SA25 - AN INHERITED DISTAL 16P11.2 DELETION DEMONSTRATES VARIABLE EXPRESSIVITY AND INCOMPLETE PENETRANCE FOR PSYCHIATRIC ILLNESS AS WELL AS ASSOCIATION WITH RHIZOMELIC SHORTENING: A CASE REPORT

Abstract

Background The most commonly reported 16p Copy Number Variant (CNV) - 16p11.2 deletion syndrome (16pDS) (~600 kb; 29.5 -30.1 Mb) – has been robustly associated with schizophrenia (SZ), as well as Intellectual Disabilities (ID)/Developmental Delays (DD), congenital anomalies, dysmorphic features and obesity. Non-overlapping “distal” 16p11.2 deletions (~200 kb; 28.7 -28.9 Mb) are less commonly reported, but have a variable phenotype similar to that of 16pDS, including emerging data suggesting a psychiatric phenotype. We report here on a parent/child dyad who share a distal 16p11.2 deletion. Methods Patient 1 (index) was assessed (for indications including seizures, DD, and short limbs) at ages 2, 17, and 36, when she had clinical Chromosomal Microarray (CMA) (Affymetrix Cytoscan HD array, clinical thresholds: 200 kb (deletions), 400 kb (duplications), Chromosome Analysis suite (v2.0.0 195)). Fluorescence in Situ Hybridization (FISH) was used to confirm the deletion and determine origin. Results Patient 1 was born at term to non-consanguineous parents. A 46XX karyotype was confirmed at age 2 and 17 (testing indications: myoclonic seizures, DD, rhizomelic shortening of upper limbs). At age 17, she was also noted to have small hands ( Discussion While distal 16p11.2 deletions have been shown to increase risk for schizophrenia, this report contributes to the emerging evidence that this CNV is also associated with broader psychiatric phenotypes, such as bipolar disorder. The father's milder cognitive and metabolic phenotype supports variable expressivity of distal 16p11.2 deletions, even when inherited; his negative psychiatric history reinforces the incomplete penetrance of this CNV for psychiatric disorders. This report also contributes to the generation of a more thorough clinical description of the phenotypic range of distal 16p11.2 deletion, which we suggest, includes rhizomelic limb shortening.