What is Mulibrey Nanism (MUL)?
Mulibrey Nanism is a very rare genetic syndrome characterized by extreme and severe growth delays as well as abnormalities of the muscles, liver, brain, and eyes. There are 110 cases of the syndrome reported worldwide, with the majority of these cases occurring in Finland.
This syndrome is also known as:
Muscle-liver-brain-eye Nanism; Perheentupa Syndrome; Pericardial Constriction and Growth Failure
What gene changes cause Mulibrey Nanism (MUL)?
A change in the TRIM37 gene is responsible for causing the syndrome. It is inherited in an autosomal recessive pattern.
Autosomal recessive inheritance means an affected individual receives one copy of a mutated gene from each of their parents, giving them two copies of a mutated gene. Parents, who carry only one copy of the gene mutation will not generally show any symptoms but have a 25% chance of passing the copies of the gene mutations onto each of their children.
What are the main symptoms of Mulibrey Nanism (MUL)?
The main symptom of the syndrome is growth failure that begins before birth. In infancy, the main symptoms include low muscle tone and a triangular-shaped face. Symptoms affecting the eyes include a yellow discoloration deep into the eyes, although this has no impact on vision. Other symptoms include a high-pitched cry.
Most individuals with the syndrome will have what is known as a J-shaped sella turcica. This is a depression in a specific bone (the sphenoid bone) located at the base of the skull.
Constrictive pericarditis is a condition present with the syndrome. It is caused when the fibrous sac around the heart experiences an overgrowth. The condition is usually identified by the bluish discoloration of the lips and fingertips but it may affect other parts of the skull too.
The syndrome also affects parts of the body which may eventually lead to congestive heart failure. This includes prominent veins in the neck, congestion in the lungs, fluid accumulation in the stomach, swelling of the arms and lefts, as well as enlargement of the heart and/ or liver. Other possible medical conditions include elevated pressure in the veins, congestion in the pulmonary artery which serves the lungs, as well as the potential build-up of fibrous tissue in the walls of the lungs.
Another symptom includes the underdevelopment of endocrine glands which in turn leads to hormone deficiencies. This can lead to delayed puberty as well as an increased risk of premature ovarian failure and tumors in affected females. Individuals are also at increased risk for Type 2 diabetes and Wilms tumor occurs frequently with the syndrome.
Possible clinical traits/features:
Congestive heart failure, Decreased body weight, Dental crowding, Dysarthria, Dolichocephaly, Ventriculomegaly, Nevus, Nephroblastoma, Intellectual disability, Intrauterine growth retardation, Muscular hypotonia, Myocardial fibrosis, Microglossia, J-shaped sella turcica, Autosomal recessive inheritance, Pericardial constriction, Pigmentary retinopathy, Frontal bossing, Strabismus, Weak voice, Reduced tendon reflexes, Macrocephaly, Triangular face, Astigmatism, Wide nasal bridge, Absent frontal sinuses, High pitched voice, Short stature, Hepatomegaly, Depressed nasal bridge, Hypodontia, Hypoplastic frontal sinuses, Hypertelorism.
How is it diagnosed?
To find out if someone has a diagnosis of Mulibrey Nanis (MUL), it is important to have a consultation and evaluation with a clinical genetic specialist. Specialists may also suggest specific genetic testing or other types of tests to help reach a diagnosis. FDNA’s AI technology can help speed up the diagnostic process by analyzing facial features and other health information.
