A Case of Malan Syndrome With Pulmonary Artery Dilatation due to a Novel Frameshift Variant in Exon 2 of the NFIX Gene.

Malan syndrome is a rare overgrowth disorder caused by deletions or pathogenic variants in the NFIX gene. Here, we present the case of a Japanese male infant with Malan syndrome, which was caused by a novel frameshift variant resulting from an eight-base insertion in Exon 2 of the NFIX gene. Echocardiography revealed dilatation of the pulmonary artery without hemodynamic abnormalities. Malan syndrome shares many clinical features with Sotos syndrome, including overgrowth, macrocephaly, developmental delay, and intellectual disability. Therefore, molecular genetic testing is required for diagnosis. Pathogenic variants in the NFIX gene have also been reported in individuals with Marshall-Smith syndrome. Some individuals exhibit phenotypic overlap between Malan syndrome and Marshall-Smith syndrome. Our patient was diagnosed with Malan syndrome because he had a frameshift variant in Exon 2, resulting in haploinsufficiency, and exhibited macrocephaly, but not proptosis or micrognathia. To our knowledge, this is the second reported case in the literature of concomitant pulmonary artery dilatation in Malan syndrome.