title: Gender, genotype, and phenotype differences in Smith-Magenis syndrome: a meta-analysis of 105 cases.
abstract: Smith-Magenis syndrome (SMS) is a multisystem disorder characterized by developmental delay and mental retardation, a distinctive behavioral phenotype, and sleep disturbance. We undertook a comprehensive meta-analysis to identify genotype-phenotype relationships to further understand the clinical variability and genetic factors involved in SMS. Clinical and molecular information on 105 patients with SMS was obtained through research protocols and a review of the literature and analyzed using Fisher's exact test with two-tailed p values. Several differences in these groups of patients were identified based on genotype and gender. Patients with RAI1 mutation were more likely to exhibit overeating, obesity, polyembolokoilamania, self-hugging, muscle cramping, and dry skin and less likely to have short stature, hearing loss, frequent ear infections, and heart defects when compared with patients with deletion, while a subset of small deletion cases with deletions spanning from TNFRSF13B to MFAP4 was less likely to exhibit brachycephaly, dental anomalies, iris abnormalities, head-banging, and hyperactivity. Significant differences between genders were also identified, with females more likely to have myopia, eating/appetite problems, cold hands and feet, and frustration with communication when compared with males. These results confirm previous findings and identify new genotype-phenotype associations including differences in the frequency of short stature, hearing loss, ear infections, obesity, overeating, heart defects, self-injury, self-hugging, dry skin, seizures, and hyperactivity among others based on genotype. Additional studies are required to further explore the relationships between genotype and phenotype and any potential discrepancies in health care and parental attitudes toward males and females with SMS.
authors.affiliation: Department of Human Genetics, Virginia Commonwealth University, Richmond, VA 23298, USA.
authors.forename: E A
authors.initials: EA
authors.lastname: Edelman
authors.forename: S
authors.initials: S
authors.lastname: Girirajan
authors.forename: B
authors.initials: B
authors.lastname: Finucane
authors.forename: P I
authors.initials: PI
authors.lastname: Patel
authors.forename: J R
authors.initials: JR
authors.lastname: Lupski
authors.forename: A C M
authors.initials: AC
authors.lastname: Smith
authors.forename: S H
authors.initials: SH
authors.lastname: Elsea
mesh_terms: D000015:Abnormalities, Multiple / Q000235:genetics* / Q000473:pathology; D002872:Chromosome Deletion; D002886:Chromosomes, Human, Pair 17 / Q000235:genetics*; D005260:Female; D005838:Genotype; D006801:Humans; D008607:Intellectual Disability / Q000473:pathology*; D008297:Male; D010641:Phenotype; D017354:Point Mutation; D012737:Sex Factors; D013577:Syndrome; D015534:Trans-Activators; D014157:Transcription Factors / Q000235:genetics
chemical_list: C431552:RAI1 protein, human; D015534:Trans-Activators; D014157:Transcription Factors