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Representation of the 17p11.2 deletion. A. Ideogram of chromosome 17; the arrow shows the deleted region. B. Partial karyotype in GTG banding (300 bands) showing the del(17p11.2). C-D. Metaphase FISH with the specific probe for the critical region of Smith-Magenis syndrome, region control gene LIS (red, C and D), target probe gene FLII (green, C) and target probe gene RAI1 (green, D).
Source publication
Smith-Magenis syndrome (SMS) is a complex congenital anomaly characterized by craniofacial anomalies, neurological and behavioral disorders. SMS is caused by a deletion in region 17p11.2, which includes the RAI1 gene (90% of cases), or by point mutation in the RAI1 gene (10% of cases). Laboratory diagnosis is through cytogenetic analysis by GTG ban...
Context in source publication
Context 1
... clinical data of our seven SMS patients were similar to those of published studies except some clinical signs that were shown to be statistically significant, such as dental anomalies, strabismus, ear infec- tions, deep hoarse voice, hearing loss, and cardiac defects (Table 1 and Figure 1). The GTG chromosome banding and high-resolution GTG chromosome banding showed seven cases with deletion 17p11. 2 The FISH analysis confirmed the GTG chromosome banding results (Figure 2). Table1. ...
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Background & objectives:
Developmental delay (DD)/mental retardation also described as intellectual disability (ID), is seen in 1-3 per cent of general population. Diagnosis continues to be a challenge at clinical level. With the advancement of new molecular cytogenetic techniques such as cytogenetic microarray (CMA), multiplex ligation-dependent p...
Citations
... Early SMS research identified conductive and sensorineural hearing loss in 66% of cases (six of nine individuals in this initial study; Smith et al., 1986). Later studies of hearing in SMS reported the prevalence of hearing loss ranging from as low as 48% of cases (Greenberg et al., 1996) to as high as 62%-68% (Edelman et al., 2007;Gamba et al., 2011;Potocki et al., 2003). Conductive hearing loss for younger children with SMS appeared to be related to otitis media (Brendal et al., 2017;Greenberg et al., 1996). ...
... The current study found that 35% of subjects had a reported hearing loss. This is lower than previous reported hearing loss in approximately 48%-72% of SMS cases (e.g., Brendal et al., 2017;Edelman et al., 2007;Gamba et al., 2011;Potocki et al., 2003;Smith et al., 1986). The difference between the current results and previous findings may be due to the nature of data collection. ...
... If pure-tone audiometry had been performed here to identify the presence and type of hearing loss, the prevalence may have been higher. While the current study included a large cohort of subjects with SMS compared to many previous studies (e.g., Edelman et al., 2007;Gamba et al., 2011;Potocki et al., 2003), Brendal et al. (2017) directed tested 133 subjects with SMS and obtained pure-tone thresholds (250-8000 Hz). As a result, the results reported by Brendal et al. (2017) are more likely to be a better estimate of hearing loss prevalence in those with SMS than what was found here; however, we would argue that any prevalence related to conductive hearing loss should be interpreted with caution since it can be intermittent when it occurs as a result of otitis media and, as a consequence, may vary from study to study. ...
Purpose
Smith–Magenis syndrome (SMS), a rare, genetically linked complex developmental disorder caused by a deletion or mutation within chromosome 17p11.2, is associated with delays in speech-language development, otopathology, and hearing loss, yet previous studies lack comprehensive descriptions of hearing and communication profiles. Here, analyses of patient registry data expand what is known about speech, language, hearing, and otopathology in SMS.
Method
International speech-language and hearing registry survey data for 82 individuals with SMS were analyzed using descriptive and inferential statistics. Hearing loss, history of otitis media and pressure equalization (PE) tubes, communication mode, expressive/receptive language, and vocal quality were analyzed for all subjects and subjects grouped by age. Statistical methods included descriptive statistics and Pearson's chi-square tests of independence to test for differences between age groups for each variable of interest. Association analyses included Pearson's correlations.
Results
Hearing and otological analyses revealed that 35% of subjects had hearing loss, 66% had a history of otitis media, and 62% had received PE tubes. Speech-language analyses revealed that 60% of subjects communicated using speech, 79% began speaking words at/after 24 months of age, 92% combined words at/after 36 months, and 41% used sign language before speech. There was a significant association between the age that first words were spoken and the age that PE tubes were first placed. Communication strengths noted in more than 40% of subjects included social interest, humor, and memory for people, past events, and/or facts.
Conclusions
Significant delays and impairment in speech-language were common, but the majority of those with SMS communicated using speech by age 6 years. Age was a significant factor for some aspects of hearing loss and communication. Neither hearing loss nor otitis media exacerbated language impairment. These results confirm and extend previous findings about the nature of speech, language, hearing, and otopathology in those with SMS.
... The phenotype associated with SMS is characterized by a set of features that includes a variable intellectual deficit, craniofacial and skeletal anomalies, self-injurious and attention-seeking behaviors, speech and motor delay, and an auditory phenotype characterized by hyperacusis and conductive hearing loss (Brendal et al., 2017;Elsea & Girirajan, 2008;Gamba et al., 2011;Smith et al., 2010). To this phenotype it is also associated a high incidence of sleep disorders (Angriman, Caravele, Novelli, Ferri, & Bruni, 2015;Shayota & Elsea, 2019;Trickett, Heald, Oliver, & Richards, 2018). ...
Smith–Magenis syndrome (SMS) is a rare neurodevelopmental disorder with mild-to-moderate intellectual disability. Speech and language impairments have not been well described as part of the SMS phenotype. This study reports the speech and language characteristics presented by a classical SMS case, a 20-year-old woman with positive deletion in the region 17p11.2. The case presented a borderline IQ on verbal and performance Wechsler scales. Language standardized tests (i.e., Peabody, Token test, CEG test and Boehm test) and naturalistic language sample (i.e. conversation and story generation) were used to assess speech and language performance. Speech characteristics included imprecise speech, with a high speech rate, hoarse voice, hypernasality and intelligibility deficits. The performance in all standardized tests was poor. Socio-communicative deficits included repetitive and persistent verbal behavior, difficulties in the use of linguistic strategies to repair communication breakdowns, limited vocabulary production and short overall length utterances with reduced grammatical components. The results contribute to expanding knowledge about the SMS phenotype, also to highlight the need to include speech and language evaluation as part of the clinical assessment of SMS and, at the same time, to draw attention to the need to include early communications skills in language intervention programs.
... In the original delineation of SMS, both conductive and sensorineural hearing losses were noted in six of nine cases although audiometric data were not included (Smith et al., 1986). Subsequent clinical series (Girirajan et al., 2006;Greenberg et al., 1991;Potocki, Shaw, Stankiewicz, & Lupski, 2003) and meta-analyses (Edelman et al., 2007;Gamba et al., 2011) describing the overall clinical phenotype of persons with SMS list hearing loss as a frequent manifestation, occurring in approximately two thirds of reported cases. The loss has been historically considered mild in most cases (Greenberg et al., 1996) and attributed to a high prevalence of chronic and recurrent otitis media associated with SMS (Elsea & Girirajan, 2008;Smith, Dykens, & Greenberg, 1998b). ...
... Our data show that hearing loss is a frequent manifestation of the SMS phenotype. On the basis of the representative audiogram, hearing loss affects up to 78.9% of individuals in at least one ear and occurs at a slightly higher rate than the previously reported prevalence of 62%-68% (Edelman et al., 2007;Gamba et al., 2011;Girirajan et al., 2006;Greenberg et al., 1991Greenberg et al., , 1996Potocki et al., 2003). In addition, when we reviewed all audiograms of our 76 participants, 90.7% had hearing loss on at least one assessment. ...
... It is possible that our cutoff of 15 dB HL for normal hearing is more stringent than that used in other studies, accounting for the higher prevalence of hearing loss in our cohort. Similar to previous observations, hearing loss of a mild or lesser degree occurred most often; however, thorough comparison is not possible because degree of hearing loss is not operationally defined or adequately addressed in previous reports of hearing status in persons with SMS (Edelman et al., 2007;Gamba et al., 2011;Girirajan et al., 2006;Greenberg et al., 1991Greenberg et al., , 1996Potocki et al., 2003). ...
Purpose
The purpose of this study was to describe the auditory phenotype of a large cohort with Smith–Magenis syndrome (SMS), a rare disorder including physical anomalies, cognitive deficits, sleep disturbances, and a distinct behavioral phenotype.
Method
Hearing-related data were collected for 133 individuals with SMS aged 1–49 years. Audiogram data (97 participants) were used for cross-sectional and longitudinal analyses. Caregivers completed a sound sensitivity survey for 98 individuals with SMS and a control group of 24 unaffected siblings.
Results
Nearly 80% of participants with interpretable audiograms (n = 76) had hearing loss, which was typically slight to mild in degree. When hearing loss type could be determined (40 participants), sensorineural hearing loss (48.1%) occurred most often in participants aged 11–49 years. Conductive hearing loss (35.2%) was typically observed in children aged 1–10 years. A pattern of fluctuating and progressive hearing decline was documented. Hyperacusis was reported in 73.5% of participants with SMS compared with 12.5% of unaffected siblings.
Conclusions
This study offers the most comprehensive characterization of the auditory phenotype of SMS to date. The auditory profile in SMS is multifaceted and can include a previously unreported manifestation of hyperacusis. Routine audiologic surveillance is recommended as part of standard clinical care.
... S mith-Magenis syndrome (SMS, OMIM 182290) is a complex genetic multisystem disorder characterized by a variable pattern of cognitive deficits accompanied by a distinctive behavioral phenotype that includes a range of challenging behaviors, including self-injury, aggression, impulsivity, attention seeking, and sleep disturbance in addition to developmental delay. 1,2 SMS is still not well-known because it is an extremely rare misdiagnosed disorder characterized by subtle facial dysmorphology that progresses with age and include brachycephaly, mid-facial hypoplasia with broad flat midface, broad nasal bridge, prognathism, and clinical features that overlap with other developmental delay such as infantile hypotonia, short stature, and intellectual disability syndromes as 1p36 deletion syndrome, 9q34 deletion syndrome (Kleefstra syndrome), 22q11.2 deletion syndrome (DiGeorge syndrome or Velocardiofacial syndrome), Fragile x syndrome, brachydactyly-intellectual deficit syndrome (del 2q37), Down syndrome, Prader-Willi syndrome, Sotos syndrome, and Williams syndrome. ...
... Functional assays have identified collection of genes that are either upregulated or downregulated as a consequence of RAI1 haploinsufficiency. 1,2 One of the cardinal signs of SMS is severe sleep disturbances and maladaptative daytime behavior (ie frequent nighttime awakenings, sleepiness in day/frequent napping, early morning awake times). These features have been linked to an abnormal circadian secretion pattern of melatonin. ...
Smith–Magenis syndrome (SMS0) is a complex and rare genetic multisystem disorder characterized by a variable pattern of cognitive deficits accompanied by a1 distinctive behavioral phenotype. SMS is characterized by subtle facial dysmorphology, short stature, sleep disturbances, and neurobehavioral abnormalities. Little is known about the manifestation of his unique case among Arab population and its strategic treatment.
This study comes to present a case of SMS in an Arab newborn male who was born in spontaneous delivery on June 29, 2015, with tachypnea, tracheomalacia, and mild hypotonia. The newborn was admitted on the Neonatal Intensive Care Unit (NICU), and various laboratory examinations and clinical examinations were performed.
Throughout his hospitalization, feeding difficulties appeared and thus a peripheral venous catheter was inserted in the left leg.
After 22 days of follow-up and hospitalizations, the patient status improved and he was discharged with recommendations to be in follow up in pediatric outpatient clinic.
However, notwithstanding the different investigations, intermittent tachypnea continued at a rate of 72 to 77 breaths/min. Search for diagnosis begin intensively owing to persistence of tachypnia, mild hypotonia, feeding difficulties, sleep disturbances, and mild dysmorphic facial features. Suspicions of genetic abnormalities were considered and blood samples were sent for chromosome analysis and for fluorescent in situ hybridization (FISH) testing.
The genetic results revealed the following: cytogenetic findings: 46, XY, del(17)(p11.2) and the FISH results: del(17)(p11.2p11.2) (D17S29). The chromosome diagnosis revealed an interstitial deletion of 17p11.2 and the diagnosis of the SMS was confirmed.
Accurate clinical diagnosis, therapeutic assessments and a holistic management plans, including multidiscipline therapeutic strategies, periodic neuro-developmental assessments, and an early intervention programs, are recommended.
However, cytogenetic analysis or FISH using an RAI1-specific probe is the most frequently used technique for DS. Sleep and behavioral disturbances treatment include a combination of the daytime dose of acebutolol with an evening oral dose of melatonin. Melatonin as chronobiotic, antioxidant, and analgesic agent showed to be effective in different primary sleep disorders and in those associated with neurobehavioral disorders. Based on the beneficial effect of melatonin, it will be useful to use serum levels of melatonin as a follow-up test.
... Rate of Smith-Magenis syndrome (SMS) is from 1 in 15000 to 1 in 25000 births (GAMBA et al., 2011). Smith-Magenis syndrome detection age varies from 6 months to 6 years (MONCLA et al., 1991;GUPTA et al., 2015) sometimes later (BLANCO-BARCA et al., 2003;TSIRIKOS et al., 2010;GAMBA et al., 2011). ...
... Rate of Smith-Magenis syndrome (SMS) is from 1 in 15000 to 1 in 25000 births (GAMBA et al., 2011). Smith-Magenis syndrome detection age varies from 6 months to 6 years (MONCLA et al., 1991;GUPTA et al., 2015) sometimes later (BLANCO-BARCA et al., 2003;TSIRIKOS et al., 2010;GAMBA et al., 2011). By MONCLA et al. (1991) the symptoms of Smith-Magenis syndromes were described as mental retardation, behavioural problems, developmental delay (speech delay), facial dysmorphism, brachycephaly, a broad face with a flat midface, short and broad hands, hypotonia, hearing loss, subnormal EEG with slow rhythms. ...
... Also some patients had cardiac and renal malformations, cystic encephalomalacia, developmental delay and sleep disturbances (GUPTA et al., 2015). Minor craniofacial anomalies, self-injurious behavior, auto-amplexation (self-hugging), signs of peripheral neuropathy, dental anomalies, strabismus, deep hoarse voice, congenital heart disease and seizures also are added to clinical phenotype of syndrome (SCHLESINGER et al., 2003;GAMBA et al., 2011). Our Smith-Magenis patients (Patient 4 and Patient 5) had cranium defect, facial dysmorphism, flat face, thicker hands, heart defects, small cysts in brain and global development delay. ...
Microdeletion syndrome is a rare condition which can be diagnosed by
fluorescent in situ hybridization (FISH) method. We analyzed microdeletion
syndromes cases during ten years period (2005-2015) at The Hospital of
Lithuanian University of Health Sciences. We report 2 patients with
Prader-Willi syndrome, 2 patients with Smith-Magenis syndrome, 1 patient
with Angelman syndrome and 1 patient with Cri du Chat syndrome. All
syndromes were confirmed by FISH. These cases contain mainly data about
phenotype abnormalities and clinical symptoms.
... Certain patients show mild to moderate mental retardation, while others exhibit atypical facial features, and cardiac, renal and otolaryngologic abnormalities (1)(2)(3). However, the correlation between genotype and phenotype is not well understood in SMS (3)(4)(5). ...
Smith‑Magenis syndrome (SMS) is a rare condition with multiple congenital malformations caused by the haploinsufficiency of RAI1 (deletion or mutation of RAI1). However, the correlation between genotype and phenotype is not well understood. The present study describes the prenatal diagnosis of monozygotic twins with a 17p11.2 deletion, which is indicative of SMS, who presented with discordant phenotypes and uteroplacental insufficiency. A high‑resolution genome‑wide single nucleotide polymorphism array revealed a 3.7‑Mb deletion in the 17p11.2 chromosome region. Accurate breakpoints of the deletion in these patients were used to identify correlations between SMS and the concomitant phenotypes, particularly uteroplacental insufficiency, which has rarely been investigated in SMS. In addition, no exonic mutations were identified in or affected known disease‑associated loci that could explain the congenital anomalies, according to a model that accounts for the possibility of incomplete penetrance. Furthermore, a novel benign copy number variation (a duplication of 195 kb at 13q12.13) was identified but was unlikely to be clinically significant in the discordant phenotypes of the twins. The present study showed that multiple interacting genetic and environmental factors are involved in determining the variance of the SMS phenotype.
... ている(e.g., Clarke & Boer, 1998;Dykens, 2004 & Smith, 1999;Edelman et al., 2007;Gamba et al., 2011;Greenberg et al., 1996;Hindenbrand & Smith, 2012) の結果を 7 項目に分類し，それぞれの発症率について， 各文献に載せられていた対象者数と該当者数に基づき再 計算を行った( , 1997;Dykens & Smith., 1998;Finucane et al., 2001;Greenberg et al., 1996;Madduri, Voigt, Llorente, Lupski, & Potocki, 2006;Martin et al., 2006;Osorio et al., 2012;Sloneem et al., 2011;Udwin et al., 2001;Wilde et al., 2013) 。知能やコミュニケーション能力の特徴について は先行研究の結果を WISC-Ⅲ (Wechsler, 1992) ・全検査 IQ：48.5(42～60；n＝22) ・言語性 IQ：53.9(47～64；n＝20)動作性 ...
... 先行研究で示された SMS のある人にみられる行動問題の発現率と他の症候群等との比較結果 注．Arron et al., 2011;Clarke & Boer, 1998;Dykens & Smith, 1998; Edelman et al., 2007;Gamba et al., 2011; Greenberg et al., 1996; Langthorn & McGill, 2012;Sarimski, 2004;Sloneem et al., 2011 を参考に筆者らが作成した。 † 印は Dykens & Smith, 1998 ...
... 45 In contrast, FISH allows for precise gene copy number determination in individual cells, rendering it independent from the purity of cancer tissues or presence of aneusomy. [46][47][48] 8p deletions were unevenly distributed between breast cancer subtypes, providing further support for the existence of biological differences between different subtypes of breast cancer. The higher rate of 8p deletions in NST as compared to lobular cancer is not surprising as most genomic alterations are more frequent in NST than in lobular carcinomas such as amplifications of HER2, 41,49 MYC, 41 MDM1, 41 and AIB1, 50 or overexpression of p53. ...
Deletions of chromosome 8p occur frequently in breast cancers, but analyses of its clinical relevance have been limited to small patient cohorts and provided controversial results. A tissue microarray with 2,197 breast cancers was thus analyzed by fluorescence in-situ hybridization using an 8p21 probe in combination with a centromere 8 reference probe. 8p deletions were found in 50% of carcinomas with no special type, 67% of papillary, 28% of tubular, 37% of lobular cancers and 56% of cancers with medullary features. Deletions were always heterozygous. 8p deletion was significantly linked to advanced tumor stage (p<0.0001), high-grade (p<0.0001), high tumor cell proliferation (Ki67 Labeling Index; p<0.0001), and shortened overall survival (p<0.0001). For example, 8p deletion was seen in 32% of 290 grade 1, 43% of 438 grade 2, and 65% of 427 grade 3 cancers. In addition, 8p deletions were strongly linked to amplification of MYC (p<0.0001), HER2 (p<0.0001), and CCND1 (p=0.001), but inversely associated with ER receptor expression (p=0.0001). Remarkably, 46.5% of 8p-deleted cancers harbored amplification of at least one of the analyzed genes as compared to 27.5% amplifications in 8p-non-deleted cancers (p<0.0001). In conclusion, 8p deletion characterizes a subset of particularly aggressive breast cancers. As 8p deletions are easy to analyze, this feature appears to be highly suited for future DNA based prognostic breast cancer panels. The strong link of 8p deletion with various gene amplifications raises the possibility of a role for regulating genomic stability.
... The prevalence of SMS worldwide was estimated to be at 1:15,000 to 1:25,000 births. 11,12 In addition to the major clinical findings mentioned previously, there are limited reports regarding the diagnosis and management of SMS with congenital scoliosis. In the present study, we reported the case of a 13-yearold SMS case with congenital scoliosis. ...
The Smith–Magenis syndrome (SMS) is a complex and rare congenital condition that is characterized by minor craniofacial anomalies, short stature, sleep disturbances, behavioral, and neurocognitive abnormalities, as well as variable multisystemic manifestations. Little is reported about spinal deformity associated with this syndrome.
This study is to present a case of scoliosis occurring in the setting of SMS and explore the possible mechanisms between the 2 diseases.
The patient is a 13-year-old Chinese female with congenital scoliosis and Tetralogy of Fallot, mental retardation, obstructive sleep apnea, hypertrophy of tonsil, conductive hearing loss, and agenesis of the epiglottis. An interphase fluorescent in situ hybridization at chromosome 17p11.2 revealed a heterozygous deletion, confirming a molecular diagnosis of SMS. She underwent a posterior correction at thoracic 1-lumbar 1 (T1-L1) levels, using the Moss-SI spinal system. At 6-month follow-up, the patient was clinically pain free and well balanced. Plain radiographs showed solid spine fusion with no loss of correction.
Congenital cardiac disease, immunodeficiency, and severe behavioral problems can affect the surgical outcome following spine fusion and need to be taken into consideration for the surgeon and anesthesiologist. Scoliosis is not uncommon among patients with SMS, and there is a potential association between congenital scoliosis and SMS. The potential mechanisms in the pathogenesis of congenital scoliosis of SMS included retinoic acid-induced 1 (RAI1) microdeletion and RAI1 gene point mutation.
... ている(e.g., Clarke & Boer, 1998;Dykens, 2004 & Smith, 1999;Edelman et al., 2007;Gamba et al., 2011;Greenberg et al., 1996;Hindenbrand & Smith, 2012) の結果を 7 項目に分類し，それぞれの発症率について， 各文献に載せられていた対象者数と該当者数に基づき再 計算を行った( , 1997;Dykens & Smith., 1998;Finucane et al., 2001;Greenberg et al., 1996;Madduri, Voigt, Llorente, Lupski, & Potocki, 2006;Martin et al., 2006;Osorio et al., 2012;Sloneem et al., 2011;Udwin et al., 2001;Wilde et al., 2013) 。知能やコミュニケーション能力の特徴について は先行研究の結果を WISC-Ⅲ (Wechsler, 1992) ・全検査 IQ：48.5(42～60；n＝22) ・言語性 IQ：53.9(47～64；n＝20)動作性 ...
... 先行研究で示された SMS のある人にみられる行動問題の発現率と他の症候群等との比較結果 注．Arron et al., 2011;Clarke & Boer, 1998;Dykens & Smith, 1998; Edelman et al., 2007;Gamba et al., 2011; Greenberg et al., 1996; Langthorn & McGill, 2012;Sarimski, 2004;Sloneem et al., 2011 を参考に筆者らが作成した。 † 印は Dykens & Smith, 1998 ...
The opportunity of continuing education for people with intellectual disabilities, graduated from secondary schools is extremely limited more than those with other disabilities. In this article, the author reviewed the history and current situations of continuing education for people with intellectual disabilities in Japan, and higher lifelong educational situations in overseas countries. In USA, recently, the opportunity of enrollment to higher education institutions has increased remarkably. While, in Japan, the nondegree graduate courses at secondary schools have gradually increased but it is still not enough. It is necessary to be pervasive them throughout the country and establish cooperation with higher education institutions and to make more appropriate educational programs. In addition, the author introduced issues about support system for students with developmental disabilities.
