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Disease Profile

3M syndrome

Prevalence
Prevalence estimates on Rare Medical Network websites are calculated based on data available from numerous sources, including US and European government statistics, the NIH, Orphanet, and published epidemiologic studies. Rare disease population data is recognized to be highly variable, and based on a wide variety of source data and methodologies, so the prevalence data on this site should be assumed to be estimated and cannot be considered to be absolutely correct.

Unknown

Age of onset

Antenatal

ICD-10

Q87.1

Inheritance

Autosomal dominant A pathogenic variant in only one gene copy in each cell is sufficient to cause an autosomal dominant disease

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Autosomal recessive Pathogenic variants in both copies of each gene of the chromosome are needed to cause an autosomal recessive disease and observe the mutant phenotype

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X-linked
dominant X-linked dominant inheritance, sometimes referred to as X-linked dominance, is a mode of genetic inheritance by which a dominant gene is carried on the X chromosome.

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X-linked
recessive Pathogenic variants in both copies of a gene on the X chromosome cause an X-linked recessive disorder

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Mitochondrial or multigenic Mitochondrial genetic disorders can be caused by changes (mutations) in either the mitochondrial DNA or nuclear DNA that lead to dysfunction of the mitochondria and inadequate production of energy.

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Multigenic or multifactor Inheritance involving many factors, of which at least one is genetic but none is of overwhelming importance, as in the causation of a disease by multiple genetic and environmental factors.

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Not applicable

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Other names (AKA)

Three M syndrome; Gloomy face syndrome; 3M1;

Categories

Congenital and Genetic Diseases; Musculoskeletal Diseases

Summary

3M syndrome is a growth disorder that causes short stature, characteristic facial features, and skeletal abnormalities. Intelligence is normal.[1][2][3][4] The name comes from the initials of three researchers who first identified it: Miller, McKusick, and Malvaux.[4] 3M syndrome is caused by mutations in one of three genes: CUL7, OBSL1, and CCDC8.[1][2][3] It is inherited in an autosomal recessive pattern.[1][2][3][4] Diagnosis is based on the presence of clinical features. Genetic testing can confirm the diagnosis and identify the specific gene involved. Treatment is aimed at addressing the growth and skeletal problems and may include surgical bone lengthening, adaptive aids, and physical therapy. An endocrinologist may assist with growth hormone replacement and appropriate evaluations during puberty.[1][2]

Symptoms

This table lists symptoms that people with this disease may have. For most diseases, symptoms will vary from person to person. People with the same disease may not have all the symptoms listed. This information comes from a database called the Human Phenotype Ontology (HPO) . The HPO collects information on symptoms that have been described in medical resources. The HPO is updated regularly. Use the HPO ID to access more in-depth information about a symptom.

Medical Terms Other Names
Learn More:
HPO ID
80%-99% of people have these symptoms
Abnormality of the metaphysis
Abnormality of the wide portion of a long bone
0000944
Anteverted nares
Nasal tip, upturned
Upturned nasal tip
Upturned nose
Upturned nostrils

[ more ]

0000463
Broad forehead
Increased width of the forehead
Wide forehead

[ more ]

0000337
Bulbous nose
0000414
Delayed skeletal maturation
Delayed bone maturation
Delayed skeletal development

[ more ]

0002750
Everted lower lip vermilion
Drooping lower lip
Outward turned lower lip

[ more ]

0000232
Frontal bossing
0002007
Hypoplastic ischia
0003175
Hypoplastic pelvis
0008839
Hypoplastic pubic bone
0003173
Increased vertebral height
0004570
Intrauterine growth retardation
Prenatal growth deficiency
Prenatal growth retardation

[ more ]

0001511
Midface retrusion
Decreased size of midface
Midface deficiency
Underdevelopment of midface

[ more ]

0011800
Rocker bottom foot
Rocker bottom feet
Rocker-bottom feet
Rockerbottom feet

[ more ]

0001838
Scapular winging
Winged shoulder blade
0003691
Short neck
Decreased length of neck
0000470
Short stature
Decreased body height
Small stature

[ more ]

0004322
Slender long bone
Long bones slender
Thin long bones

[ more ]

0003100
Thick eyebrow
Bushy eyebrows
Dense eyebrow
Heavy eyebrows
Prominent eyebrows
Thick eyebrows

[ more ]

0000574
Triangular face
Face with broad temples and narrow chin
Triangular facial shape

[ more ]

0000325
30%-79% of people have these symptoms
Abnormality of dental enamel
Abnormal tooth enamel
Enamel abnormalities
Enamel abnormality

[ more ]

0000682
Abnormality of the elbow
Abnormality of the elbows
0009811
Delayed eruption of teeth
Delayed eruption
Delayed teeth eruption
Delayed tooth eruption
Eruption, delayed
Late eruption of teeth
Late tooth eruption

[ more ]

0000684
Dolichocephaly
Long, narrow head
Tall and narrow skull

[ more ]

0000268
Enlarged thorax
Wide rib cage
0100625
Horizontal ribs
0000888
Hyperlordosis
Prominent swayback
0003307
Hypoplasia of the ulna
Underdeveloped inner large forearm bone
0003022
Joint hyperflexibility
Joints move beyond expected range of motion
0005692
Long philtrum
0000343
Micromelia
Smaller or shorter than typical limbs
0002983
Pointed chin
Pointy chin
Small pointed chin
Witch's chin

[ more ]

0000307
Protruding ear
Prominent ear
Prominent ears

[ more ]

0000411
Short thorax
Shorter than typical length between neck and abdomen
0010306
Thin ribs
Slender ribs
0000883
5%-29% of people have these symptoms
Abnormality of the cerebral vasculature
Abnormality of the cerebral blood vessels
0100659
Clinodactyly of the 5th finger
Permanent curving of the pinkie finger
0004209
Congenital hip dislocation
Dislocated hip since birth
0001374
Decreased fertility
Abnormal fertility
0000144
Hypospadias
0000047
Kyphosis
Hunched back
Round back

[ more ]

0002808
Scoliosis
0002650

Treatment

The resources below provide information about treatment options for this condition. If you have questions about which treatment is right for you, talk to your healthcare professional.

Management Guidelines

  • Project OrphanAnesthesia is a project whose aim is to create peer-reviewed, readily accessible guidelines for patients with rare diseases and for the anesthesiologists caring for them. The project is a collaborative effort of the German Society of Anesthesiology and Intensive Care, Orphanet, the European Society of Pediatric Anesthesia, anesthetists and rare disease experts with the aim to contribute to patient safety.

    Organizations

    Support and advocacy groups can help you connect with other patients and families, and they can provide valuable services. Many develop patient-centered information and are the driving force behind research for better treatments and possible cures. They can direct you to research, resources, and services. Many organizations also have experts who serve as medical advisors or provide lists of doctors/clinics. Visit the group’s website or contact them to learn about the services they offer. Inclusion on this list is not an endorsement by GARD.

    Organizations Supporting this Disease

      Organizations Providing General Support

        Learn more

        These resources provide more information about this condition or associated symptoms. The in-depth resources contain medical and scientific language that may be hard to understand. You may want to review these resources with a medical professional.

        Where to Start

        • Genetics Home Reference (GHR) contains information on 3M syndrome. This website is maintained by the National Library of Medicine.
        • The National Organization for Rare Disorders (NORD) has a report for patients and families about this condition. NORD is a patient advocacy organization for individuals with rare diseases and the organizations that serve them.

          In-Depth Information

          • GeneReviews provides current, expert-authored, peer-reviewed, full-text articles describing the application of genetic testing to the diagnosis, management, and genetic counseling of patients with specific inherited conditions.
          • The Monarch Initiative brings together data about this condition from humans and other species to help physicians and biomedical researchers. Monarch’s tools are designed to make it easier to compare the signs and symptoms (phenotypes) of different diseases and discover common features. This initiative is a collaboration between several academic institutions across the world and is funded by the National Institutes of Health. Visit the website to explore the biology of this condition.
          • Online Mendelian Inheritance in Man (OMIM) lists the subtypes and associated genes for 3M syndrome in a table called Phenotypic Series. Each entry in OMIM includes a summary of related medical articles. It is meant for health care professionals and researchers. OMIM is maintained by Johns Hopkins University School of Medicine.
          • Orphanet is a European reference portal for information on rare diseases and orphan drugs. Access to this database is free of charge.
          • PubMed is a searchable database of medical literature and lists journal articles that discuss 3M syndrome. Click on the link to view a sample search on this topic.

            References

            1. Holder-Espinasse M. 3-M Syndrome. GeneReviews. January 26, 2012; https://www.ncbi.nlm.nih.gov/books/NBK1481/.
            2. Clayton P, Murray P. 3M syndrome. Orphanet. February 2014; https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=en&Expert=2616.
            3. Murray PG, Hanson D, Coulson T, Stevens A, Whatmore A, Poole RL, Mackay DJ, Black GC, Clayton PE. 3-M syndrome: a growth disorder associated with IGF2 silencing. Endocr Connect. 2013 Nov 11; 2(4):225-35. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3847915/.
            4. 3-M syndrome. Genetics Home Reference (GHR). June 2008; https://ghr.nlm.nih.gov/condition/3-m-syndrome.