A pure de novo 16p13.3 duplication and amplification in a patient with femoral hypoplasia, psychomotor retardation, heart defect, and facial dysmorphism—a case report and literature review of the partial 16p13.3 trisomy syndrome

Partial 16p trisomy syndrome is a rare disorder typically characterized by psychomotor retardation, prenatal and postnatal growth deficiency, cleft palate, and facial dysmorphism, with some patients also presenting with heart defects and urogenital anomalies. Pure 16p13.3 duplications usually occur de novo, while those duplications that associate with partial monosomy result rather from parental chromosomal translocations. Due to the large size of the aberrations, the majority of patients are identified by standard chromosome analysis. In all published cases, the minimal-causative duplicated region encompasses the CREBBP gene. Here, we report on the patient presenting with psychomotor retardation, femoral hypoplasia, and some features of the partial 16p trisomy syndrome, who carries a complex de novo terminal 16p13.3 microduplication with an overlapping region of amplification without translocation or associated monosomy. In contrast to the previously reported cases, the duplicated region of the patient does not involve CREBBP and other neighboring genes; still, the observed pattern of dysmorphic features of the index is characteristic of the described syndrome. Based on the animal studies and other published cases, we discuss the possible role of the PDK1 and IGFALS genes in the development of limb anomalies, while IFT140 could contribute both to the observed femoral phenotype and heart abnormalities in the patient. To the best of our knowledge, we present a proband harboring the smallest terminal 16p13.3 duplication of the size below 3 Mb. Therefore, our proband with her detailed phenotypic description may be helpful for clinicians who consult patients with this syndrome. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s13353-022-00743-7.