10q22.3q23.2 recurrent region (includes BMPR1A)

Lecoquierre et al. (2020) reported a novel case and reviewed the literature of 15 prior families and 20 DECIPHER database patients (12 with phenotypic information) with the recurrent 10q22.3q23.2 deletion. Consistent reported features amongst these individuals included developmental delay/intellectual disability, delayed language, behavioral abnormalities, heart defects, and dysmorphic features. Of the novel and previously published cases, inheritance was de novo for most (10/16), familial (dominant) in 1, maternal in 1, and unknown for 4 patients. The case report involving a 25-year-old adult patient was notable for the presence of BMPR1A-associated tumors, severe juvenile polyposis syndrome and gastric adenocarcinoma, as this phenotype was not previously reported in patients with deletions isolated to the recurrent 10q22.3q23.2 region (i.e. excluding co-deletion of the gene PTEN, which resides outside of and distal to LCR-4). Due to the early age of ascertainment for most previously reported 10q22.3q23.2 recurrent deletion patients (11 patients ascertained at <5 years of age), the authors noted the absence of these reported phenotypes, JPS and/or GI tract adenocarcinomas, may not preclude a risk for development in young adulthood, and recommended early surveillance for these tumors.

Petrova et al. (2014) reported a novel case and reviewed the literature of 13 prior patients with recurrent 10q22.3q23.2 deletions. Clinical findings in common across these 14 patients typically included developmental delay (particularly in speech) and craniofacial dysmorphisms (particularly hypertelorism, up- or downslanting palpebral fissures and flat nasal bridge), and variably included palatal anomalies, congenital heart defects, and club foot. Inheritance was de novo for most (11/14), maternal for 2 and unknown for 1 patient. The authors noted none of these patients had juvenile polyposis syndrome (JPS) which was thought to require co-deletion of BMPR1A, which resides within the recurrent region, and PTEN, which is just outside of (distal to) LCR-4, although 11/14 were age 5 years or younger at the time of ascertainment.

Molck et al. (2017) reported a novel case and summarized clinical findings of 14 prior patients from the literature with 10q22.3q23.2 deletions. Their proband was also found to carry a 189 kb deletion within 16q12.1, which the authors noted could not be excluded as contributing to their phenotype, though reported features overlapped those of previously reported patients.

van Bon et al. (2011) summarized clinical findings for 5 patients with recurrent 10q22.3q23.2 deletions and 1 patient with a unique overlapping deletion identified by routine clinical microarray testing. Common phenotypic features among these 5 patients included developmental delay, speech delay, and dysmorphic features (such as hypertelorism and low-set ears). Additional variable findings included cardiac anomalies, brain anomalies, hand abnormalities and congenital breast aplasia. One patient had an additional de novo duplication in 2q36 (significance not disclosed) and another patient had a 47,XYY karyotype. The 10q22.3q23.3 deletion was apparently de novo in 3/5 cases, inherited from a mother who underwent special schooling in one case, and of unknown inheritance in the last case.

Fernandez-Rozadilla et al. (2012) performed a search for rare copy number variants detected by microarray analysis in a cohort of 32 patients with familial colorectal cancer type X, juvenile polyposis, or hereditary mixed polyposis syndromes. The recurrent 10q22.3q23.2 deletion was reported in a patient with a history of mild intellectual disability, an unspecified heart condition, and apparently sporadic synchronous colorectal adenocarcinomas at age 49 years. The family history was negative for colorectal cancer.