Clinical characterization of individuals with the distal 1q21.1 microdeletion is described in this summary.
Deletions of the 1q21.1 segment may be subdivided into two groups: proximal (located in the interval of 144.9-146.2 Mb) and distal (~146.4-148.8 Mb). Proximal del 1q21.1 in the presence of modifying variant in RBM8A leads to TAR syndrome (thrombocytopenia-absent radius). Clinical consequences of the distal del 1q21.1 are not so clear.
The authors analyzed manifestations in a large cohort of patients with this deletion obtained from their own practice (34) and 13 patients from the Brunetti-Pierri et al. study. In total 43 out of 47 patients had “pure” deletions of the distal segment of 1q21.1 (BP3-BP4). Four others also included deletions of the more proximal area (BP2-BP4). Cases from prenatal diagnosis were not included. In 24 patients, parental specimens were not available. In 15 out of 23 patients where parental specimens were available, deletion was inherited from one of the parents.
The most common manifestation was intellectual disability, reported in ~3/4 of patients. Psychiatric and behavioral abnormalities were found in 22 patients, with attention deficit hyperactivity disorder the most commonly reported (10 out of 22). Autism was diagnosed in 6 patients. Microcephaly was recorded in 22/43 examined patients. 14 out of 47 had seizures. Hearing loss was reported in 6 patients. 30 out of 47 revealed mild dysmorphic features, but there was no specific type of dysmorphism allowing clinical recognition of distal del 1q21.1. Structural defects of internal organs were relatively uncommon. Congenital heart defects were diagnosed in 9 patients, and congenital kidney defects in 4, although not every patient had sufficient examination regarding these systems. Short stature was reported in 15 out of 36 patients.
Significant variability may be explained at least partially by the presence of additional copy number variants or mutations in the genes within the complementary segment on the non-deleted chromosome. It should be noted that this review included only symptomatic individuals and did not include information on mildly affected (or healthy) parents of the affected individuals.
Edwards S.D. et al. “Clinical characterization of individuals with the distal 1q21.1 microdeletion”. “Amer. J. Med. Genet.” 2021, v. 185 (5), 1388-1398.
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