Details of Disease

Disease Name

Smith-Magenis syndrome

Smith-Magenis chromosome region; SMS; Smith-Magenis syndrome chromosome region; chromosome 17P11.2 deletion syndrome; 17p11.2 microdeletion syndrome; Smith-Magenis syndrome, Isolated cases; chromosome 17p11.2 deletion syndrome; SMITH-Magenis syndrome; Smith Magenis Syndrome; Smith-Magenis syndrome

Definition

Smith-Magenis syndrome (SMS) is a complex genetic disorder characterized by variable intellectual deficit, sleep disturbance, craniofacial and skeletal anomalies, psychiatric disorders, and speech and motor delay.

Disease Hierarchy

DIS1DD8C: Syndrome caused by partial chromosomal deletion

DIS2BIP8: Congenital nervous system disorder

DISH7SDF: Syndromic intellectual disability

DISD715V: Hereditary neurological disease

DISDOXWZ: Multiple congenital anomalies/dysmorphic syndrome-intellectual disability

DISG4G6X: Smith-Magenis syndrome

Disease Identifiers

MONDO ID

MONDO_0008434

MESH ID

D058496

UMLS CUI

C0795864

OMIM ID

182290

MedGen ID

162881

Orphanet ID

819

SNOMED CT ID

401315004

General Information of Disease (ID: DISG4G6X)

Molecular Interaction Atlas (MIA) of This Disease

Molecular Interaction Atlas (MIA)

This Disease Is Related to 4 DTT Molecule(s)

Gene Name	DTT ID	Evidence Level	Mode of Inheritance	REF
GAD2	TT7UY6K	Strong	Biomarker	[1]
RARA	TTW38KT	Strong	Biomarker	[2]
SREBF1	TTER0UB	Strong	Biomarker	[3]
TNFRSF13B	TTL9OD4	Strong	Genetic Variation	[4]
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This Disease Is Related to 24 DOT Molecule(s)

Gene Name	DOT ID	Evidence Level	Mode of Inheritance	REF
MBD5	OTFHT4MO	moderate	Genetic Variation	[5]
CLOCK	OTNEOJY7	Strong	Genetic Variation	[6]
COPS3	OTZWPJ24	Strong	Biomarker	[7]
DEAF1	OTCLX3ZW	Strong	Genetic Variation	[8]
ENDOU	OTB7OF7Y	Strong	Biomarker	[9]
EXOSC6	OTAC10N6	Strong	Biomarker	[9]
FLCN	OTVM78XM	Strong	Genetic Variation	[10]
FLII	OT7G9JG6	Strong	Genetic Variation	[11]
IFIH1	OTZA2AHA	Strong	Biomarker	[12]
IQSEC2	OTYFRM4Q	Strong	Genetic Variation	[8]
LLGL1	OTAIQSXZ	Strong	Biomarker	[13]
MFAP4	OT5W64QY	Strong	Genetic Variation	[14]
MYO15A	OTVR4DV8	Strong	Genetic Variation	[15]
NT5M	OTJF73BA	Strong	Biomarker	[16]
NUDT10	OT61XMYC	Strong	Biomarker	[17]
PACC1	OTKBS8CC	Strong	Biomarker	[18]
PMP22	OTXWYWCZ	Strong	Genetic Variation	[19]
RASD1	OT2BAJHK	Strong	Biomarker	[3]
REM1	OTUXL0HC	Strong	Biomarker	[20]
RNF112	OT0Q9OUQ	Strong	Biomarker	[21]
RNH1	OT6EC79B	Strong	Genetic Variation	[22]
SHC3	OT305NPA	Strong	Genetic Variation	[22]
TCF20	OT8LQAOV	Strong	Biomarker	[23]
RAI1	OTKLQU00	Definitive	Autosomal dominant	[24]
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⏷ Show the Full List of 24 DOT(s)

References

1	A new solid-phase radioimmunoassay to detect anti-GAD65 autoantibodies.J Immunol Methods. 1997 Sep 24;207(2):107-13. doi: 10.1016/s0022-1759(97)00101-4.
2	Prognostic significance of equivocal human epidermal growth factor receptor 2 results and clinical utility of alternative chromosome 17 genes in patients with invasive breast cancer: A cohort study.Cancer. 2017 Apr 1;123(7):1115-1123. doi: 10.1002/cncr.30460. Epub 2016 Nov 28.
3	Multiethnic Meta-Analysis Identifies RAI1 as a Possible Obstructive Sleep Apnea-related Quantitative Trait Locus in Men.Am J Respir Cell Mol Biol. 2018 Mar;58(3):391-401. doi: 10.1165/rcmb.2017-0237OC.
4	TNF receptor superfamily member 13b (TNFRSF13B) hemizygosity reveals transmembrane activator and CAML interactor haploinsufficiency at later stages of B-cell development.J Allergy Clin Immunol. 2015 Nov;136(5):1315-25. doi: 10.1016/j.jaci.2015.05.012. Epub 2015 Jun 19.
5	MBD5 haploinsufficiency is associated with sleep disturbance and disrupts circadian pathways common to Smith-Magenis and fragile X syndromes.Eur J Hum Genet. 2015 Jun;23(6):781-9. doi: 10.1038/ejhg.2014.200. Epub 2014 Oct 1.
6	Smith-Magenis syndrome.Handb Clin Neurol. 2013;111:295-6. doi: 10.1016/B978-0-444-52891-9.00034-8.
7	Hemizygosity for the COP9 signalosome subunit gene, SGN3, in the Smith-Magenis syndrome.Am J Med Genet. 1999 Dec 3;87(4):342-8.
8	Exome analysis of Smith-Magenis-like syndrome cohort identifies de novo likely pathogenic variants. Hum Genet. 2017 Apr;136(4):409-420. doi: 10.1007/s00439-017-1767-x. Epub 2017 Feb 17.
9	Microsatellite mapping of the deletion in patients with hereditary neuropathy with liability to pressure palsies (HNPP): new molecular tools for the study of the region 17p12 --> p11 and for diagnosis.Cytogenet Cell Genet. 1996;72(1):20-5. doi: 10.1159/000134153.
10	Bilateral renal tumors in an adult man with Smith-Magenis syndrome: The role of the FLCN gene.Eur J Med Genet. 2016 Oct;59(10):499-501. doi: 10.1016/j.ejmg.2016.09.005. Epub 2016 Sep 12.
11	Diagnostic FISH probes for del(17)(p11.2p11.2) associated with Smith-Magenis syndrome should contain the RAI1 gene.Am J Med Genet A. 2005 Jan 30;132A(3):278-82. doi: 10.1002/ajmg.a.30461.
12	Singleton-Merten Syndrome-like Skeletal Abnormalities in Mice with Constitutively Activated MDA5.J Immunol. 2019 Sep 1;203(5):1356-1368. doi: 10.4049/jimmunol.1900354. Epub 2019 Jul 31.
13	The brain finger protein gene (ZNF179), a member of the RING finger family, maps within the Smith-Magenis syndrome region at 17p11.2.Am J Med Genet. 1997 Mar 31;69(3):320-4.
14	The gene for a human microfibril-associated glycoprotein is commonly deleted in Smith-Magenis syndrome patients.Hum Mol Genet. 1995 Apr;4(4):589-97. doi: 10.1093/hmg/4.4.589.
15	Novel mutations of MYO15A associated with profound deafness in consanguineous families and moderately severe hearing loss in a patient with Smith-Magenis syndrome.Hum Genet. 2001 Nov;109(5):535-41. doi: 10.1007/s004390100604. Epub 2001 Oct 3.
16	A deoxyribonucleotidase in mitochondria: involvement in regulation of dNTP pools and possible link to genetic disease.Proc Natl Acad Sci U S A. 2000 Jul 18;97(15):8239-44. doi: 10.1073/pnas.97.15.8239.
17	Comparative analysis of epitope recognition of glutamic acid decarboxylase (GAD) by autoantibodies from different autoimmune disorders.Clin Exp Immunol. 1999 Dec;118(3):349-56. doi: 10.1046/j.1365-2249.1999.01030.x.
18	Genes in a refined Smith-Magenis syndrome critical deletion interval on chromosome 17p11.2 and the syntenic region of the mouse.Genome Res. 2002 May;12(5):713-28. doi: 10.1101/gr.73702.
19	Nonrecurrent PMP22-RAI1 contiguous gene deletions arise from replication-based mechanisms and result in Smith-Magenis syndrome with evident peripheral neuropathy.Hum Genet. 2016 Oct;135(10):1161-74. doi: 10.1007/s00439-016-1703-5. Epub 2016 Jul 7.
20	Hypoventilation in REM sleep in a case of 17p11.2 deletion (Smith-Magenis syndrome).Am J Med Genet A. 2010 Mar;152A(3):708-12. doi: 10.1002/ajmg.a.32700.
21	Molecular cloning, localization, and developmental expression of mouse brain finger protein (Bfp)/ZNF179: distribution of bfp mRNA partially coincides with the affected areas of Smith-Magenis syndrome.Genomics. 1998 Nov 15;54(1):59-69. doi: 10.1006/geno.1998.5541.
22	First evidence of Smith-Magenis syndrome in mother and daughter due to a novel RAI mutation.Am J Med Genet A. 2017 Jan;173(1):231-238. doi: 10.1002/ajmg.a.37989. Epub 2016 Sep 28.
23	De novo and inherited TCF20 pathogenic variants are associated with intellectual disability, dysmorphic features, hypotonia, and neurological impairments with similarities to Smith-Magenis syndrome.Genome Med. 2019 Feb 28;11(1):12. doi: 10.1186/s13073-019-0623-0.
24	Technical standards for the interpretation and reporting of constitutional copy-number variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics (ACMG) and the Clinical Genome Resource (ClinGen). Genet Med. 2020 Feb;22(2):245-257. doi: 10.1038/s41436-019-0686-8. Epub 2019 Nov 6.