3MC Syndromes

Background and History: 

This category of disease consists of 3 or perhaps 4 conditions resulting from several gene mutations.  They have been grouped into this single entity since the clinical features for each are so similar that the correct diagnosis often cannot be make on clinical evaluation but requires identification of the specific gene mutation responsible.

Clinical Correlations: 

The facial appearance characteristically involves relatively minor cosmetic variations of periocular structures such as the eyelids and eyebrows.  The eyes themselves function normally but appear to be abnormally far apart.  The eyelids often are 'droopy' and the eyebrows are highly arched.  The tears ducts were not fully formed in one individual.

Other signs of this condition that involve other parts of the body are highly variable and few patients have all of them. Cleft lip and palate, hearing loss, intellectual ability and general growth deficiency are seen in about half of patients.  Abnormal growth of the skull, fusion of the radius and ulnar bones in the arm, and abnormalities of the genitalia and kidney system are present in one-third of individuals.  Other less common abnormalities include heart defects, and abdominal wall defects with hernial protrusion of abdominal contents.


These disorders are inherited as autosomal recessives and have a recurrence risk of 25% in families in which both parents have a specific mutation in a specific gene.  This is the risk of developing these syndromes because one in four offspring from such parental matings on average will inherit both mutations necessary to cause these 3MC syndromes.

Diagnosis and Prognosis: 

While the facial abnormalities are present at birth, they are individually nonspecific and the appearance in infants may not be recognized.  A team of pediatricians, ophthalmologists, and neurologists are likely to collaborate in the clinical evaluation.  Because of the nonspecific and overlapping physical signs the ultimate diagnosis depends upon identification of the gene mutation.

Infants and children may suffer an early demise from any number of the malformations such as heart defects.  Individual defects such as cleft lips and palates, abdominal wall defects, and skeletal deformities may be corrected surgically.  Because of the wide range of abnormalities among children with this disorder, prospective treatments usually require consensus among multiple specialties.

Additional Information
Autosomal recessive