Congenital cardiac abnormalities such as valvular defects, septal anomalies, and tetralogy of Fallot identifiable by echocardiographic changes have also been reported. 9 Less frequently seen features include cleft lip/palate, renal/urinary tract abnormalities, thyroid dysfunction, and seizures. Neurobehavioral abnormalities in SMS become more pronounced with age and are characterized by hyperactivity, temper tantrums, attention-seeking, self-hugging, polyembolokoilamania (insertion of objects into bodily orifices), and onychotillomania (pulling out fingernails and toenails). 3, 10, 11 Infancy and childhood are associated with failure to thrive, hypotonia, and feeding difficulties. Hoarse deep voice, hearing loss, and other otolaryngologic problems such as vocal cord nodules and polyps are common. 2 Up-slanting palpebral fissures, deep-set eyes, short full-tipped nose, and downturned corners of the mouth are also seen in the majority of patients with SMS. 6– 9 Facial features consist of a broad, square-shaped face with brachycephaly, midface hypoplasia, tented upper lip, and micrognathia in early infancy progressing to prognathism with age. 5, 6 Behavioral abnormalities include significant sleep disturbances with inverted circadian rhythm of melatonin and maladaptive and self-injurious behaviors. 1– 4 The SMS phenotype includes distinctive craniofacial and skeletal features, global developmental delay, cognitive impairment, and mild to moderate mental retardation. Smith-Magenis syndrome (SMS) (Online Mendelian Inheritance in Man 182290) is a multiple congenital anomalies and mental retardation syndrome associated with either an interstitial deletion involving 17p11.2 (including RAI1) or a mutation in the RAI1 gene. Further, patients with smaller deletions show features similar to those with RAI1 mutations.Ĭonclusion: Although RAI1 is the primary gene responsible for most features of SMS, other genes within 17p11.2 contribute to the variable features and overall severity of the syndrome. Phenotypic comparison between patients with deletions and patients with RAI1 mutations show that 21 of 30 SMS features are the result of haploinsufficiency of RAI1, whereas cardiac anomalies, speech and motor delay, hypotonia, short stature, and hearing loss are associated with 17p11.2 deletions rather than RAI1 mutations ( P<.05). Ten patients with nondeletion harbored a heterozygous mutation in RAI1. Results: In our cohort, 8 of 31 individuals carried a common 3.5 Mb deletion, whereas 10 of 31 individuals carried smaller deletions, two individuals carried larger deletions, and one individual carried an atypical 17p11.2 deletion. Methods: Patients with SMS were evaluated by fluorescence in situ hybridization and/or sequencing of RAI1 to identify 17p11.2 deletions or intragenic mutations, respectively, and were compared for 30 characteristic features of this disorder by the Fisher exact test. We report the molecular and genotype–phenotype analyses of 31 patients with SMS who carry 17p11.2 deletions or mutations in the RAI1 gene. Purpose: Smith-Magenis syndrome (SMS) is a complex disorder that includes mental retardation, craniofacial and skeletal anomalies, and behavioral abnormalities.
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