Clinical features and genetic testing of a Chinese pedigree affected with Smith-Lemli-Opitz syndrome / 中华医学遗传学杂志

OBJECTIVE@#To analyze the clinical features and genetic variants of two patients from a pedigree affected with Smith-Lemli-Opitz syndrome and explore their genotype-phenotype correlation.@*METHODS@#Clinical data and family history of the pedigree were collected. Whole exome sequencing was carried out to identify the potential variants. Suspected variants were verified by Sanger sequencing of the family members.@*RESULTS@#The proband and her sister both presented with feeding difficulty, facial dysmorphism, seizures, and mental and speech retardation. The third child of this family presented with feeding difficulty, poor weight gain and severe malnutrition after birth. He had died of unknown cause at 6 months without genetic testing. The fourth child was a healthy boy. Genetic testing showed that both the proband and her sister have carried c.127G>T (p.Val43Phe) and c.820_825del (p.Asn274_Val275del) compound heterozygous variants of the DHCR7 gene (NM_001360.2), but the fourth child carried neither of the variants. The two variants were unreported in the literature and disease-related databases, and were not included in the 1000G and gnomAD databases. The c.820_825del variant may affect the sterol-sensitive region of the DHCR7 protein, which can lead to deletion of two amino acids at positions 247 and 275, causing truncation of the DHCR7 protein. It is speculated that this may affect the stability of protein's spatial conformation, thereby decrease the activity of the enzyme. The c.127G>T variant may affect the first transmembrane region of the protein, which is involved in the transmembrane transport of proteins. Multiple software predicted it to be harmful. Conservation analysis suggested that the three amino acids all locate in a highly conserved region of the protein. In consideration of the clinical phenotype, family history and result of genetic testing, we speculated that both patients had Smith-Lemli-Opitz syndrome due to variants of the DHCR7 gene.@*CONCLUSION@#This pedigree has enriched the phenotypic and genotypic data of Smith-Lemli-Opitz syndrome, which clarified the genetic etiology of the patients and provided a basis for genetic counseling of this pedigree.

Clinical and genetic analysis of a Chinese pedigree affected with Smith-Lemli-Opitz syndrome / 中华医学遗传学杂志

OBJECTIVE@#To explore the clinical phenotype and pathogenic variants in a Chinese pedigree affected with Smith-Lemli-Opitz syndrome.@*METHODS@#Peripheral blood samples were collected from five members, including two affected ones, from the pedigree for the extraction of genomic DNA. Whole exome sequencing was carried out, and candidate variants were verified by Sanger sequencing as well as reverse transcription sequencing at the RNA level.@*RESULTS@#The proband and another affected child from the pedigree showed mental retardation, dyskinesia, microcephaly, micrognathia, anteverted nares, and 2/3 toe syndactyly. The proband also had hypospadia, single upper incisor, and lower serum cholesterol level. Both children were found to harbor a paternally derived c.278C>T (p.T93M) variant and a maternally derived c.907G>A (p.G303R) variant of the DHCR7 gene. Both were known pathogenic mutations.@*CONCLUSION@#The compound heterozygous mutations of c.278C>T (p.T93M) and c.907G>A (p.G303R) of the DHCR7 gene probably underlay the disease in this pedigree. Above finding has enabled early diagnosis and treatment of Smith-Lemli-Opitz syndrome.

Síndrome de Smith-Lemli-Opitz e hipotiroidismo: el primer caso venezolano / Smith-Lemli-Opitz syndrome and hypothyroidism: the first Venezuelan case

El síndrome de Smith-Lemli-Opitz (SSLO) es un desorden metabólico autosómico recesivo debido a la síntesis anormal de colesterol y fue descrito por primera vez por Smith, Lemli y Opitz en 1964. Muchos casos de SSLO han sido descritos desde entonces, siendo reconocido como un síndrome malformativo relativamente común. Los individuos afectados tienen dismorfismo, microcefalia, múltiples malformaciones congénitas, retraso mental, agresividad e hiperactividad. La severidad de los defectos físicos se correlaciona con la severidad de la deficiencia de colesterol, la cual es causada por la baja actividad de la 7-dehidrocolesterol reductasa, enzima responsable de la conversión de 7-dehidrocolesterol a colesterol. La ocurrencia de hipotiroidismo en asociación con SSLO es muy inusual. Este constituye el primer caso venezolano en el que se asocian ambas patologías.

The Smith-Lemli-Opitz syndrome (SLOS) is an autosomal recessive metabolic disorder due to an abnormal cholesterol synthesis. It was first described by Smith, Lemli and Opitz in 1964. Many cases of SLOS have been described since then, leading to the recognition as a relatively common malformation syndrome. Affected individuals have dysmorphism, microcephaly, multiple congenital malformations, mental retardation, aggressiveness and hyperactivity. The severity of physical defects correlates with the severity of the cholesterol deficiency, which is caused by an abnormally low activity of 7-dehydrocholesterol reductase, the enzyme responsible for conversion of 7-dehydrocholesterol to cholesterol. The occurrence of hypothyroidism in association with SLOS is very unusual. We describe the first Venezuelan case in which both anomalies are associated.

Modificação de proteínas por produtos de oxidação do colesterol: mecanismos e implicações biológicas / Modification of proteins by oxidation products of cholesterol: mechanisms and biological implications

O colesterol é um importante componente das membranas celulares em eucariotos superiores, desempenhando papéis estruturais e funcionais. O colesterol possui uma insaturação em sua estrutura sendo, portanto, alvo de oxidação mediada por espécies reativas de oxigênio e/ou nitrogênio. A oxidação não enzimática do colesterol gera, como produtos primários, os hidroperóxidos de colesterol. Tais moléculas, por sua vez, são altamente reativas e podem reagir com metais livres e/ou metaloproteínas, trazendo consequências à celula. Neste sentido, o primeiro capítulo deste trabalho tem como objetivo estudar a reação dos hidroperóxidos de colesterol (ChOOH) com o citocromo c (citc), uma heme proteína envolvida no transporte de elétrons na mitocôndria. Análises de espectroscopia no UV-Vis mostraram que o ChOOH promove o bleaching da banda Soret do citc de uma maneira dose-dependente. Mais ainda, esta reação leva à formação de radicais centrados em carbono tanto na proteína como no lipídeo, sugerindo uma redução homolítica do ChOOH. Como consequências, pode-se observar a oligomerização do citc, um processo que pode influenciar no transporte de elétrons bem como na sinalização para a apoptose. A partir da reação do citc com ChOOH podem surgir, direta ou indiretamente, outras espécies reativas, como aldeídos, cetonas e epóxidos. Dentre estas, destacam-se os aldeídos de colesterol, em particular o colesterol secoaldeído (CSec) e o carboxialdeído (ChAld), uma vez que foram encontrados elevados em placas ateroscleróticas e em tecidos cerebrais de pacientes com doenças neurodegenerativas. Tais espécies podem reagir com resíduos de aminoácidos provocando alterações estruturais e funcionais em proteínas. Neste sentido, o segundo capítulo deste trabalho tem como objetivo estudar a reação do ChAld com citc. Usando modelos mimétivos de membrana e espectrometria de massas, foi mostrado que o ChAld modifica covalentemente o citc por um mecanismo consistente com a formação de bases de Schiff. Tal modificação ocorre preferencialmente em resíduos de lisina que interagem com a membrana. Estas modificações influenciam na afinidade do citc pela membrana, aumentando sua aderência, o que pode ter influência no transporte de elétrons e sinalização para a apoptose. No terceiro e último capítulo deste trabalho nós buscamos uma ferramente analítica que permitisse analisar modificação de proteínas promovidas por produtos de oxidação de colesterol e outros esteróis. Em um estudo realizado em colaboração com o grupo do professor Porter na Universidade de Vanderbilt, utilizamos ensaios baseados em click chemistry para buscar proteínas modificadas. Para isso, foram sintetizados derivados de colesterol e 7-deidrocolesterol (7-DHC, precursor imediato do colesterol) contendo um grupo alquinil na sua cadeia lateral. Este grupo pode ser ligado a um grupo azida por meio de uma reação de cicloadição, em um processo conhecido como click chemistry. Após a síntese e caracterização dos derivados lipídicos contendo o grupo alquinil na cadeia lateral, células Neuro2a foram tratadas com o alquinil-7-DHC e o alquinil-colesterol para averiguar seu metabolismo. Análises por HPLC-MS/MS mostraram que ambos derivados contendo o grupo alquinil foram metabolisados e convertdos nos respectivos ésteres. Usando um modelo celular para a doença conhecida como Sindrome de Smith-Lemli-Opitz (SLOS), doença caracterizada pela deficiência na enzima 7-deidrocolesterol redutase, foi mostrado que o acúmulo característico de 7-DHC nos pacientes pode levar a uma maior modificação de proteínas promovidas por seus derivados, o que pode contribuir para o desenvolvimento da doença

Cholesterol is an important component of eukaryotic cellular membranes, where it has an influence in the fluidity and stability. Due to the presence of a double bond in its structure, cholesterol can be oxidized by reactive oxygen and nitrogen species. This non-enzymatic oxidation generates, as primary products, cholesterol hydroperoxides. Such molecules, in turn, are highly reactive and can react with free metal ions and/or metalloproteins, affecting cell metabolism. Therefore, the first chapter of the present study aims to investigate the reaction of cholesterol hydroperoxides (ChOOH) with cytochrome c (cytc), a heme protein involved in the mitochondrial electron transport. Spectroscopic analyses in the UV-Vis region showed that ChOOH induces a dose-dependent bleaching of cytc's Soret band. In addition, this reaction leads to the formation of carbon-centered radicals on both protein and lipid, suggesting a homolytic reduction of ChOOH. As consequences, cytc undergoes oligomerization, a process that can influence electron transport and apoptosis signaling. The reaction of cytc and ChOOH can produce, directly or indirectly, reactive species such as epoxides, aldehydes and ketones. Among them, cholesterol aldehydes, such as cholesterol secoaldehyde (CSec) and cholesterol carboxyaldehyde (ChAld), are of particular interest, since they were previously found elevated in atherosclerotic plaques and brain tissue of patients bearing neurodegenerative diseases. These species can also react with amino acid residues leading to protein denaturation and malfunction. With that in mind, the second chapter of this study aims to investigate the reaction of ChAld and cytc. Using mimetic membrane models and mass spectrometry analyses, we showed that ChAld covalently modifies cytc through a mechanism consistent with the formation of Schiff base adducts. Such modification occurs mostly at lysine residues that are known to interact with the membrane. The modifications have an influence in the affinity of cytc to the membrane, where they increase its binding to the membrane, a process that could affect the electron transport and apoptosis signaling. In the last and third chapter of this study we wanted an analytical tool that allowed the investigation of protein adduction promoted by cholesterol and other sterols-derived oxidation products. In a study performed in collaboration with the Porter group from Vanderbilt University, we used analyses based on click chemistry to search for protein adduction. To address that, we first synthesized derivatives of cholesterol and 7-dehydrocholesterol (7-DHC, the immediate precursor of cholesterol) containing an alkynyl group in the side chain. The alkynyl group can be ligated to an azide group through a cycloaddition reaction, in a process known as click chemistry. After the synthesis and characterization of alkynyl derivatives, Neuro2a cells were treated with alkynyl-7-DHC and alkynyl-cholesterol to check their metabolism. HPLC-MS/MS analyses showed that both alkynyl derivatives are metabolized and converted into their respective esters. In addition, using a cell model for Smith-Lemli-Optiz Syndrome (SLOS), a disease characterized by the deficiency in the dehydrocholesterol reductase 7, we showed that the characteristic accumulation of 7-DHC in SLOS patients might be associated with protein adduction promoted by its oxidation products, which might contribute to the development of the disease

A case of Smith-Lemli-Opitz syndrome confirmed by molecular analysis: Review of mutation spectrum of the DHCR7 gene in Korea

Smith-Lemli-Opitz syndrome (SLOS) is a rare autosomal recessive disorder caused by 7-dehydrocholesterol reductase deficiency. The characteristic clinical features are syndactyly of the second and third toes, facial dysmorphism, multiple malformations, and intellectual disability. Few cases of SLOS have been reported in Korea. We observed a male patient with SLOS who presented with typical facial features, undescended testes, microcephaly, bilateral syndactyly of the second and third toes, and cardiac defects, including patent ductus arteriosus and atrial septal defect. Mutation analysis of the DHCR7 gene identified compound heterozygous mutations of c.907G>A (p.Gly303Arg) and c.1055G>A (p.Arg352Gln). In a review of the literature, c.1054C>T (p.Arg352Trp) was the most common mutation reported in Far East Asian countries. This report describes the clinical features, biochemical data, molecular characteristics, and clinical outcome of a Korean patient with SLOS.

Rehabilitación oral de un paciente pediátrico con síndrome de Smith-Lemli-Opitz bajo anestesia general ambulatoria / Oral rehabilitation of a pediatric patient with smith-lemli-opitz syndrome under outpatient general anesthesia

El síndrome de Smith-Lemli-Opitz es una rara enfermedad hereditaria de transmisión autosómica recesiva. Se caracteriza por presenta hipocolesterolemia como consecuenciade una mutación del gen 7-deshidrocolesterol reductasa (7DHCR), lo que produce retrasomental, retardo en el crecimiento, microcefalia, micrognatismo y otras anomalías neurológicas sistémicas y físicas. Se presenta el caso de un paciente de tres años y nueve mesesafectado por este síndrome, quien acudió a la clínica de odontología pediátrica de la Facultad de Odontología de la Universidad Autónoma de Baja California, Tijuana, donde se inició historia médica y dental. Debido a su corta edad, la presencia de múltiples lesiones cariosas, conducta incontrolable, retraso mental y compromiso sistémico, se decidió realizar larehabilitación oral del paciente bajo anestesia general, la cual se describe detalladamente...

Smith-Lemli-Opitz syndrome is a rare autosomal recessive hereditary disease. It is caused by a mutation in the 7-dehydrocholesterol reductase (DHCR7) gene producing hypocholesterolemia,and consequence mental retardation, delayed growth, microcephaly, micrognathia and other systemic neurological and physical features. A case of a three-year-ninemonth-old patient affected by this syndrome who attended the Pediatric Dental Clinic of the Universidad Autónoma de Baja California Dental School at Tijuana is presented. Afterdoing medical and dental records and because of his young age, multiple dental cavities, uncontrollable behavior, mental retardation and medical status, oral rehabilitation under general anesthesia was performed. The anesthesia procedure is detailed...

A Novel DHCR7 Mutation in a Smith-Lemli-Opitz Syndrome Infant Presenting with Neonatal Cholestasis

Smith-Lemli-Opitz syndrome (SLOS) is an autosomal recessive malformation syndrome caused by a defect in cholesterol biosynthesis. The incidence is very low in Asians and only one case has been reported in Korea thus far. Recently, we found an infant with neonatal cholestasis. He had microcephaly, ambiguous genitalia, cleft palate, syndactyly of toes, patent ductus arteriosus and hypertrophic pyloric stenosis. The serum cholesterol was decreased and serum 7-dehydrocholesterol was markedly elevated. Genetic analysis of the DHCR7 gene identified a novel missense mutation (Pro227Ser) as well as a known mutation (Gly303Arg) previously identified in a Japanese patient with SLOS. Although rare in Korea, SLOS should be considered in the differential diagnosis of neonatal cholestasis, especially in patients with multiple congenital anomalies and low serum cholesterol levels.

A case of Smith-Lemli-Opitz syndrome diagnosed by identification of mutations in the 7-dehydrocholesterol reductase (DHCR7) gene / 소아과

Smith-Lemli-Opitz syndrome (SLOS) is a rare, autosomal recessive disease caused by an inborn error in cholesterol synthesis. Patients with this disease suffer from multiple malformations due to reduced activity of 7-dehydrocholesterol reductase (DHCR7), which increases 7-dehydrocholesterol (7DHC) and 8-dehydrocholesterol (8DHC) concentrations and decreases cholesterol concentration in body fluids and tissue. The SLOS phenotypic spectrum ranges from a mild disorder with behavioral and learning problems to a lethal disease characterized by multiple malformations. Here, we describe a newborn male with ambiguous genitalia who was diagnosed to have type II SLOS during the neonatal period. A clinical examination revealed low levels of unconjugated estriol in the maternal serum, and a variety of fetal ultrasound anomalies, including prenatal growth retardation. After birth, the infant was diagnosed to have congenital heart disease (Tetralogy of Fallot with severe pulmonary artery stenosis), cleft lip and palate, micrognathia, postaxial polydactyly, ambiguous genitalia, and cataracts. Clinical investigation revealed extremely low plasma cholesterol levels and the presence of mutation (homozygote of p.Arg352Gln) in the DHCR7 gene. The patient underwent palliative heart surgery (to widen the pulmonary artery) and received intravenous lipid supplementation. Cholesterol levels increased slightly, but not to normal values. The patient died from cardiopulmonary failure and sepsis 72 days after birth. This report provides the first description of a Korean patient with SLOS confirmed by verification of DHCR7 gene mutation and illustrates the need for early recognition and appropriate diagnosis of this disease.

Smith-Lemli-Opitz syndrome: clinical and biochemical findings in Brazilian patients

Smith-Lemli-Opitz syndrome (SLOS) or RSH syndrome comprises multiple congenital anomalies and mental retardation. The underlying defect is a deficiency in the activity of delta7-sterol reductase, which decreases cholesterol and increases 7-dehydrocholesterol (7-DHC) levels. Our aim was to identify and evaluate the frequency of SLOS manifestations in a group of Brazilian patients. Based on our own data and those reported previously, we present a simple method that allows the estimation of probabilities favoring the diagnosis of SLOS. We evaluated 30 patients clinically and determined their plasma levels of cholesterol and 7-dehydrocholesterol. In 11 patients, the diagnosis was confirmed by ultraviolet spectrophotometry (UV). Of 19 patients with normal laboratory results, 17 showed a high probability favoring the diagnosis of SLOS. The most significant signs and symptoms observed in over 2/3 of the biochemically confirmed cases were mental retardation (10/11), delayed neuropsychomotor development (10/11), syndactyly of 2nd/3rd toes (10/11), and craniofacial anomalies including microcephaly (11/11), incompletely rotated ears (8/11), palpebral ptosis (10/11), anteverted nostrils (10/11), and micrognathia (9/11). Genital anomalies were found in all male patients (6/6).

Síndrome de Optiz: avaliação neuropsicológica e fonoaudiológica / Opitz syndrome: neuropsychological assessment and speech

A Síndrome de Optiz G/BBB é uma condição pleiomórfica caracterizada por hipertelorismo, hiopospádia, associadas a inúmeras anomalias do Sistema Nervoso Central. É geneticamente heterogênea com parte dos casos apresentando herança ligada ao X e parte herança autossômica dominante. O objetivo deste estudo descritivo foi analisar os aspectos neuropsicológicos e fonoaudiológicos de um paciente diagnosticado com a Síndrome de Opitz, com¬parando os achados clínicos e instrumentais aos da literatura. O sujeito pesquisado foi R.A.C., 16 anos, sexo masculino e cursando a 4a. série do Ensino Fundamental. Os resultados obtidos evidenciaram desempenhos satisfatórios relacionados à memória remota, organização óptico-espacial do ato motor, assim como formas com¬plexas de praxias. Déficits maturacionais foram observados nas tarefas cognitivas relacionadas à organização percepto-motora das operações intelectuais no espaço, linguagem pragmática e semântica. As defasagens em áreas específicas da leitura, escrita e numérica, foram significativamente determinantes para o diagnóstico dos distúrbios da aprendizagem.

Optiz Syndrome, also named Hypertelorism-Hypospadias Syndrome, is determined by a dominant autosomic genetic condition linked to X chromosome. This syndrome causes anatomic and neurophysiological malformations and secondary impairments in different levels of development. The objective of this study was to analyze the speech audiologic and neuropsychological aspects of a patient carrier of Opitz Syndrome, comparing the clinical and instrumental findings to the ones in the literature known. The subject focused in the research was R.A.C., a 16 year-old male attending the fourth grade of primary school. The results obtained highlight satisfactory performances concerning remote memory, opticum-spatial organization of the motor act, as well as complex forms of praxias. Maturational deficits were observed in the cognitive tasks related to the motorial and perceptional organization of the intellectual operations in space, pragmatic language and semantics. Handicaps in specific areas of reading, writing and numeric were significantly determining for the diagnosis of learning disorders.

Optiz syndrome: audiological, speech and neuropsychological assessment

Optiz Syndrome, also named Hypertelorism-Hypospadias Syndrome, is determined by a dominant autosomic genetic condition linked to X chromosome. This syndrome causes anatomic and neurophysiological malformations and secondary impairments in different levels of development. The objective of this study was to analyze the speech, audiologic and neuropsychological aspects of a patient carrier of Opitz Syndrome, comparing the clinical and instru¬mental findings to the ones in the literature known. The subject focused in the research was R.A.C., a 16 year-old male attending the fourth grade of primary school. The results obtained highlight satisfactory performances concerning remote memory, opticum-spatial organization of the motor act, as well as complex forms of praxias. Maturational deficits were observed in the cognitive tasks related to the motorial and perceptional organization of the intellectual operations in space, pragmatic language and semantics. Handicaps in specific areas of reading, writing and numeric were significantly determining for the diagnosis of learning disorders.

Diagnosis of Smith-Lemli-Opitz syndrome by ultraviolet spectrophotometry

Smith-Lemli-Opitz syndrome (SLOS) is an autosomal recessive disorder due to an inborn error of cholesterol metabolism, characterized by congenital malformations, dysmorphism of multiple organs, mental retardation and delayed neuropsychomotor development resulting from cholesterol biosynthesis deficiency. A defect in 3ß-hydroxysteroid-delta7-reductase (delta7-sterol-reductase), responsible for the conversion of 7-dehydrocholesterol (7-DHC) to cholesterol, causes an increase in 7-DHC and frequently reduces plasma cholesterol levels. The clinical diagnosis of SLOS cannot always be conclusive because of the remarkable variability of clinical expression of the disorder. Thus, confirmation by the measurement of plasma 7-DHC levels is needed. In the present study, we used a simple, fast, and selective method based on ultraviolet spectrophotometry to measure 7-DHC in order to diagnose SLOS. 7-DHC was extracted serially from 200 æl plasma with ethanol and n-hexane and the absorbance at 234 and 282 nm was determined. The method was applied to negative control plasma samples from 23 normal individuals and from 6 cases of suspected SLOS. The method was adequate and reliable and 2 SLOS cases were diagnosed

Insuficiencia adrenal primária de causa genética / Primary adrenal insufficiency due to genetic causes

A insuficiência adrenal primária pode resultar em uma situaçäo de risco de vida, quando näo tratada ou quando o paciente é submetido a situações de estresse. Desta maneira, o reconhecimento, diagnóstico e tratamento correto e precoce da insuficiência adrenal é de fundamental importäncia na prática clínica, Por outro lado, o avanço no conhecimento dos mecanismos moleculares das diferentes causas genéticas de insuficiência adrenal tem permitido melhor entendimento näo só da fisiopatologia, mas também do desenvolvimento e fisiologia da glândula adrenal. Esta revisäo apresenta aspectos clínicos e moleculares de diferentes causas de insuficiência adrenal de origem genética.

Síndrome de Smith Lemli Opitz. Presentación de un caso con diagnóstico bioquímico / Syndrome of Smith-Lemli-Opitz. Presentation of a case with biochemical diagnosis

Se reporta un caso del Síndrome de Smith ­ Lemli ­ Opitz, en una niña de 4 años, con confirmación clínica y bioquímica (cromatografía de gases), por lo que sería el primer caso confirmado de esta patología en Cuba. Es una enfermedad autosómica dominante, y se produce por un déficit de la enzima 7 dehidrocolesterol reductasa, que cataliza el último paso del metabolismo del colesterol. Tiene una incidencia estimada de 1: 20 000 a 1: 60 000 nacimientos. Se realiza una revisión bibliográfica al respecto por lo poco conocida que es esta enfermedad

A Case of Trisomy 9 Mosaicism Mimicking Smith-Lemli-Opitz Syndrome

Trisomy 9 mosaicism is a disease characterized not only by intrauterine growth retardation and mental retardation but also congenital heart defects, musculoskeletal, genitourinary and CNS anomalies, as well as craniofacial anomalies such as microcephaly, micrognathia, narrowed temples, prominent occiput, broad-based nose with bulbous tip, low set ears, deeply set eyes, short palpebral fissure and small mouth. This syndrome was first reported back in 1973 by Haslam and others, and has hardly ever been reported since. In Korea, a complete form of trisomy 9 syndrome was first reported in 1998 by Chun and others, but trisomy 9 mosaicism has not been reported yet. We recently experienced a case with a patient who was most likely suspected as diet therapy requiring Smith-Lemli-Opitz Syndrome(SLO), since the patient had unilateral ptosis, hypospadias, micrognathia, simian crease, and low set ears, which are the characteristics not yet reported as trisomy 9 mosaicism, but most similar to Smith-Lemli-Opitz syndrome. Also, the patient did not show the typical characteristics of trisomy 9 mosaicism such as broad nose or enophthalmosis. However, further evaluation was taken in order to make the correct diagnosis, and the serum cholesterol level of the patient was shown to be normal, which implied normal cholesterol metabolism, but the chromosomal studies of the patient confirmed the karyotype of 47,XY,+9/46,XY, which proved that the patient has trisomy 9 mosaicism.

Síndrome de Opitz - relato de caso / Opitz syndrome - a case report

Descriçäo de quadro clínico de criança com síndrome de Opitz, estrabismo e outros distúrbios oculomotores. Relato de caso: Pacientes de três anos com hipospádia peno-escrotal, escroto bífido, ânus anteriorizado, micrognatia, pálato alto, fronte ampla, raiz nasal baixa, hipertelorismo e epicanto, implantaçäo baixa de orelhas, clinodactilia, espinha bífida e retardo do desenvolvimento neuromotor, interpretadas como manifestaçöes da síndrome de Opitz (OMIM *145410). Apresentava um ET alternante com fixaçäo cruzada (síndrome de Ciancia), associada a manifestaçöes da síndrome de Duane bilateral e desvio vertical (E/D), possivelmente devido a uma dissociaçäo motora entre o RSD e músculos palpebrais do OD. A criança faleceu após cirurgia de reconstruçäo anorretal. Discussäo: Apesar de comprometimentos oculares, näo há publicaçöes referentes á síndrome de Opitz em periódicos oftalmológicos. As com mençöes sobre estrabismo näo säo acompanhadas por relatos mais pormenorizados da motilidade ocular. O caso apresentava dissociaçöes oculomotoras importantes, mas seus esclarecimentos näo foram possíveis pelo falecimento prematuro da criança.

Sindrome de Smith-Lemli-Opitz / Smith-Lemli-Opitz Syndrome

Os autores relatam o caso de uma crianca com Sindrome de Smith-Lemli-Opitz, que era acompanhada por varias especialidades de forma especializada. A relevancia desse caso e destacar o atendimento do paciente como um todo...

Síndromes de Smith-Lemli-Optiz en dos hermanos. Presentación del caso / Smith-Lemli-Optiz Syndrome in two brothers. Case presentation

El síndrome de Smith-Lemli-Opitz es una entidad de etiología autosómica recesiva, que cursa con malformaciones congénitas, retraso del crecimiento y desarrollo pre y posnatal y es causa de muerte a temprana edad. No se conoce tratamiento, por lo que solamente se cuenta con el asesoramiento genético para evitar la aparición de nuevos casos.Se presenta el caso de dos hermanos, hijos de padres consanguíneos. Ambos fueron detectados desde el nacimiento y aun cuando se diagnosticaron al mes de vida, el asesoramiento genético proporcionando a los padres no fue efectivo, ya que después del primer hijo afectado tuvieron dos embarazos más, resultando afectado el producto del segundo de éstos. Se ha encontrado una deficiencia en la síntesis de colesterol, por lo que es posible hacer el diagnóstico prenatal en las mujeres que tienen antecedentes de gestas previas con esta enfermedad