Mulibrey Nanism – Definition
Mulibrey (muscle, liver, brain, and eye) nanism (MUL; OMIM #253250) is a rare autosomal recessive growth disorder that begins prenatally and is associated with severe growth retardation, a prominent face, constrictive pericarditis, hepatomegaly, male infertility, insulin resistance, and metabolic changes. There is an increased risk of Wilms’ and other tumors.
Synonyms:
Pericardial constriction and growth disturbance; perheentupa syndrome
Gene:
TRIM37
Gene product:
TRIM37
Function:
TRIM37 is an H2A ubiquitin ligase that regulates tumor suppressors and other genes.
Pattern of inheritance:
Autosomal recessive
Prevalence:
Extremely rare; in some regions, such as Finland, somewhat more common
Genotype-phenotype correlation:
Unknown
Penetrance:
Unknown
Mulibrey Nanism – Diagnosis
Diagnosis
The diagnosis is made clinically and confirmed with gene analysis by identification of a biallelic mutation in TRIM37.
Differential Diagnoses
- Silver-Russell syndrome
- 3M syndrome
Clinical Presentation
Clinical Presentation
Dwarfism is usually already apparent prenatally and continues postnatally through restricted growth. Bone changes may occur during early childhood, such as skinny, long bones with a thick cortex and a narrow medullary canal, fibrous dysplasia of the long bones, a J-shaped sella turcica, and scaphocephaly. The face of children with Mulibrey nanism is often triangular in shape, with a high and broad forehead and a flat nasal bridge, and there may be yellowish spots in the middle peripheral area of the retina and a high-pitched voice. Other abnormalities during early childhood may include hepatomegaly, cutaneous naevi flammei, pericardial constriction, feeding problems, pneumonia, and recurring respiratory infections.
Benign and malignant tumors: Cysts in various organs, peliosis of the liver, adrenal adenomas, parathyroid adenomas, thyroid nodules, cystic adenomas, renal angiomyolipoma, ovarian fibrothecoma, pheochromocytoma, and Langerhans cell histiocytosis of the CNS. Nephroblastomas, papillary renal cell carcinomas, papillary and medullary thyroid carcinomas, ovarian carcinomas, endometrial carcinoma, and acute lymphoblastic leukemia.
Special Features of Treatment
Due to the complex clinical presentation, therapy should be undertaken by a multidisciplinary team.
Diagnosis Mulibrey Nanism- What's Next?
Once diagnosed, it is recommended that a cancer predisposition specialist manage the patient. The following section explains whether cancer screening tests or other measures are necessary and how they should be performed. Some additional information, including links to support groups, is also included at the end of this page.
Diagnosis of Mulibrey Nanism - What's Next?
Once diagnosed, it is recommended that a cancer predisposition specialist manage the patient. The following section explains whether cancer screening tests or other measures are necessary and how they should be performed. Some additional information, including links to support groups, is also included at the end of this page.
Recommendations for Early Detection in Your Patients
According to the latest AACR guidelines, the following screening tests are recommended for patients with Mulibrey Nanism:
- Clinical examination every 6 months
- Wilms tumour: Sonography of the kidneys every 3 months from birth until the 7th birthday
- Hepatoblastoma: Abdominal sonography and AFP determination every 3 months from birth until the 3rd birthday
- Early detection in adults: Examination (e.g., by sonography) of the thyroid, kidneys, ovaries, and endometrium may be considered
