discoveries in membrane physiology have led to renewed interest for lipids in the nervous system. This paper hypothesizes on the role of sterol dysfunction in ASD through the framework of SLOS. Impaired sonic hedgehog patterning, alterations in membrane lipid rafts leading to abnormal synaptic plasticity, and impaired neurosteroid synthesis are discussed. Potential therapeutic agents include the development of neuroactive steroid-based agents and enzyme-specific drugs. Future investigations should reveal the specific mechanisms underlying sterol dysfunction in neurodevelopmental disorders by utilizing advanced imaging and molecular techniques.

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