1.Sleep disturbance associated with Smith-Magenis syndrome.
Chinese Journal of Medical Genetics 2021;38(12):1262-1265
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.
Animals
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Circadian Rhythm
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Humans
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Melatonin
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Mice
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Sleep
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Sleep Wake Disorders/genetics*
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Smith-Magenis Syndrome/genetics*
2.Genetic diagnosis of a child with Smith-Magenis syndrome.
Yue GAO ; Dong WU ; Xiaodong HUO ; Mengting ZHANG ; Qiaofang HOU ; Hongdan WANG ; Shixiu LIAO
Chinese Journal of Medical Genetics 2019;36(7):724-726
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.
Child
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Chromosome Deletion
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Chromosome Duplication
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Chromosomes, Human, Pair 17
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genetics
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Comparative Genomic Hybridization
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Female
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Humans
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Karyotyping
;
Smith-Magenis Syndrome
;
genetics
3.Clinical and genetic study of a case with Smith-Magenis syndrome.
Li-xiao SHEN ; Jin-song ZHANG ; Xing JI ; Ya XING ; Juan HU ; Jiong TAO ; Bing XIAO
Chinese Journal of Pediatrics 2012;50(3):227-230
OBJECTIVETo explore the clinical feature and genetic diagnosis for Smith-Magenis syndrome (SMS).
METHODThe 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.
RESULTA-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.
CONCLUSIONSmith-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.
Child, Preschool ; Chromosome Deletion ; Chromosomes, Human, Pair 17 ; Female ; Humans ; Intellectual Disability ; Karyotyping ; Smith-Magenis Syndrome ; diagnosis ; genetics
4.Phenotypic and genetic analysis of a child carrying a 17q11.2 microdeletion.
Hongdan WANG ; Zhanqi FENG ; Ke YANG ; Yue GAO ; Xiaodong HUO ; Litao QIN ; Guiyu LOU
Chinese Journal of Medical Genetics 2017;34(5):695-698
OBJECTIVETo analyze a child with facial abnormalities with combined cytogenetic and molecular techniques and delineate its clinical phenotype.
METHODSNeuropsychological 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.
RESULTSThe 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.
CONCLUSIONThe de novo 17q11.2 microdeletion probably underlies the facial abnormalities and neurofibromatosis in the patient.
Child, Preschool ; Chromosome Banding ; Chromosome Deletion ; Chromosomes, Human, Pair 17 ; genetics ; Comparative Genomic Hybridization ; Humans ; Intellectual Disability ; genetics ; Karyotyping ; Male ; Maxillofacial Abnormalities ; genetics ; Phenotype ; Smith-Magenis Syndrome ; genetics
5.Genetic diagnosis of a case of Smith-Magenis syndrome due to a rare small-scale deletion.
Baodong TIAN ; Donglan YU ; Guangli WANG ; Bingyi HUANG ; Chunjiang ZHU
Chinese Journal of Medical Genetics 2022;39(9):1005-1010
OBJECTIVE:
To report on a case of Smith-Magenis syndrome (SMS) due to a rare small-scale deletion.
METHODS:
Muscle samples from the the third fetus was collected after the in Medical history and clinical data of the patient were collected. The child and his parents were subjected to chromosome karyotyping analysis, multiplex ligation-dependent probe amplification (MLPA) and copy number variation sequencing (CNV-seq).
RESULTS:
The child was found to have a normal karyotype. MLPA and CNV-seq detection showed that he has harbored a 1.22 Mb deletion and a 0.3 Mb duplication in the 17p11.2 region. Neither of his parents was found to have similar deletion or duplication.
CONCLUSION
The child was diagnosed with SMS due to a rare 1.22 Mb deletion in the 17p11.2 region, which is among the smallest deletions associated with this syndrome.
Abnormalities, Multiple/genetics*
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Child
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Chromosome Deletion
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Chromosomes, Human, Pair 17
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DNA Copy Number Variations
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Humans
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Intellectual Disability/genetics*
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Male
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Smith-Magenis Syndrome/genetics*
6.Clinical characteristics and genetic analysis of a neonate with Smith-Magenis syndrome.
Heng SHU ; Tongsheng YE ; Guanghui LIU ; Liying DAI ; Ping ZHA ; Xianhong LI ; Yuwei ZHAO ; Xiaoshan ZHU ; Hong ZHENG
Chinese Journal of Medical Genetics 2022;39(4):409-412
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.
Adult
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Chromosome Deletion
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Chromosomes, Human, Pair 17
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DNA Copy Number Variations
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Genetic Testing
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Humans
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Infant, Newborn
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Intellectual Disability/genetics*
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Male
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Phenotype
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Smith-Magenis Syndrome/genetics*
7.Reciprocal Deletion and Duplication of 17p11.2-11.2: Korean Patients with Smith-Magenis Syndrome and Potocki-Lupski Syndrome.
Cha Gon LEE ; Sang Jin PARK ; Jun No YUN ; Shin Young YIM ; Young Bae SOHN
Journal of Korean Medical Science 2012;27(12):1586-1590
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.
Adolescent
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Asian Continental Ancestry Group/*genetics
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Child, Preschool
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*Chromosomes, Human, Pair 17
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Comparative Genomic Hybridization
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Developmental Disabilities/etiology/genetics
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Gene Deletion
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Gene Duplication
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Humans
;
Intellectual Disability/etiology/genetics
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Karyotyping
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Male
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Smith-Magenis Syndrome/diagnosis/*genetics
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Sterol Regulatory Element Binding Protein 1/genetics
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Transcription Factors/genetics