Co-occurrence of Mulibrey Nanism and Jacobs Syndrome in a Pediatric Patient: Importance of Comprehensive Genetic Testing
Pritti Kumari *
Genetics Division, Department of Obstetrics and Gynecology, Institute of Kidney Diseases and Research Centre, Dr. HL Trivedi Institute of Transplantation Sciences (IKDRC-ITS), Civil Hospital Campus, Asarwa, Ahmedabad 380016, India.
Rohina Aggarwal
Department of Obstetrics and Gynecology, Institute of Kidney Diseases and Research Centre, Dr. HL Trivedi Institute of Transplantation Sciences (IKDRC-ITS), Ahmedabad, India.
Akshi Valodara
Genetics Division, Department of Obstetrics and Gynecology, Institute of Kidney Diseases and Research Centre, Dr. HL Trivedi Institute of Transplantation Sciences (IKDRC-ITS), Civil Hospital Campus, Asarwa, Ahmedabad 380016, India.
Hetvi Patel
Genetics Division, Department of Obstetrics and Gynecology, Institute of Kidney Diseases and Research Centre, Dr. HL Trivedi Institute of Transplantation Sciences (IKDRC-ITS), Civil Hospital Campus, Asarwa, Ahmedabad 380016, India.
Dipak Dhoriya
Genetics Division, Department of Obstetrics and Gynecology, Institute of Kidney Diseases and Research Centre, Dr. HL Trivedi Institute of Transplantation Sciences (IKDRC-ITS), Civil Hospital Campus, Asarwa, Ahmedabad 380016, India.
Ankita Suthar
Genetics Division, Department of Obstetrics and Gynecology, Institute of Kidney Diseases and Research Centre, Dr. HL Trivedi Institute of Transplantation Sciences (IKDRC-ITS), Civil Hospital Campus, Asarwa, Ahmedabad 380016, India.
Somesh Aggarwal
Department of Opthalmology, M & J Regional Institute of Ophthalmology, Ahmedabad, India.
*Author to whom correspondence should be addressed.
Abstract
Background: Mulibrey Nanism (Muscle-liver-brain-eye Nanism; MUL) is a rare autosomal recessive disorder caused by pathogenic variants in the TRIM37 gene. It is characterised by postnatal growth retardation, craniofacial dysmorphism, organ involvement including hepatomegaly and cardiomyopathy, and predisposition to tumours. Jacobs Syndrome (47, XYY) is a sex chromosome aneuploidy that may present with tall stature, behavioural issues, or be asymptomatic. Co-occurrence of these two conditions is extremely rare and poses diagnostic challenges.
Case Description: A 6-year-old boy was referred for genetic evaluation due to clinical features resembling Silver-Russell syndrome. Detailed genetic investigation was undertaken using a combination of classical and advanced techniques. Cytogenetic analysis with G-banding revealed a mosaic karyotype: 47, XYY[25]/46, XY[25], diagnostic of Jacobs Syndrome. Chromosomal microarray (CMA) confirmed a mosaic gain of the Y chromosome and showed no additional pathogenic copy number variations. Whole exome sequencing (WES) identified a homozygous nonsense variant c.586C>T in the TRIM37 gene, confirming the diagnosis of Mulibrey Nanism.
Conclusion: Accurate diagnosis of syndromic presentations requires a stepwise approach and the use of multiple genetic modalities. This case exemplifies the value of exhaustive testing in unravelling rare genetic overlaps and guiding appropriate clinical management.
Keywords: Mulibrey, Jacobs syndrome, whole exome sequencing, karyotype, Silver-Russel syndrome, growth restriction