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Description
3MC syndrome is a disorder characterized by unusual facial features and problems affecting other tissues and organs.
The distinctive facial features of people with 3MC syndrome include widely spaced eyes (hypertelorism), a narrowing of the eye opening (blepharophimosis), droopy eyelids (ptosis), highly arched eyebrows, and an opening in the upper lip (cleft lip) with an opening in the roof of the mouth (cleft palate).
Other common features of 3MC syndrome include developmental delay, intellectual disability, hearing loss, and slow growth after birth resulting in short stature. Less often, individuals with 3MC syndrome can have abnormal fusion of certain bones in the skull (craniosynostosis) or forearm (radioulnar synostosis); an outgrowth of the tailbone (caudal appendage); a soft out-pouching around the belly-button (an umbilical hernia); and abnormalities of the kidneys, bladder, or genitals.
3MC syndrome encompasses four disorders that were formerly considered to be separate: Mingarelli, Malpeuch, Michels, and Carnevale syndromes. Researchers now generally consider these disorders to be part of the same condition, which is called 3MC based on the initials of the older condition names.
Frequency
3MC syndrome is a rare disorder; its prevalence is unknown.
Causes
3MC syndrome is caused by mutations in the COLEC10, COLEC11, or MASP1 gene. These genes provide instructions for making proteins that are involved in a series of steps called the lectin complement pathway. This pathway is thought to help direct the movement (migration) of cells during development before birth to form the organs and systems of the body. The lectin complement pathway appears to be particularly important in directing the migration of neural crest cells. These cells give rise to various tissues including many tissues in the face and skull, the glands that produce hormones (endocrine glands), and portions of the nervous system. After birth, the lectin complement pathway is involved in the immune system.
The COLEC10, COLEC11, and MASP1 gene mutations that cause 3MC syndrome impair or eliminate the function of the corresponding proteins, resulting in faulty control of cell migration in early development. Impaired cell migration disrupts the normal growth and development of several tissues and organs, which leads to the various abnormalities that occur in this disorder. Researchers suggest that similar pathways in the immune system can compensate for problems in the lectin complement pathway, which explains why immune system abnormalities are not part of 3MC syndrome.
Inheritance
This condition is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition.
Other Names for This Condition
- Carnevale syndrome
- Carnevale-Krajewska-Fischetto syndrome
- Craniofacial-ulnar-renal syndrome
- Craniosynostosis with lid anomalies
- Malpuech facial clefting syndrome
- Malpuech syndrome
- Michels syndrome
- Mingarelli syndrome
- Oculo-skeletal-abdominal syndrome
- Oculopalatoskeletal syndrome
- OSA syndrome
- Ptosis of eyelids with diastasis recti and hip dysplasia
- Ptosis-strabismus-rectus abdominis diastasis
Additional Information & Resources
Genetic Testing Information
Genetic and Rare Diseases Information Center
Patient Support and Advocacy Resources
Catalog of Genes and Diseases from OMIM
Scientific Articles on PubMed
References
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- Munye MM, Diaz-Font A, Ocaka L, Henriksen ML, Lees M, Brady A, Jenkins D, Morton J, Hansen SW, Bacchelli C, Beales PL, Hernandez-Hernandez V. COLEC10 is mutated in 3MC patients and regulates early craniofacial development. PLoS Genet. 2017 Mar 16;13(3):e1006679. doi: 10.1371/journal.pgen.1006679. eCollection 2017 Mar. Citation on PubMed or Free article on PubMed Central
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- Selman L, Hansen S. Structure and function of collectin liver 1 (CL-L1) and collectin 11 (CL-11, CL-K1). Immunobiology. 2012 Sep;217(9):851-63. doi: 10.1016/j.imbio.2011.12.008. Epub 2012 Feb 4. Citation on PubMed
- Sirmaci A, Walsh T, Akay H, Spiliopoulos M, Sakalar YB, Hasanefendioglu-Bayrak A, Duman D, Farooq A, King MC, Tekin M. MASP1 mutations in patients with facial, umbilical, coccygeal, and auditory findings of Carnevale, Malpuech, OSA, and Michels syndromes. Am J Hum Genet. 2010 Nov 12;87(5):679-86. doi: 10.1016/j.ajhg.2010.09.018. Epub 2010 Oct 28. Citation on PubMed or Free article on PubMed Central
- Titomanlio L, Bennaceur S, Bremond-Gignac D, Baumann C, Dupuy O, Verloes A. Michels syndrome, Carnevale syndrome, OSA syndrome, and Malpuech syndrome: variable expression of a single disorder (3MC syndrome)? Am J Med Genet A. 2005 Sep 1;137A(3):332-5. doi: 10.1002/ajmg.a.30878. Citation on PubMed
- Urquhart J, Roberts R, de Silva D, Shalev S, Chervinsky E, Nampoothiri S, Sznajer Y, Revencu N, Gunasekera R, Suri M, Ellingford J, Williams S, Bhaskar S, Clayton-Smith J. Exploring the genetic basis of 3MC syndrome: Findings in 12 further families. Am J Med Genet A. 2016 May;170A(5):1216-24. doi: 10.1002/ajmg.a.37564. Epub 2016 Jan 20. Citation on PubMed
- Venkatraman Girija U, Furze CM, Gingras AR, Yoshizaki T, Ohtani K, Marshall JE, Wallis AK, Schwaeble WJ, El-Mezgueldi M, Mitchell DA, Moody PC, Wakamiya N, Wallis R. Molecular basis of sugar recognition by collectin-K1 and the effects of mutations associated with 3MC syndrome. BMC Biol. 2015 Apr 17;13:27. doi: 10.1186/s12915-015-0136-2. Citation on PubMed or Free article on PubMed Central
- Yongqing T, Wilmann PG, Reeve SB, Coetzer TH, Smith AI, Whisstock JC, Pike RN, Wijeyewickrema LC. The x-ray crystal structure of mannose-binding lectin-associated serine proteinase-3 reveals the structural basis for enzyme inactivity associated with the Carnevale, Mingarelli, Malpuech, and Michels (3MC) syndrome. J Biol Chem. 2013 Aug 2;288(31):22399-407. doi: 10.1074/jbc.M113.483875. Epub 2013 Jun 21. Erratum In: J Biol Chem. 2013 Sep 27;288(39):28307. Citation on PubMed or Free article on PubMed Central
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