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Three M Syndrome

3-M Syndrome


Presentation

  • In this report, we present four children (3 males, 1 female) from two families who were aged between 411/12 and 1011/12 years and had clinical findings of 3M syndrome.[scienceopen.com]
  • Clinical description Infants present with severe postnatal (and prenatal) growth retardation, usually associated with a low birth weight ( Etiology Mutations in the CUL7 gene (6p21.1) are most often responsible for 3M syndrome (67% of cases).[orpha.net]
  • This presents a problem when they do not or cannot eat.[silverrussellsyndrome.org]
Malocclusion
  • In addition, in some affected children, the teeth may be abnormally crowded together; as a result, the upper and lower teeth may not meet properly (malocclusion).[rarediseases.org]
Dolichocephaly
  • In most cases, premature closure of fibrous joints (sagittal sutures) between certain bones (parietal bones) of the skull may restrict lateral growth of the head, causing it to appear abnormally long and narrow (dolichocephaly).[rarediseases.org]
  • In other people with this disorder, the head has an unusually long and narrow shape (dolichocephaly). Intelligence is unaffected by 3-M syndrome, and life expectancy is generally normal.[ghr.nlm.nih.gov]
Short Fifth Finger
  • Affected individuals may have permanent fixation of certain fingers in a bent position (clinodactyly), abnormally short fifth fingers, and/or increased flexibility (hyperextensibility) of the joints.[rarediseases.org]
Large Ears
  • Infants with the disorder may also have abnormally flat cheeks and cheekbones (malar area), large ears, a prominent mouth with widely spread (patulous) lips, and/or underdeveloped upper jaw bones (maxillary hypoplasia).[rarediseases.org]
  • Other common features include large ears, full eyebrows, an upturned nose with a fleshy tip, a long area between the nose and mouth ( philtrum ), a prominent mouth, and full lips.[ghr.nlm.nih.gov]
Ear Fullness
  • Other common features include large ears, full eyebrows, an upturned nose with a fleshy tip, a long area between the nose and mouth ( philtrum ), a prominent mouth, and full lips.[ghr.nlm.nih.gov]
Suggestibility
  • We were also able to demonstrate that loss of OBSL1 leads to downregulation of CUL7, implying a role for OBSL1 in the maintenance of CUL7 protein levels and suggesting that both proteins are involved within the same molecular pathway.[scienceopen.com]
  • Diagnosis In some cases, growth retardation and/or other characteristic findings suggestive of Three M syndrome may be detected before birth (prenatally) by ultrasound.[rarediseases.org]
  • Exome sequencing identifies CCDC8 mutations in 3-M syndrome, suggesting that CCDC8 contributes in a pathway with CUL7 and OBSL1 to control human growth. Am J Hum Genet. 2011 Jul 15;89(1):148-53. doi: 10.1016/j.ajhg.2011.05.028. Epub 2011 Jul 7.[ghr.nlm.nih.gov]
Pointed Chin
  • In addition, the forehead may be abnormally prominent (frontal bossing), and the face may be triangular shaped with a prominent, pointed chin.[rarediseases.org]
  • In addition to short stature, people with 3-M syndrome have a triangle-shaped face with a broad, prominent forehead ( frontal bossing ) and a pointed chin ; the middle of the face is less prominent ( hypoplastic midface ).[ghr.nlm.nih.gov]
Frontal Bossing
  • In addition, the forehead may be abnormally prominent (frontal bossing), and the face may be triangular shaped with a prominent, pointed chin.[rarediseases.org]
  • In addition to short stature, people with 3-M syndrome have a triangle-shaped face with a broad, prominent forehead ( frontal bossing ) and a pointed chin ; the middle of the face is less prominent ( hypoplastic midface ).[ghr.nlm.nih.gov]

Workup

Delayed Bone Age
  • Additional skeletal abnormalities, such as unusually slender long bones in the arms and legs; tall, narrow spinal bones (vertebrae); or slightly delayed bone age may be apparent in x-ray images.[ghr.nlm.nih.gov]
  • Signs & Symptoms Three M syndrome is an extremely rare inherited disorder characterized by low birth weight, delayed bone age, and short stature; characteristic malformations of the head and facial (craniofacial) area; and/or finger (digital) and/or skeletal[rarediseases.org]

Treatment

  • Standard Therapies Treatment The treatment of Three M syndrome is directed toward the specific symptoms that are apparent in each individual. Treatment may require the coordinated efforts of a team of specialists.[rarediseases.org]
  • One of these patients had received growth hormone (GH) treatment which was discontinued due to an inadequate height gain.[scienceopen.com]
  • In general, the response to treatment is modest, however a trial of treatment over 1 year (GH doses of 35-45 microgram/kg/day with monitoring of serum IGF-I levels) may show a reasonable response. In this case, r-hGH should be continued long-term.[orpha.net]
  • Open surgery of the TMD is non-reversible treatment and including disc surgery (discectomy, disc repositioning), osseous surgery (artroplasty, eminectomy, eminoplasty) and TMJ reconstruction (autologous or alkoplastic-joint prosthesis).[cps.lf1.cuni.cz]
  • In addition, we have a downloadable document to assist you or your physician in the emergency care and treatment of your SRS child.[silverrussellsyndrome.org]

Prognosis

  • Prognosis 3M syndrome is not a life-threatening condition and the prognosis is good. The documents contained in this web site are presented for information purposes only.[orpha.net]

Etiology

  • Clinical description Infants present with severe postnatal (and prenatal) growth retardation, usually associated with a low birth weight ( Etiology Mutations in the CUL7 gene (6p21.1) are most often responsible for 3M syndrome (67% of cases).[orpha.net]

Epidemiology

  • Summary Epidemiology Approximately 200 cases have been reported to date but as the condition is likely under-recognized, the true figure is probably higher.[orpha.net]
Sex distribution
Age distribution

Prevention

  • Preventing Hypoglycemia During Nighttime and in Routine Daily Life: We highly encourage you to read the hypoglycemia chapter in the RSS/SRS/SGA Guidebook for comprehensive prevention and treatment information.[silverrussellsyndrome.org]
  • Mutations in the CUL7 or OBSL1 gene prevent the cullin-7 protein from bringing together the components of the E3 ubiquitin ligase complex, interfering with the process of tagging unneeded proteins for degradation.[ghr.nlm.nih.gov]

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