Definition

Mulibrey (muscle, liver, brain, and eye) nanism (MUL; OMIM #253250) is a rare autosomal-recessive growth disorder that already starts prenatally and is associated with a severe growth disorder, a striking facial appearance, constrictive pericarditis, hepatomegaly, male infertility, insulin resistance, and metabolic changes. There is an increased risk of developing Wilms and other tumors.

Key Data

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Synonym Pericardial constriction and growth disorder; Perheentupa syndrome
Gene TRIM37
Gene product TRIM37
Function TRIM37 is an H2A ubiquitin ligase that regulates tumor suppressor genes and other genes.
Heredity Autosomal recessive
Prevalence Extremely rare; somewhat more common in a few regions such as Finland
Genotype-phenotype correlation Unknown
Penetrance Unknown
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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.

Therapeutic Considerations

Due to the complex clinical presentation, therapy should be undertaken by a multidisciplinary team.

Surveillance Recommendations

Surveillance Recommendations

  • Abdominal ultrasound every 3 months until the age of 7 to check for the development of Wilms tumor

  • Early detection in adults: examination of the thyroid, kidneys, ovaries, and endometrium (using ultrasound, for example)

Additional Information

Open Clinical Trials / Registries

There are currently no open clinical trials/registries for patients with Mulibrey nanism that we can recommend to you for more information.

Support Groups