Three M Syndrome 2

Alternative Names

  • 3M2
  • 3M Syndrome 2

Associated Genes

Obscurin-Like 1
Back to search Result
WHO-ICD-10 version:2010

Congenital malformations, deformations and chromosomal abnormalities

Other congenital malformations

OMIM Number

612921

Mode of Inheritance

Autosomal recessive

Gene Map Locus

2q35

Description

3M syndrome is a rare autosomal recessive disorder that combines intrauterine growth retardation (IUGR) and postnatal growth retardation. Additionally, this syndrome is characterized by dysmorphic facial features (large head, dolichocephaly, frontal bossing, a triangular face, long philtrum and hypoplastic midface) and certain radiological abnormalities. The latter includes slender long bones and ribs, foreshortened vertebral bodies, and small pelvis. The name of this disorder comes from the initials of the three researchers (Miller, McKusik and Malvaux) who first identified it. The characteristic radiologic findings of 3M syndrome are used to rule out similar disorders such as Silver-Russel syndrome (SRS), particularly the lack of limb length asymmetry that is present in over half of those with autosomal recessive SRS. The severity of symptoms and physical features varies considerably from case to case.

Mutations leading to 3M syndrome-2 were mapped to the OBSL1 gene, which encodes a putative cytoskeletal adaptor protein. The OBSL1 gene is also involved in maintaining normal levels of CUL7, which plays a role in chondrocyte growth and proliferation. This explains the main feature of 3M syndrome; retarded growth. However, there are certain consanguineous families with 3M syndrome who have neither CUL7 nor OBSL1 mutations, which indicates that there is at least one further locus that is causing this growth disorder.

Epidemiology in the Arab World

View Map
Subject IDCountrySexFamily HistoryParental ConsanguinityHPO TermsVariantZygosityMode of InheritanceReferenceRemarks
612921.1.1OmanMaleYesYes Intrauterine growth retardation; Short...NM_015311.3:c.1119G>CHomozygousAutosomal, RecessiveAkawi et al. 2011 Emirati family of om...
612921.1.2OmanMaleYesYes Intrauterine growth retardation; Short...NM_015311.3:c.1119G>CHomozygousAutosomal, RecessiveAkawi et al. 2011 Sibling of 612921.1....
612921.1.3OmanFemaleYesYes Intrauterine growth retardation; Short...NM_015311.3:c.1119G>CHomozygousAutosomal, RecessiveAkawi et al. 2011 Sibling of 612921.1....
612921.2.1JordanFemaleYesYes Intrauterine growth retardation; Short ...NM_015311.3:c.682insTT, NM_015311.3:c.690delCHomozygousAutosomal, RecessiveAkawi et al. 2011
612921.2.2JordanMaleYesYes Intrauterine growth retardation; Short ...NM_015311.3:c.682insTT, NM_015311.3:c.690delCHomozygousAutosomal, RecessiveAkawi et al. 2011 Sibling of 612921.2....
612921.2.3JordanMaleYesYes Intrauterine growth retardation; Short ...NM_015311.3:c.682insTT, NM_015311.3:c.690delCHomozygousAutosomal, RecessiveAkawi et al. 2011 Sibling of 612921.2....
612921.3Saudi ArabiaFemaleYes Joint laxity; Severe short stature; Abno...NM_015311.3:c.1306delHomozygousAutosomal, RecessiveAl-Dosari et al. 2012; Maddirevula et al. 2018
612921.4.1Saudi ArabiaMaleYesYes Joint laxity; Intrauterine growth retard...NM_015311.3:c.1306delHomozygousAutosomal, RecessiveAl-Dosari et al. 2012; Maddirevula et al. 2018
612921.4.2Saudi ArabiaFemaleYesYes Joint laxity; Intrauterine growth retard...NM_015311.3:c.1306delHomozygousAutosomal, RecessiveAl-Dosari et al. 2012; Maddirevula et al. 2018 Sibling of 612921.4....
612921.5Saudi ArabiaMaleYesYes Anteverted nares; Depressed nasal bridge...NM_015311.3:c.951C>AHomozygousAutosomal, RecessiveMaddirevula et al. 2018
612921.G.1Saudi ArabiaYesYes Short statureNM_015311.3:c.1306delHomozygousAutosomal, RecessiveMaddirevula et al. 2018 Three related patien...
612921.G.2Saudi ArabiaMaleYesYes Ulcerative colitis; Bloody diarrhea; Sho...NM_015311.3:c.268_642delHomozygousAutosomal, RecessiveMaddirevula et al. 2018 Three related patien...

Other Reports

Saudi Arabia

Al-Dosari et al. (2012) characterized a cohort of 14 patients 3M syndrome born to six consanguineous Saudi families (A-F). Genomic DNA analysis revealed that patients of families D and E shared a novel homozygous identical mutation of 1bp deletion in exon 3 of OBSL1 (c.1306del, p.Arg436Glyfs*14). The affected group included a 5.5-year-old girl and a 9-month-old boy from family D, who both received a diagnosis of severe intrauterine growth retardation, which persisted in the form of severe proportionate short stature postnatally. In family E, the index case was a 9.5-year-old girl of normal intelligence with severe proportionate short stature. Despite their typical and easily discernible clinical phenotype, all these patients have been extensively investigated for alternative causes of their short stature and received erroneous diagnoses. Al-Dosari et al. (2012) emphasized that increased awareness about this syndrome among pediatricians and endocrinologists is needed to avoid a costly and unnecessary diagnostic odyssey.

© CAGS 2024. All rights reserved.