De novo MYH9 mutation in congenital scalp hemangioma

Abstract

Congenital hemangiomas are tumor-like vascular malformations with poorly understood pathogenesis. We report the case of a neonate with a massive congenital scalp hemangioma that required urgent neurosurgical removal on the second day of life because of concern for high-flow arteriovenous shunting. Exome sequencing identified a rare damaging de novo germline mutation in MYH9 (c.5308C>T, p.[Arg1770Cys]), encoding the MYH9 nonmuscle myosin IIA. MYH9 has a probability of loss-of-function intolerance (pLI) score of >0.99 and is highly intolerant to missense variation (z score = 5.59). The p.(Arg1770Cys) mutation substitutes an evolutionarily conserved amino acid in the protein's critical myosin tail domain and is predicted to be highly deleterious by SIFT, PolyPhen-2, MetaSVM, and CADD. MYH9 is a known regulator of cytokinesis, VEGF-regulated angiogenesis, and p53-dependent tumorigenesis. These findings reveal a novel association of germline de novo MYH9 mutation with congenital hemangioma.

Preterm neonate with a large congenital hemangioma on maxillofacial site causing thrombocytopenia and heart failure: A case report

“…It is reported that NICH can be treated with propranolol alone with no significant side effects[ 2 ]; however, conservative treatment did not work for our patient[ 1 ].…”

“…Hemangiomas occurring in the neonatal period are typically benign and the underlying pathogenetic mechanisms are not well characterized[ 1 ]. Congenital hemangiomas (CHs) are uncommon entities[ 2 ] accounting for < 3% of all hemangiomas. CHs have a predilection for occurring in the cranio-maxillo-facial region and lower limbs, while suboccipital neck, elbow, and knees are the other reported sites of occurrence[ 3 ].…”

Infantile Scalp Hemangiomas: Surgical Management and Lessons Learned

“…Review of the literature revealed 19 previously published case studies (from 1981 to 2022) of pediatric scalp hemangiomas undergoing excision (Supplemental Table 1, Supplemental Digital Content 1, http://links.lww.com/SCS/F594). [8][9][10][11][12][13][14][15][16][17][18] Of the patients whose sex was reported, the majority (78%) were female (F:M ratio of 3.5). Patient age at the time of excision ranged from 2 days old to 14 years old, with a median age of 16 weeks.…”

“…Excluding outliers (14-year-old), the average and SD of surgical age were 24 and 31 weeks, respectively. The anatomic location of the scalp lesions had the following distribution: 32% temporal (including mastoid and postauricular), 9,11,15 21% parietal, 13,14,16,18 21% frontal, 8,11,13,17 11% temporoparietal, 10,12 5% occipitoparietal, 12 5% frontoparietal, 12 and 5% on the vertex of the scalp. 11 The hemangiomas ranged in size from 0.5 × 2 × 1.5 cm 16 to 14 × 10 cm.…”

MYH9-related disease: it does exist, may be more frequent than you think and requires specific therapy

“…Additionally, MYH9 is considered a tumour suppressor, and whether the incidence or severity of malignancy differs in patients with germline mutations requires further studies [2]. Congenital haemangioma [20], the MYH9-associated elastin aggregation (MALTA) syndrome characterized by sweat duct proliferations and irregular elastin aggregations [21], and non-syndromic orofacial cleft in Taiwanese patients [22] have also been associated to MYH9 mutations, but not necessarily with MATINS.…”