Single dominant lesion in capillary malformation-arteriovenous malformation (CM-AVM) RASA1 syndrome.

We report two cases with localized vascular malformations clinically resembling the "dominant lesion" seen in capillary malformation-arteriovenous malformation (CM-AVM) syndrome, however, lacking germline RASA1 variants but presenting double somatic RASA1 variants in affected tissue. Both patients presented with localized and superficial high-flow vascular malformations were treated with surgery and laser therapy and showed partial resolution. The study underscores the rarity of somatic RASA1 variants, contributes to understanding the "second-hit" pathophysiology in vascular lesions, and emphasizes the significance of clinical distinctions and genotyping for accurate diagnoses, offering implications for diagnosis, prognosis, and genetic counseling.

5q14.3 Microdeletion Syndrome With Simultaneous Involvement of MEF2C and RASA1. Clinical Case and Review of the Literature.

5q14.3 microdeletion syndrome is a rare condition involving multiple genes such as MEF2C and RASA1 and is potentially classified as a neurocutaneous syndrome. Deletion of the MEF2C gene accounts for the majority of clinical manifestations, including global developmental delay, intellectual disability, seizures, and behavioral disorders. RASA1 deletion is linked to capillary malformations with arteriovenous malformations (CM-AVM). Until now, only 17 cases have been described with deletions of both genes. We present the first case described in Spain with the microdeletion in the 5q14.3 cytoband simultaneously affecting both MEF2C and RASA1, exhibiting the typical manifestations of this entity, and review the published cases to date.

5q14.3 deletion neurocutaneous syndrome: Contiguous gene syndrome caused by simultaneous deletion of RASA1 and MEF2C: A progressive disease.

We report the case of a young girl who was presented with complex clinical symptoms caused by the deletion of contiguous genes: RASA1 and MEF2C, located on chromosome 5q14.3. Specifically, the diagnosis of her skin disorder and vascular malformations involving central nervous system is consistent with a RASopathy. The child's neurological manifestations are observed in most patients suffering from 5q14.3 by deletion or mutation of the MEF2C gene. A review of the literature allowed us to conclude that the contiguous deletion of genes RASA1 and MEF2C fulfills the criteria for the diagnosis of a Neurocutaneous syndrome as proposed by Carr et al. [2011]. We also assessed the penetrance of RASA1 and clinical manifestations of MEF2C according to the type of deletion. This child described presents the complete symptomatology of both deleted genes. We would also like to highlight the progression of the disorder.

Heredity of port-wine stains: investigation of families without a RASA1 mutation.

BACKGROUND: The prevalence of capillary malformations, also known as port-wine stains (PWS), is 0.3%. Familial segregation can occur. The capillary malformation-arteriovenous malformation (CM-AVM) phenotype is caused by mutations in the RASA1 gene. In PWS familial cases, the inheritance is considered to be autosomal dominant with variable penetrance. OBJECTIVE: Investigation of the heredity of PWS among patients who attended the vascular anomaly section at the Department of Dermatology in Malmoe, Southern Sweden, between 1993 and 2004 and to study the involvement of the RASA1 gene in patients with a positive family history of PWS. SUBJECTS AND METHODS: A total of 254 patients were examined and given a questionnaire regarding family history of PWS. The first group of 175 patients (109 females and 66 males) reported a negative family history. The other group of 65 patients (46 females and 19 males) reported a positive family history (50% parents or brothers and sisters). RESULTS: The heredity of PWS was 27% (65/240). Twenty-one patients with a positive family history and relatives had no CM-AVM phenotype for mutations in the RASA1 gene. CONCLUSION: PWS may have a stronger heredity component than it was reported earlier and inheritance should be considered when counseling a patient. RASA1 mutations do not explain the PWS in our patients.

Capillary Malformation-Arteriovenous Malformation Syndrome.

Capillary malformation-arteriovenous malformation (CM-AVM) is an autosomal dominant inherited rare type of vascular malformation encountered in a neonate and first described in 2003. It has been reported in association with heterozygous mutations in the RASA1 gene, which encodes the protein RASp21. In 2010, a German doctor proposed rhodoid nevus as a name for this type of capillary malformation; in ancient Greek, rhodoides means "rose-like" or "rose-colored." Accordingly, CM-AVM could also be called "rhodoid nevus syndrome." We report this case as its very challenging diagnosis with its further differentials and its association with thrombocytopenia.