Differential diagnosis of Smith-Magenis syndrome: 1p36 deletion syndrome

Smith–Magenis syndrome (SMS; OMIM 182290) is a complexdisorder with an estimated incidence of approximately1:15,000–25,000 births [Greenberg et al., 1991]. The syndrome istypically caused by a large deletion on 17p11.2 that encompassesmultiplegenesincludingtheretinoicacid-induced1,RAI1,geneoramutationintheRAI1gene[Slageretal.,2003;Vlangosetal.,2003].The phenotype associated with SMS is characterized by a specificcombination of clinical features including variable intellectualdisability, sleep disturbance, craniofacial and skeletal anomalies,self-injurious and attention-seeking behaviors, and speech andmotor delay [Smith et al., 2005, 2010; Elsea and Girirajan, 2008].SMS is often under-diagnosed as its clinical features overlap withother intellectual disability syndromes as Prader–Willi, Williams,and Down syndromes, and 1p36 deletion syndrome.The 1p36 deletion syndrome was described in 1997 by Shapiraetal.Ithasanestimatedfrequencyof1in5,000–10,000birthsandiscaused by monosomy at chromosome 1p36 [Shapira et al., 1997;Shaffer and Lupski, 2000]. The phenotype associated with thiscontiguousgenedeletionsyndromeischaracterizedbyintellectualdisability, hypotonia, distinctive facies (deep-set eyes, prominentchin, flat nasal bridge, and asymmetric ears), and growth retarda-tion.Thesizeofthedeletionandthelocationofbreakpointsvaryineachfamilyandseemtobecorrelatedwiththephenotype[Heilstedtet al., 2003; Yu et al., 2003; Battaglia et al., 2008; Tsuyusaki et al.,2010].Recently, monosomy of 1p36.32–p36.33 was detected in apatient with Smith–Magenis-like phenotype without a deletion ormutationoftheRAI1gene[Williamsetal.,2010].Thepatientwiththe 1p36 deletion reportedly had sleep difficulties, learning andbehavioralproblemsaswellasshortstature,obesity,prognathism,dental abnormalities, brachydactyly, scoliosis, eye abnormalities,chronicearandrespiratoryinfections,andself-injuriousbehavior.SMSand1p36deletionsyndromeshowanoverlapofsomeclinicalfeatures, such as midface hypoplasia, deep-set eyes, intellectualdisability, speech delay, hypotonia, and behavior problems. How-ever,thereisnopreviousreportintheliteratureofthetypeofsleepdisordersnotedcommonlyinSMScasesoccurringinpatientswiththe 1p36 deletion. A comparison between SMS features and 1p36deletion syndrome features is shown (Table I).We present a female case (Fig. 1) with a 1p36 deletion whoseclinical features are consistent with SMS, but lacked 17p11.2deletion or a mutation in the RAI1 gene (data not shown). ThisstudywasapprovedbytheResearchEthicsCommitteeofBotucatuMedical School, S~ao Paulo State University/UNESP, Brazil.The patient is a 15-year-old female, born at term after anuncomplicatedpregnancytohealthy,nonconsanguineousparents.Her birth weight was 3,180g (50th centile) and birth length was50cm(50thcentile).Herheadcircumferencewasnotrecorded.Thepatienthaddysmorphiccraniofacialfeatures,developmentaldelay,speechdelay,infantilehypotonia,sleepdisturbance,seizures,dentalanomalies, and behavior problems. The diagnosis of SMS in thispatient was initially considered because the patient has a broad,