Details of Disease

General Information of Disease (ID: DISRMNLQ)

• Disease Name: Dubowitz syndrome
• Synonyms: intrauterine growth retardation, short stature, microcephaly, mild mental retardation with behavior problems, eczema, and unusual and distinctive faci; dwarfism-eczema-peculiar facies syndrome; intrauterine growth retardation, short stature, microcephaly, mild mental retardation with behaviour problems, eczema, and unusual and distinctive faci; intrauterine growth retardation, short stature, microcephaly, mild intellectual disability with behavior problems, eczema, and unusual and distinctive faci; intrauterine growth retardation, short stature, microcephaly, mild intellectual disability with behaviour problems, eczema, and unusual and distinctive faci; Dubowitz syndrome; Dubowitz's syndrome
• Definition: A rare multiple congenital syndrome characterized primarly by growth retardation, microcephaly, distinctive facial dysmorphism, cutaneous eczema, a mild to severe intellectual deficit and genital abnormalities.
• Disease Hierarchy:
  DISLRS4M: Ectodermal dysplasia
  DISDOXWZ: Multiple congenital anomalies/dysmorphic syndrome-intellectual disability
  DISRMNLQ: Dubowitz syndrome
• Disease Identifiers:
  MONDO ID: MONDO_0009124
  MESH ID: C535718
  UMLS CUI: C0175691
  OMIM ID: 223370
  MedGen ID: 59797
  Orphanet ID: 235
  SNOMED CT ID: 2593002

Molecular Interaction Atlas (MIA) of This Disease

This Disease Is Related to 2 DTT Molecule(s)

Gene Name	DTT ID	Evidence Level	Mode of Inheritance	REF
PTPN11	TT7WUAV	Strong	Biomarker	[1]
RAF1	TTAN5W2	Strong	Biomarker	[2]

This Disease Is Related to 6 DOT Molecule(s)

Gene Name	DOT ID	Evidence Level	Mode of Inheritance	REF
LIG4	OT40DNXU	Supportive	Autosomal recessive	[3]
NSUN2	OTZCNM33	Supportive	Autosomal recessive	[4]
LZTR1	OTIDM6XO	Strong	Biomarker	[5]
PLXNA1	OTN0BING	Strong	Genetic Variation	[6]
RIT1	OTVNOGOH	Strong	Biomarker	[7]
SOS1	OTTCWXC3	Strong	Biomarker	[8]

References

• [1] Mouse model of Noonan syndrome reveals cell type- and gene dosage-dependent effects of Ptpn11 mutation.Nat Med. 2004 Aug;10(8):849-57. doi: 10.1038/nm1084. Epub 2004 Jul 25.
• [2] Increased BRAF heterodimerization is the common pathogenic mechanism for noonan syndrome-associated RAF1 mutants.Mol Cell Biol. 2012 Oct;32(19):3872-90. doi: 10.1128/MCB.00751-12. Epub 2012 Jul 23.
• [3] Dubowitz syndrome is a complex comprised of multiple, genetically distinct and phenotypically overlapping disorders. PLoS One. 2014 Jun 3;9(6):e98686. doi: 10.1371/journal.pone.0098686. eCollection 2014.
• [4] Whole exome sequencing identifies a splicing mutation in NSUN2 as a cause of a Dubowitz-like syndrome. J Med Genet. 2012 Jun;49(6):380-5. doi: 10.1136/jmedgenet-2011-100686. Epub 2012 May 10.
• [5] Mutations in LZTR1 drive human disease by dysregulating RAS ubiquitination.Science. 2018 Dec 7;362(6419):1177-1182. doi: 10.1126/science.aap7607. Epub 2018 Nov 15.
• [6] PLXNA1 developmental encephalopathy with syndromic features: A case report and review of the literature.Am J Med Genet A. 2017 Jul;173(7):1951-1954. doi: 10.1002/ajmg.a.38236. Epub 2017 May 2.
• [7] New Noonan syndrome model mice with RIT1 mutation exhibit cardiac hypertrophy and susceptibility to -adrenergic stimulation-induced cardiac fibrosis.EBioMedicine. 2019 Apr;42:43-53. doi: 10.1016/j.ebiom.2019.03.014. Epub 2019 Mar 18.
• [8] Activation of multiple signaling pathways causes developmental defects in mice with a Noonan syndromeassociated Sos1 mutation.J Clin Invest. 2010 Dec;120(12):4353-65. doi: 10.1172/JCI43910.