19q13.32 microdeletion syndrome: three new cases.

Area of Science:

• Genetics
• Developmental Biology
• Clinical Medicine

Background:

• A previous report identified a 732 kb 19q13.32 microdeletion associated with a distinct phenotype.
• This phenotype included intellectual disability, facial asymmetry, ptosis, oculomotor abnormalities, orofacial clefts, cardiac defects, scoliosis, and chronic constipation.

Observation:

• Three unrelated patients with developmental delay and dysmorphic features were found to have interstitial 19q13.32 microdeletions of varying sizes.
• Patient 1 presented with a 1.3 Mb deletion and exhibited hypotonia, aplasia of the posterior corpus callosum, bilateral ptosis, oculomotor paralysis, facial asymmetry, submucosal cleft palate, micrognathia, aortic arch abnormalities, hypospadias, and colonic atony.

Findings:

• The study defines a recognizable 19q13.32 microdeletion syndrome characterized by facial asymmetry, ptosis, oculomotor paralysis, orofacial clefting, micrognathia, kyphoscoliosis, aortic defects, and colonic atony.
• Candidate genes (e.g., NPAS1, NAPA, ARHGAP35, SLC8A2, DHX34, MEIS3, ZNF541) within the deleted region are implicated in the observed phenotype.
• These genes are expressed in key developmental tissues, including the brain, heart, gastrointestinal tract, and musculoskeletal system.

Implications:

• This research expands the understanding of the phenotypic spectrum associated with 19q13.32 microdeletions.
• It highlights the role of haploinsufficiency of specific genes in this region in causing complex developmental disorders.
• The findings aid in the clinical recognition and genetic counseling for individuals with 19q13.32 deletions.