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 malformations.
In most cases, infants with Three M syndrome are unusually small and have a low birth weight despite being carried to term. This is due to growth delays during fetal development (intrauterine growth retardation). Growth delays and immature bone development (growth retardation and delayed bone maturation) typically continue after birth (postnatally), leading to Short stature (dwarfism) with proportional development of the arms and legs (as opposed to Short stature with abnormally small arms and legs [short-limbed dwarfism]).
Many affected infants also have distinctive abnormalities of the head and facial (craniofacial) area. 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). In addition, the forehead may be abnormally prominent (frontal bossing), and the face may be triangular shaped with a prominent, pointed chin. 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). In addition, in some cases, the teeth may be abnormally crowded together, particularly toward the front of the mouth (anterior crowding); as a result, the upper and lower teeth may not meet properly (malocclusion).
In many infants with Three M syndrome, the neck may be abnormally short and wide, the muscles that cover the upper, back portion of the neck and shoulders (trapezius muscles) may be unusually large and prominent, and the shoulders may appear square and high with wide, flared shoulder blades (winged scapulae). In many cases, affected individuals may also have additional skeletal malformations. For example, the shafts of the long bones (diaphyses) of the arms and legs may be abnormally slender, a condition that tends to become more pronounced with age. The ribs may be narrow, with abnormal, thin depressions (grooves) above their edges (costal margins). Due to abnormalities of the elongated bone forming the middle portion of the chest (sternum), the chest may be abnormally short and/or may appear sunken (pectus excavatum) or unusually prominent (pectus carinatum). Affected infants may also have malformations of bones of the spinal column (vertebrae) including abnormally long, thin vertebrae. In some cases, additional Skeletal malformations may include abnormal smallness of bones of the hips (ischium) and the pubic area. In a few cases, affected infants may have a malformation of the spinal column in which incomplete closure of certain vertebrae leaves a portion of the spinal cord exposed (spina bifida). (For more information on this condition, please choose “Spina Bifida” as your search term in the Rare Disease Database.)
In some cases, individuals with Three M syndrome may have additional abnormalities. 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.
In some cases, individuals who carry a single copy of the disease gene for Three M syndrome (heterozygotes) may exhibit some of the physical findings associated with the disorder. Such findings are typically milder than those associated with full expression of the disorder. Such individuals (heterozygotes) may exhibit subtle craniofacial abnormalities, abnormally thin bones, and/or unusually prominent ankle bones (talus).