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.

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.

Normal Function

The COLEC10 gene provides instructions for making a protein called collectin liver 1 (CL-L1). This protein is involved in a series of steps called the lectin complement pathway, which 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, glands that produce hormones (endocrine glands), and portions of the nervous system. After birth, the lectin complement pathway is involved in the immune system.

Health Conditions Related to Genetic Changes

3MC syndrome

At least three COLEC10 gene mutations have been identified in people with 3MC syndrome, a disorder characterized by unusual facial features and a variety of problems affecting other tissues and organs. The COLEC10 gene mutations that cause 3MC syndrome impair or eliminate the function of the CL-L1 protein, resulting in faulty control of cell migration in early development and leading 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.

Other Names for This Gene

• 3MC3
• CL-34
• CL-L1
• CLL1
• collectin liver 1
• collectin liver protein 1
• collectin sub-family member 10 (C-type lectin)
• collectin-10 isoform 1 precursor
• collectin-10 isoform 2
• collectin-34

Genomic Location

Normal Function

The COLEC11 gene provides instructions for making a protein called collectin kidney 1 (CL-K1). This protein is involved in a series of steps called the lectin complement pathway, which 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, glands that produce hormones (endocrine glands), and portions of the nervous system. After birth, the lectin complement pathway is involved in the immune system.

Health Conditions Related to Genetic Changes

3MC syndrome

At least nine COLEC11 gene mutations have been identified in people with 3MC syndrome, a disorder characterized by unusual facial features and a variety of problems affecting other tissues and organs. The COLEC11 gene mutations that cause 3MC syndrome impair or eliminate the function of the CL-K1 protein, resulting in faulty control of cell migration in early development and leading 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.

Other Names for This Gene

• 3MC2
• CL-K1
• CL-K1-I
• CL-K1-II
• CL-K1-IIa
• CL-K1-IIb
• CLK1
• collectin K1
• collectin kidney protein 1
• MGC3279

Genomic Location

Normal Function

The MASP1 gene provides 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. It 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.

Proteins called MASP-1, MASP-3, and MAp44 can be produced from the MASP1 gene, depending on how the gene's instructions are pieced together. These proteins differ at one end of their structure. The MASP-1 and MASP-3 proteins have different versions of regions called serine protease domains, while the MAp44 protein has no serine protease domain. Researchers are studying whether these proteins play different roles in the lectin complement pathway.

Health Conditions Related to Genetic Changes

3MC syndrome

At least 11 MASP1 gene mutations have been identified in people with 3MC syndrome, a disorder characterized by unusual facial features and a variety of problems affecting other tissues and organs of the body. Because all of the MASP1 gene mutations that cause 3MC syndrome affect the MASP-3 protein, alterations in this protein's function are thought to account for the signs and symptoms of 3MC syndrome. Because parts of the three protein versions are the same, some of the MASP1 gene mutations affect the other protein versions in addition to affecting MASP-3.

The protein changes result in faulty control of cell migration in early development, leading 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.

Other Names for This Gene

• 3MC1
• complement factor MASP-3
• complement-activating component of Ra-reactive factor
• CRARF
• CRARF1
• mannan-binding lectin serine peptidase 1 (C4/C2 activating component of Ra-reactive factor)
• mannose-binding lectin-associated serine protease 1
• mannose-binding protein-associated serine protease
• MAP1
• MAp44
• MASP
• MASP3
• PRSS5
• Ra-reactive factor serine protease p100
• RaRF
• serine protease 5

Genomic Location

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.

3MC syndrome is a rare disorder; its prevalence is unknown.