A rare case of mosaic monosomy 21 in a Moroccan patient: clinical findings and insights from a systematic review

Abstract

INTRODUCTION AND OBJECTIVE: Complete monosomy 21 is a rare and lethal chromosomal disorder, with fewer than 50 cases reported. Its mosaic form is the only viable presentation, yet the full phenotypic spectrum remains poorly understood, prompting this work to expand clinical and cytogenetic insights. METHODS: We report the first genetically confirmed African case in a female infant referred for genetic testing because of distinctive dysmorphic features. Blood karyotype revealed 45,XX,-21[2]/46,XX[28] mosaicism, and fluorescence in-situ hybridization showed 15 and 25% mosaicism in blood and buccal cells, respectively. A systematic literature review identified 23 previously reported cases, including nine isolated and 14 with additional chromosomal abnormalities. RESULTS: The average maternal age was 27.5 years, unlike trisomy 21, where advanced maternal age is a major risk factor. Clinical manifestations include microcephaly, craniofacial dysmorphism, and congenital heart defects, with more severe phenotypes in complex cases. Hematological anomalies vary, with anemia in isolated and thrombocytopenia in complex cases. Notably, our patient displayed previously unreported peripheral hypothyroidism. The correlation between mosaicism levels and clinical severity remains unclear, highlighting the need for multi-tissue analyses. CONCLUSION: TThis study expands current knowledge of mosaic monosomy 21 and emphasizes the value of detailed cytogenetic assessment and phenotypic characterization to better define its clinical spectrum.