3M syndrome is a rare autosomal recessive disorder that combines intrauterine growth retardation (IUGR) and postnatal growth retardation. Additionally, this syndrome is characterized by dysmorphic facial features (large head, dolichocephaly, frontal bossing, a triangular face, long philtrum and hypoplastic midface) and certain radiological abnormalities. The latter include slender long bones and ribs, foreshortened vertebral bodies, and small pelvis. The name of this disorder comes from the initials of the three researchers (Miller, McKusik, and Malvaux) who first identified it.
The characteristic radiologic findings of 3M syndrome are used to rule out similar disorders such as Silver-Russel syndrome (SRS), particularly the lack of limb length asymmetry that is present in over half of those with autosomal recessive SRS. The severity of symptoms and physical features varies considerably from case to case. Prenatal diagnosis is possible by ultrasonography. Supplying growth hormone to patients can help to increase body height.
[See: United Arab Emirates > Akawi et al., 2011].
Al-Dosari et al. (2012) characterized a cohort of 14 patients 3M syndrome born to six consanguineous Saudi families (A-F). They identified three CUL7 mutations that resulted in a remarkably similar clinical phenotype in two sisters (4 and 2 years old, respectively) in family A, a 4-year-old girl and her 14-month-old brother born to healthy second-cousin Saudi parents in family B, and in four patients, including an 8-year-old boy, from family C. Despite their typical and easily discernible clinical phenotype, all these patients have been extensively investigated for alternative causes of their short stature and received erroneous diagnoses. Al-Dosari et al. (2012) emphasized that increased awareness about this syndrome among pediatricians and endocrinologists is needed to avoid a costly and unnecessary diagnostic odyssey.
Akawi et al. (2011) presented the case of a Jordanian family with three affected children from first-cousin parents. The patients were one girl and two boys who suffered IUGR, postnatal short stature and feeding problems. They all showed numerous dysmorphisms, such as triangular face with prominent forehead, large eyes, depressed nasal bridge, thin upper lip, short neck, and bilateral clinodactyly. Molecular analysis revealed a nonsense mutation in the CUL7 gene, a c.203G>A leading to p.W68X. This mutation results in a truncated transcript that most probably would not pass (NMD) surveillance. Similarly, since mutations in CUL7 are associated with 3M syndrome, these patients were deemed to have 3M as opposed to Silver-Russell syndrome.