Details of Disease

General Information of Disease (ID: DISE4WMQ)

• Disease Name: Wolf-Hirschhorn syndrome
• Synonyms: Wolf syndrome; microcephaly, IUGR, hypertelorism, ptosis, iris coloboma, hooked nose, external ear dysplasia, psychomotor retardation; 4p syndrome; WHS; chromosome 4P16.3 deletion syndrome; chromosome 4p syndrome; Pitt syndrome; 4p- syndrome; chromosome 4p16.3 deletion syndrome; Pitt-Rogers-Danks syndrome; Wolf-Hirschhorn syndrome; telomeric deletion 4p; distal monosomy 4p; Wolf-Hirschhorn syndrome, Isolated cases; Wittwer syndrome; 4p deletion syndrome; distal deletion 4p
• Definition: Wolf-Hirschhorn syndrome (WHS) is a developmental disorder characterized by typical craniofacial features, prenatal and postnatal growth impairment, intellectual disability, severe delayed psychomotor development, seizures, and hypotonia.
• Disease Hierarchy:
  DIS6SVEE: Syndromic disease
  DISMKJUH: Chromosome 4 short arm deletion
  DISDOXWZ: Multiple congenital anomalies/dysmorphic syndrome-intellectual disability
  DISE4WMQ: Wolf-Hirschhorn syndrome
• Disease Identifiers:
  MONDO ID: MONDO_0008684
  MESH ID: D054877
  UMLS CUI: C1956097
  OMIM ID: 194190
  MedGen ID: 408255
  Orphanet ID: 280
  SNOMED CT ID: 17122004

Molecular Interaction Atlas (MIA) of This Disease

This Disease Is Related to 3 DTT Molecule(s)

Gene Name	DTT ID	Evidence Level	Mode of Inheritance	REF
DRD5	TTS2PH3	Strong	Biomarker	[1]
IL1RL1	TT4GZA4	Strong	Biomarker	[2]
TACC3	TTQ4UFD	Strong	Biomarker	[3]

This Disease Is Related to 1 DME Molecule(s)

Gene Name	DME ID	Evidence Level	Mode of Inheritance	REF
LAP3	DENZF0O	Strong	Altered Expression	[4]

This Disease Is Related to 6 DOT Molecule(s)

Gene Name	DOT ID	Evidence Level	Mode of Inheritance	REF
FGFRL1	OT8HZ3ZL	Strong	Biomarker	[3]
MSX1	OT5U41ZP	Strong	Genetic Variation	[5]
OXA1L	OTS0BFRD	Strong	Genetic Variation	[6]
SET	OTGYYQJO	Strong	Biomarker	[7]
SLBP	OTVYYQRT	Strong	Biomarker	[8]
NSD2	OTQ6SW4R	Definitive	Autosomal dominant	[9]

References

• [1] Localization of the D5 dopamine receptor gene to human chromosome 4p15.1-p15.3, centromeric to the Huntington's disease locus.Genomics. 1992 Mar;12(3):510-6. doi: 10.1016/0888-7543(92)90442-u.
• [2] Heterozygous submicroscopic inversions involving olfactory receptor-gene clusters mediate the recurrent t(4;8)(p16;p23) translocation.Am J Hum Genet. 2002 Aug;71(2):276-85. doi: 10.1086/341610. Epub 2002 Jun 10.
• [3] Prenatal diagnosis of a 1.6-Mb 4p16.3 interstitial microdeletion encompassing FGFRL1 and TACC3 associated with bilateral cleft lip and palate of Wolf-Hirschhorn syndrome facial dysmorphism and short long bones.Taiwan J Obstet Gynecol. 2017 Dec;56(6):821-826. doi: 10.1016/j.tjog.2017.10.021.
• [4] Suggested assignment of peptidase S (PEPS) to 4p11-4q12 by exclusion using gene dosage, accounting for variability in fibroblasts.Hum Genet. 1983;64(2):134-8. doi: 10.1007/BF00327109.
• [5] MSX1 gene in the etiology orofacial deformities.Postepy Hig Med Dosw (Online). 2015 Dec 31;69:1499-504.
• [6] First known microdeletion within the Wolf-Hirschhorn syndrome critical region refines genotype-phenotype correlation.Am J Med Genet. 2001 Apr 1;99(4):338-42. doi: 10.1002/ajmg.1203.
• [7] Activated fibroblast growth factor receptor 3 is an oncogene that contributes to tumor progression in multiple myeloma.Blood. 2001 Feb 1;97(3):729-36. doi: 10.1182/blood.v97.3.729.
• [8] Characterizing the functional consequences of haploinsufficiency of NELF-A (WHSC2) and SLBP identifies novel cellular phenotypes in Wolf-Hirschhorn syndrome.Hum Mol Genet. 2012 May 15;21(10):2181-93. doi: 10.1093/hmg/dds033. Epub 2012 Feb 10.
• [9] De novo truncating variants in WHSC1 recapitulate the Wolf-Hirschhorn (4p16.3 microdeletion) syndrome phenotype. Genet Med. 2019 Jan;21(1):185-188. doi: 10.1038/s41436-018-0014-8. Epub 2018 Jun 11.