Mulibrey Nanism

Mulibrey nanism is a rare genetic disorder characterized by profound growth delays and distinctive abnormalities of the muscles, liver, brain, and eyes. The acronym MULIBREY stands for (MU)scle, (LI)ver, (BR)ain, and (EY)e; nanism is another word for dwarfism. Signs and symptoms of the disorder may include constrictive pericarditis; low birth weight; short stature; severe progressive growth delays; hypotonia; hepatomegaly; and yellow discoloration of the eyes in infancy. It is caused by mutations in the TRIM37 gene and is inherited in an autosomal recessive manner. Treatment may include surgery for constrictive pericarditis, medications for progressive heart failure and hormone replacement therapy.^[1]

Mulibrey nanism (MN) is characterized by progressive growth failure that begins prenatally (before birth). Hypotonia (poor muscle tone) is common. Newborns often have characteristic abnormalities of the head and face, including a triangularly shaped face. Yellow discoloration of the eyes and other ocular abnormalities may be present, but vision is usually normal. More than 90 percent of affected individuals have a J-shaped sella turcica, which is a depression in the sphenoid bone at the base of the skull. Infants with mulibrey nanism may also have symptoms related to overgrowth of the fibrous sac surrounding the heart (constrictive pericarditis). When constrictive pericarditis is present at birth, affected infants may have a bluish discoloration of the skin (cyanosis), especially on the lips and fingertips.^[1]

Individuals with MN typically have a high-pitched voice. Other symptoms may include abnormally prominent veins in the neck, congestion in the lungs, abnormal fluid accumulation in the abdomen (ascites), swelling of the arms and/or legs (peripheral edema), and/or enlargement of the heart (cardiac hypertrophy) and/or liver (hepatomegaly). There may also be elevated pressure in the veins, congestion or blockage in the main artery serving the lungs (pulmonary artery), and/or a build-up of fibrous tissue in the walls of the lungs (pulmonary fibrosis). Associated complications of these conditions may lead to congestive heart failure.^[1]

In some cases, individuals with mulibrey nanism may have additional physical abnormalities, such as an unusually thin shinbone (fibrous tibia dysplasia). Large cerebral ventricles in the brain and delayed motor development are uncommon findings. Most affected individuals have normal intelligence. Individuals with mulibrey nanism often have underdevelopment of various endocrine glands, that leads to hormone deficiencies. Delayed puberty sometimes occurs, accompanied by infrequent or very light menstrual periods. Females have an increased risk for premature ovarian failure and ovarian tumors.^[1]

Differences in the nature and severity of the wide range of abnormalities and complications make it difficult to predict the course of the disorder in any one individual. Some individuals may be more mildly affected, while others experience severe complications. Episodes of respiratory failure induced by an infection, as well as congestive heart failure, have occurred in infants (in addition to older individuals) with the disorder and may cause early death. It has been suggested that constrictive pericarditis with restrictive cardiomyopathy, when present, plays a large part in the prognosis. Because the heart involvement is critical for the prognosis, early diagnosis is usually of major importance.^[2]

In a study published in the New England Journal of Medicine in 2004, the authors reported that their study indicates that premature ovarian failure and infertility ultimately develop in female patients with mulibrey nanism.^[3]  A review of the available literature does not yield specific information about whether males with the disorder have infertility.

Testing for the TRIM37 gene is available for carrier testing, confirming the diagnosis, and prenatal diagnosis. GeneTests lists the names of laboratories that are performing genetic testing for mulibrey nanism. To view the contact information for the clinical laboratories conducting testing, click here. Please note that most of the laboratories listed through GeneTests do not accept direct contact from patients and their families; therefore, if you are interested in learning more, you will need to work with a health care provider or a genetics professional.

To find a medical professional who specializes in genetics, you can ask your doctor for a referral or you can search for one yourself. Online directories are provided by GeneTests, the American College of Medical Genetics, and the National Society of Genetic Counselors. If you need additional help, contact a GARD Information Specialist. You can also learn more about genetic consultations from Genetics Home Reference.