Mulibrey Nanism: A Case with Heart Failure.

Mulibrey Nanism is a rare genetic disorder characterized by a variety of systemic manifestations, including cardiac involvement. We report the case of a 26-year-old male who underwent partial pericardiectomy for constrictive pericarditis at age 4 and presented to our cardiology clinic with heart failure symptoms. Examination revealed dysmorphic features characteristic of Mulibrey Nanism such as short stature, macrocephaly, and hypertelorism. Genetic testing identified a homozygous likely pathogenic mutation in the TRIM37 gene. The patient's heart failure was managed through a multidisciplinary approach, involving consultations with various specialties to address and diagnose the syndrome's complex multisystem pathologies. This case underscores the importance of including Mulibrey Nanism in the differential diagnosis of patients with a history of constrictive pericarditis at an early age and dysmorphic features, as well as the necessity of a multidisciplinary approach to manage the diverse manifestations of this rare genetic disorder.

CD4+ T Cell Defects in a Mulibrey Patient With Specific TRIM37 Mutations.

Mulibrey (muscle-liver-brain-eye) syndrome (MUL) is an autosomal recessive disorder caused by mutations in the TRIpartite motif (TRIM)37 gene, encoding for TRIM37 a member of the TRIM E3 ubiquitin ligase protein family. MUL patients are characterized by growth retardation, dysmorphic features, and a wide range of abnormalities affecting different organs. However, T-cell abnormalities have not been observed in MUL subjects, to date. Here we described the immunological features of a MUL child carrying recently identified TRIM37 mutations, a 17q22 deletion of maternal origin combined with a TRIM37 variant of paternal origin. Here we found quantitative and functional defects in CD4+ T cells from this MUL case. Low levels of TRIM37 protein were specifically detected in CD4+ T cells of MUL patient and associated with their altered proliferation and cytokine production. Of note, both CD4+ and CD8+ T lymphocytes of MUL child displayed an effector memory phenotype compared with healthy children. This clinical case research highlighted the possible role of TRIM37 in the control of immune cell number and function, especially in CD4+ T cells. Finally, this study may contribute to the novel mechanistic studies aim of identifying, in depth, the role of the TRIM37 protein in the immune system.

Successful Total Pericardiectomy for Constrictive Pericarditis in the First Series of Japanese Patients With Mulibrey Nanism.

Patients with Mulibrey nanism (MUL) present with growth failure and multiple organ manifestations, and MUL is caused by mutations in TRIM37. In this article, we report on the first case series of Japanese patients with MUL who developed congestive heart failure due to constrictive pericarditis. Our case series suggests that early diagnosis and total pericardiectomy before adherence of the pericardium might provide clinical benefit and better prognosis for MUL.

Mulibrey nanism: Two novel mutations in a child identified by Array CGH and DNA sequencing.

In childhood, several rare genetic diseases have overlapping symptoms and signs, including those regarding growth alterations, thus the differential diagnosis is sometimes difficult. The proband, aged 3 years, was suspected to have Silver-Russel syndrome because of intrauterine growth retardation, postnatal growth retardation, typical facial dysmorphic features, macrocephaly, body asymmetry, and bilateral fifth finger clinodactyly. Other features were left atrial and ventricular enlargement and patent foramen ovale. Total X-ray skeleton showed hypoplasia of the twelfth rib bilaterally and of the coccyx, slender long bones with thick cortex, and narrow medullary channels. The genetic investigation did not confirm Silver-Russel syndrome. At the age of 5 the patient developed an additional sign: hepatomegaly. Array CGH revealed a 147 kb deletion (involving TRIM 37 and SKA2 genes) on one allele of chromosome 17, inherited from his mother. These results suggested Mulibrey nanism. The clinical features were found to fit this hypothesis. Sequencing of the TRIM 37 gene showed a single base change at a splicing locus, inherited from his father that provoked a truncated protein. The combined use of Array CGH and DNA sequencing confirmed diagnosis of Mulibrey nanism. The large deletion involving the SKA2 gene, along with the increased frequency of malignant tumours in mulibrey patients, suggests closed monitoring for cancer of our patient and his mother. Array CGH should be performed as first tier test in all infants with multiple anomalies. The clinician should reconsider the clinical features when the genetics suggests this. © 2016 Wiley Periodicals, Inc.

[Ascites in Mulibrey syndrome]. / Ascites u Mulibrev syndromu.

The authors describe a case of 22 years old adult male with Mulibrey syndrome. This is an autosomal recessive hereditary disease that manifests through multiple malformations. Diagnosis of Mulibrey syndrome in the present case was first based on clinical signs (facial dysmorphia, growth disorder, muscle hypotrophy) and was later confirmed by genetic examination. At the age of 18 months, the patient underwent surgery for Wilms' tumour followed by cytostatic therapy. Facial, neck and lower extremities oedemas started to occur from the age of 11 years when diastolic ventricular dysfunction was also diagnosed. Pericardiectomy was performed at the age of 13 with no significant clinical effect. Significant ascites dominated the clinical picture and required repeated paracentesis at the age of 15 years. Subjective complaints improved when adequate diuretic therapy was introduced and ascites was managed with conservative therapy without the need for further paracentesis.

A novel mutation in TRIM37 is associated with mulibrey nanism in a Turkish boy.

Mulibrey nanism is a rare autosomal-recessive disorder characterized by prenatal onset severe growth retardation and pericardial constriction associated with abnormalities of muscle, liver, brain and eye. More than 80% of previously reported patients are of Finnish origin in whom a founder mutation in the TRIM37 gene have been described. We report on a 7-year-old Turkish boy who presented with classical phenotypic features of mulibrey nanism. Mutation screening of the TRIM37 gene revealed that the proband had a homozygous two base pair deletion, c.1894_1895delGA, resulting in a frame-shift and a premature termination codon. Our proband is one of the rare examples of mulibrey nanism outside Finland and extends the mutation spectrum in this disorder.