Clinical characteristics and genetic analysis of a neonate with Smith-Magenis syndrome / 中华医学遗传学杂志

OBJECTIVE@#To explore the clinical features and genetic etiology for a neonate with Smith-Magenis syndrome (SMS).@*METHODS@#Copy number variation sequencing (CNV-seq) was applied to the neonate and his parents, and the genotype-phenotype correlation was analyzed.@*RESULTS@#On the second day after birth, the neonate had presented with pathological jaundice and immunodeficiency. Cranial MRI revealed ventricular enlargement and enlargement of cisterna magna. At 3 months, the infant has presented with square face, prominent forehead, deep-set eyes, hypertelorism, palpebral fissure upward and button noses. Genetic testing showed that he had carried a 2.9 Mb deletion in 17p11.2 region, seq[GRCh37] del(17)(p11.2)(chr17:16 836 379-19 880 992). The same deletion was not found in either parent.@*CONCLUSION@#SMS is mostly diagnosed in child and adulthood, but rarely in neonates. For neonates with SMS, the neurological and behavioral abnormalities have not been shown, but pathological jaundice, CNS abnormalities and immune deficiency may be the characteristics, which require attention of neonatal physicians.

Sleep disturbance associated with Smith-Magenis syndrome / 中华医学遗传学杂志

Smith-Magenis syndrome (SMS) (OMIM #182290) is a rare genetic disorder with a prevalence of 1 in 25 000 live births. Approximately 90% of SMS patients have harbored a 3.7 Mb interstitial 17p11.2 deletion involving the RAI1 gene, while 10% of cases have carried pathogenic variants of the RAI1 gene. SMS is characterized by sleep disturbance, intellectual impairment, developmental delay, craniofacial and cardiovascular anomalies, obesity, self injury, aggressive and autistic-like behaviors. Most SMS patients have sleep disorders such as short total sleep time, frequent night waking, short sleep onset, and early morning waking. The sleep disturbance may aggravate with age and persist throughout life. Three mechanisms have been delineated. The first concern was the abnormal secretion of melatonin, with high levels during daytime and low levels at night. Evaluation of the integrity of the intrinsically photosensitive retinal ganglion cell (ipRGC)/melanopsin system has found that SMS patients showed dysfunction in the sustained component of the pupillary light responses to blue light. Synchronization of daily melatonin profile and its photoinhibition are dependent on the activation of melanopsin. Dysfunction of the retina-melanin system may be one of the causes of melatonin spectrum disorders. Secondly, dysregulation of circadian rhythm gene expression has also been noted in mice and SMS patients. Finally, there may be association between sleep deprivation symptoms and DNA methylation patterns, which has provided new insights for SMS-associated sleep disorders and symptoms alike. Treatment for SMS-related sleep disorders is administered primarily through medications like melatonin tablets, which can alleviate insomnia-related sleep difficulties, in particular externalizing behavior in children. Researchers are also actively exploring other treatments for SMS currently.

Dental management for a child with smithmagenis syndrome under general anesthesia: case report

Introduction: Smith-Magenis Syndrome (SMS) is a genetic disease characterized by a neuro-behavioral deficiency caused by mutations or deletions at the 17p11.2 locus comprising the retinoic acid-induced 1 (RAI1) gene. The diagnosis is made through clinical analysis looking for characteristics and to prove this suspicion, a technique called Fluorescence In Situ Hybridization (FISH) is required. Objective: The aim of this case report is to be the first to describe the planning and execution of dental treatment for a 5yearold female patient with SMS under general anesthesia. Case report: The patient was admitted to the clinic of the Universidade Federal Fluminense, with possible dental pain, in the anamnesis the need for invasive treatment was observed in many dental elements and due to the patient's behavioral pattern, treatment under general anesthesia was chosen. Results: Procedures were performed (restorations and extractions) in the hospital in the same step. The child follow-up after the intervention every six month. Conclusion: SMS is a rare syndrome that requires extensive knowledge of the dentist and a detailed anamnesis to choose the best option to solve the case.

Introdução: A síndrome de Smith-Magenis (SMS) é uma doença genética caracterizada por uma deficiência neuro-comportamental causada por mutações ou deleções no locus 17p11.2 compreendendo o gene 1 induzido por ácido retinóico (RAI1). O diagnóstico é feito por meio de análises clínicas em busca de características e para comprovar essa suspeita, é necessária a técnica denominada Hibridização In Situ por Fluorescência (FISH). Objetivo: O objetivo deste relato de caso é o primeiro a descrever o planejamento e execução do tratamento odontológico para uma paciente do sexo feminino de 5 anos de idade com SMSsob anestesia geral. Relato do caso: O paciente deu entrada no ambulatório da Universidade Federal Fluminense, com possível dor dentária, na anamnese observou-se a necessidade de tratamento invasivo em diversos elementos dentais e devido ao padrão de comportamento do paciente optou-se pelo tratamentosob anestesia geral. Resultados: Os procedimentos foram realizados (restaurações e extrações) no hospital na mesma etapa. O acompanhamento da criança após a intervenção foi a cada seis meses. Conclusão: A SMS é uma síndrome rara que requer amplo conhecimento do dentista e uma anamnese detalhada para aescolha da melhor opção para a solução do caso.

El sueño del niño con trastornos del neurodesarrollo / The sleep in children with neurodevelopmental disorders

El sueño adecuado es necesario para el desarrollo sináptico y la maduración cerebral, un sueño de mala calidad tiene efectos perjudiciales en las funciones cognitivas, de atención, memoria y conducta de los niños. La preocupación sobre la alta prevalencia de los problemas del sueño es amplia en todo el mundo; las consecuencias de estos problemas son incluso más importantes en los niños portadores de trastornos del neurodesarrollo; estos niños a menudo tienen dificultades de inicio y mantenimiento del sueño y despertares nocturnos frecuentes que afectan a sus problemas de conducta. El propósito de este escrito es revisar el estado del arte de los problemas del sueño en los niños con trastornos del neurodesarrollo. En este punto, es importante tener en cuenta el ritmo circadiano, un reloj que genéticamente dirige los ritmos celulares de transcripción, traslación y metabolismos. Este reloj se combina con el ambiente diurno y nocturno coordinando estos mecanismos durante los ciclos luz/oscuridad, sueño/vigilia, frío/calor, ingesta/ayuno, tanto diariamente como en las diferentes estaciones. En conclusión, los problemas del sueño son un factor condicionante de la evolución y calidad de vida de los niños con trastornos del neurodesarrollo, que debe ser tenido en cuenta en todos los casos y ocupar un lugar preferente tanto en la etapa diagnóstica como en la terapéutica.

Adequate sleep is of critical need for a typical synaptic development and brain maturation, a poor quality sleep can have detrimental effects on children's' cognitive attention, memory, mood regulation, and behavior functions. Great concern has been voiced out regarding the high prevalence of poor sleep in children worldwide, the effects of poor sleep may be even more pronounced in children with neurodevelopmental disorders; these children often have difficulties with falling and staying asleep and with night awakenings, this has a strong association with daytime behavior problems. The purpose of this article is to provide an overview of the state of the science of sleep in children with a neurodevelopmental disorder. In this context, it is important to take the circadian cycle into account, a genetically encoded clock that drives cellular rhythms of transcription, translation and metabolism. The circadian clock interacts with the diurnal and nocturnal environment that also drives transcription and metabolism during light/dark, sleep/wake, hot/cold and feast/fast daily and seasonal cycles In conclusion, the sleep problems are a conditioning factor in the evolution and quality of life of children with neurodevelopmental disorders that must be taken into account in all cases and occupy a preferential place in both the diagnostic and the therapeutic stages.

Genetic diagnosis of a child with Smith-Magenis syndrome / 中华医学遗传学杂志

OBJECTIVE@#To explore the molecular mechanism of a girl with developmental delay and intellectual disability.@*METHODS@#Chromosomal karotypes of the child and her parents were analyzed with routine G-banding method. Their genomic DNA was also analyzed with array comparative genomic hybridization (aCGH) for chromosomal duplications/deletions.@*RESULTS@#No karyotypic abnormality was detected in the child and her parents, while aCGH has identified a de novo 3.37 Mb deletion at 17p11.2 in the child.@*CONCLUSION@#The child was diagnosed with Smith-Magenis syndrome, for which RAI1 may be the causative gene.

Diagnosis of Smith-Magenis Syndrome in a Patient with Mental Retardation and Sleep Disturbance Confirmed by Multiplex Ligation-dependent Probe Amplification

No abstract available.

A Case of Smith-Magenis Syndrome with Multiple Organ Malformations

Smith-Magenis syndrome (SMS) is a genetic disease caused by microdeletion of p11.2 in chromosome 17. SMS patients have characteristic facial features and accompanying congenital malformations involving the brain, cardiovascular system, and urinary tract. Compared with the distinctive facial characteristics, organ malformations are less common. Several cases of SMS with tetralogy of Fallot have been reported in Korea, none of which were accompanied by other organ malformations. We present the first case report in Korea of an SMS patient with malformations of the brain, heart, and urinary tract.

Phenotypic and genetic analysis of a child carrying a 17q11.2 microdeletion / 中华医学遗传学杂志

<p><b>OBJECTIVE</b>To analyze a child with facial abnormalities with combined cytogenetic and molecular techniques and delineate its clinical phenotype.</p><p><b>METHODS</b>Neuropsychological profile of the child was analyzed. Color Doppler, CT and MRI were used for detecting the nodules in the body. Conventional peripheral blood karyotypes of the child and his parents were analyzed with G-banding. Array-comparative genomic hybridization (aCGH) was performed to detect minor structural chromosomal abnormalities.</p><p><b>RESULTS</b>The child had mental retardation, maxillofacial dysmorphism on the right side, and irregular solid nodules on the back. The karyotypes of the child and his parents were all normal, while aCGH has identified a de novo constitutive 1.2 Mb deletion at 17q11.2 in the child. The aCGH results of his parents were normal.</p><p><b>CONCLUSION</b>The de novo 17q11.2 microdeletion probably underlies the facial abnormalities and neurofibromatosis in the patient.</p>

Reciprocal Deletion and Duplication of 17p11.2-11.2: Korean Patients with Smith-Magenis Syndrome and Potocki-Lupski Syndrome

Deletion and duplication of the -3.7-Mb region in 17p11.2 result in two reciprocal syndrome, Smith-Magenis syndrome and Potocki-Lupski syndrome. Smith-Magenis syndrome is a well-known developmental disorder. Potocki-Lupski syndrome has recently been recognized as a microduplication syndrome that is a reciprocal disease of Smith-Magenis syndrome. In this paper, we report on the clinical and cytogenetic features of two Korean patients with Smith-Magenis syndrome and Potocki-Lupski syndrome. Patient 1 (Smith-Magenis syndrome) was a 2.9-yr-old boy who showed mild dysmorphic features, aggressive behavioral problems, and developmental delay. Patient 2 (Potocki-Lupski syndrome), a 17-yr-old boy, had only intellectual disabilities and language developmental delay. We used array comparative genomic hybridization (array CGH) and found a 2.6 Mb-sized deletion and a reciprocal 2.1 Mb-sized duplication involving the 17p11.2. These regions overlapped in a 2.1 Mb size containing 11 common genes, including RAI1 and SREBF.

Clinical and genetic study of a case with Smith-Magenis syndrome / 中华儿科杂志

<p><b>OBJECTIVE</b>To explore the clinical feature and genetic diagnosis for Smith-Magenis syndrome (SMS).</p><p><b>METHOD</b>The clinical data, including craniofacial anomalies, physical and mental status were analyzed. Routine and high resolution G-banding was performed to analyze the karyotype of the patient and her parents, and array comparative genomic hybridization (array CGH) was used to detect small chromosome anomaly.</p><p><b>RESULT</b>A-two-year old girl was sent to our clinic for mental retardation and cardiac malformation. Some sleep problems were reported by parents, including difficulties falling asleep, shortened sleep cycles. She also had some neurobehavioral symptoms including hyperactivity and self-injurious behaviors head-banging. She had distinctive craniofacial features including low hairline, frontal bossing, a broad face, broad nasal bridge, a tented upper lip, prognathism, low-set ears and high-vaulted arch. She had moderate mental retardation. Cardiac findings included ventricular septal defect, atrial septal defect, overriding aorta and pulmonary hypertension. Primary ventriculomegaly was seen in magnetic resonance imaging (MRI). Routine karyotype analysis showed a karyotype of 46, XX. However, high resolution karyotype analysis showed a suspected partial deletion of the short arm of chromosome 17. Array comparative genomic hybridization (array CGH) finely mapped the deletion to a 3.8 Mb region on 17p11.2. The molecular karyotype was then ascertained as 46, XX.arr17p11.2(16543655-20374751)×1dn. The parents had normal karyotypes.</p><p><b>CONCLUSION</b>Smith-Magenis syndrome is a multisystem disorder characterized by developmental delay and mental retardation, distinctive craniofacial features, sleep disturbance and behavioral problems. Array comparative genomic hybridization (array CGH) finely mapped the deletion on 17p11.2.</p>

Two cases of Smith-Magenis syndrome / 소아과

SmithMagenis syndrome (SMS) is a rare disorder with multiple congenital anomalies caused by a heterozygous interstitial deletion involving chromosome 17p11.2, where the retinoic acid-induced 1 (RAI1) gene is located, or by a mutation of RAI1. Approximately 90% of the patients with SMS have a detectable 17p11.2 microdeletion on fluorescence in-situ hybridization (FISH). SMS is characterized by mental retardation, distinctive behavioral features, craniofacial and skeletal anomalies, speech and developmental delay, and sleep disturbances. Although there are some intervention strategies that help individuals with SMS, there are no reported specific interventions for improving the outcome in children with SMS. Here, we report two cases of SmithMagenis syndrome.

Two Cases of Smith-Magenis Syndrome with Tetralogy of Fallot Confirmed by FISH / 대한진단검사의학회지

Smith-Magenis syndrome (SMS) is characterized by distinctive facial features, developmental delay, cognitive impairment, and behavioral abnormalities and associated with interstitial deletion of chromosome 17p11.2. We report 2 cases of SMS with tetralogy of Fallot. The first patient was reported having a normal conventional karyotype 7 years ago. However, as she grew up, she showed more compatible findings with SMS in behavior and phenotype. On the second cytogenetic study, interstitial deletion of 17p11.2 was detected by conventional banding technique which had 550 band resolution and it was confirmed by metaphase fluorescence in situ hybridization (FISH) using D17S258 SMS probe (Oncor, Gaithersburg, MD, USA). The second patient showed subtle phenotypic feature except microcephaly and cardiac anomalies was confirmed as SMS by cytogenetic analysis and FISH. We suggest that FISH should be performed not to overlook the submicroscopic deletion when SMS is clinically suspected, even though cytogenetist can not detect any anomalies on the conventional cytogenetics. A confirmatory diagnosis using FISH would be helpful in terms of guiding medical management and leading to proper genetic counseling.