A Germline Mutation in the C2 Domain of PLCγ2 Associated with Gain-of-Function Expands the Phenotype for PLCG2-Related Diseases.

We report three new cases of a germline heterozygous gain-of-function missense (p.(Met1141Lys)) mutation in the C2 domain of phospholipase C gamma 2 (PLCG2) associated with symptoms consistent with previously described auto-inflammation and phospholipase Cγ2 (PLCγ2)-associated antibody deficiency and immune dysregulation (APLAID) syndrome and pediatric common variable immunodeficiency (CVID). Functional evaluation showed platelet hyper-reactivity, increased B cell receptor-triggered calcium influx and ERK phosphorylation. Expression of the altered p.(Met1141Lys) variant in a PLCγ2-knockout DT40 cell line showed clearly enhanced BCR-triggered influx of external calcium when compared to control-transfected cells. Our results further expand the molecular basis of pediatric CVID and phenotypic spectrum of PLCγ2-related defects.

Infantile Hemangioma of the Breast: Long-Term Assessment of Outcomes.

Background: The literature is meager regarding the natural history and outcomes of infantile hemangiomas (IHs) in the breast. Treatment in childhood may be considered due to psychosocial and physical concerns with breast development. Early surgical intervention may cause iatrogenic breast asymmetry and possibly impair lactation later in life. This study characterizes the clinical presentation, management, and long-term outcomes of IHs arising in the breast. Methods: Female patients aged 11 years or older at presentation were included in a retrospective review of the Vascular Anomalies Center database for patients with IHs of the breast seen at our institution between 1980 and 2020. Breast development was ascertained by a structured telephone interview, physical examination, or photographs. Results: A total of 10 patients met criteria for inclusion in this study. The median age at enrollment was 14 years (11-36 years). Breast asymmetry was noted in 60% of patients (n = 6). Of the four patients who underwent subtotal excision of breast IH, three developed ipsilateral breast hypoplasia. Breast asymmetry was also noted in three of five patients who did not receive medical treatment: two with hypoplasia and one with hyperplasia. No asymmetry was noted in the single patient who received corticosteroid. Conclusions: IHs involving the nipple-areola complex can be associated with breast asymmetry. Hypoplasia was noted in patients not treated with corticosteroid or resection in childhood. These findings suggest that systemic treatment should be considered. Longitudinal follow-up on patients treated with propranolol will elucidate its possible benefits in minimizing breast asymmetry.