Clinical and genetic evaluation of six children with diffuse capillary malformation and undergrowth

Cubiró, Xavier; Rozas‐Muñoz, Eduardo; Castel, Pau; Crespo, Esther Roè; Garcia‐Melendo, Cristina; Puig, L.; Baselga, Eulàlia

doi:10.1111/pde.14252

Cited by 9 publications

(11 citation statements)

References 21 publications

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“…Somatic pathogenic variants associated with undergrowth in vascular lesions have been previously reported in PIK3CA, TEK, GNAQ, and GNA11 (Martinez-Glez et al, 2022). The association of mosaic variants in PIK3CA with capillary malformations with undergrowth was confirmed by another group (Cubir o et al, 2020).…”

Section: Introductionmentioning

confidence: 64%

“…Pathogenic variants in several genes have been implicated in CM with undergrowth. Undergrowth with vascular lesions was observed in patients who had somatic pathogenic variants in PIK3CA , TEK , GNAQ , and GNA11 (Cubiró et al, 2020; Martinez‐Glez et al, 2022). Interestingly, somatic pathogenic variants in PIK3CA more commonly cause overgrowth (Cubiró et al, 2020; Lee et al, 2013).…”

Section: Discussionmentioning

confidence: 99%

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Mosaic pathogenic variants in AKT3 cause capillary malformation and undergrowth

Bolli

Nriagu

Britt

et al. 2023

American J of Med Genetics Pt A

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Capillary malformations are slow‐flow vascular malformations that affect the microcirculation including capillaries and post capillary venules and can be associated with growth differences. Specifically, the association of capillary malformations with undergrowth is a vastly understudied vascular syndrome with few reports of genetic causes including PIK3CA, GNAQ, and GNA11. Recently, a somatic pathogenic variant in AKT3 was identified in one child with a cutaneous vascular syndrome similar to cutis marmorata telangiectatica congenita, undergrowth, and no neurodevelopmental features. Here, we present a male patient with a capillary malformation and undergrowth due to a somatic pathogenic variant in AKT3 to confirm this association. It is essential to consider that mosaic pathogenic variants in AKT3 can cause a wide spectrum of disease. There is a need for future studies focusing on capillary malformations with undergrowth to understand the underlying mechanism.

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Section: Introductionmentioning

confidence: 64%

Section: Discussionmentioning

confidence: 99%

Mosaic pathogenic variants in AKT3 cause capillary malformation and undergrowth

Bolli

Nriagu

Britt

et al. 2023

American J of Med Genetics Pt A

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“…Other than hearing loss, the patients reported here had no additional clinical characteristics reported to be associated with the GRHL2 genetic defect, such as diffuse capillary malformations and undergrowth [29], ectodermal dysplasia [9], or eye abnormalities [28]. Recent studies have also demonstrated the role of the GRHL family of proteins in carcinogenesis, as reviewed in [32,33], specifically GRHL2 in human breast cancer [34].…”

Section: Discussionmentioning

confidence: 79%

“…GRHL2 is a transcriptional factor [5], so those domains are crucial for its function. The majority of hearing-loss-related variants are truncating variants, while missense and deep intronic variants seem to be more likely to be associated with other GRHL2-related pathologies [9,10,[28][29][30]. In zebrafish, loss of GRHL2b induces midbrain-hindbrain boundary and otic vesicle defects [31].…”

Section: Discussionmentioning

confidence: 99%

Novel GRHL2 Gene Variant Associated with Hearing Loss: A Case Report and Review of the Literature

Podkrajšek

Tesovnik

Urbančič

et al. 2021

Genes

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In contrast to the recessive form, hearing loss inherited in a dominant manner is more often post-lingual and typically results in a progressive sensorineural hearing loss with variable severity and late onset. Variants in the GRHL2 gene are an extremely rare cause of dominantly inherited hearing loss. Genetic testing is a crucial part of the identification of the etiology of hearing loss in individual patients, especially when performed with next-generation sequencing, enabling simultaneous analysis of numerous genes, including those rarely associated with hearing loss. We aimed to evaluate the genetic etiology of hearing loss in a family with moderate late-onset hearing loss using next-generation sequencing and to conduct a review of reported variants in the GRHL2 gene. We identified a novel disease-causing variant in the GRHL2 gene (NM_024915: c.1510C>T; p.Arg504Ter) in both affected members of the family. They both presented with moderate late-onset hearing loss with no additional clinical characteristics. Reviewing known GRHL2 variants associated with hearing loss, we can conclude that they are more likely to be truncating variants, while the associated onset of hearing loss is variable.

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“…There are just a few single reported patients, including a previous description of the patient MV00880 17 and small series 18 Combining the type of vascular malformation with molecular defects we identified in our cohort three different groups: undergrowth associated with (1) a capillary malformation (8.1%), ( 2) venous (32.4%), or combined venous-capillary malformation (36.8%), and…”

Section: Discussionmentioning

confidence: 80%

Segmental undergrowth is associated with pathogenic variants in vascular malformation genes: A retrospective case‐series study

et al. 2021

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Segmental overgrowth has been widely described in patients with congenital vascular anomalies. However, segmental undergrowth has been poorly characterized, and no large series of patients have been published. We present the clinical and molecular characteristics a cohort of 37 patients with vascular malformations and segmental undergrowth. True undergrowth was only considered when the musculoskeletal system was involved to avoid confusion with other causes of segmental reduction, as in lipodystrophy or the long-term osteopenia seen in patients with Servelle-Martorell syndrome. Deep high-throughput sequencing was performed in tissue samples from 20 patients using a custom panel. We identified three groups: undergrowth associated with (1) venous, (2) capillary-venous, and (3) lymphatic-capillary-venous malformations. Congenital or early childhood onset undergrowth can occur with or without associated overgrowth. Different likely pathogenic or pathogenic variants were detected in 13 of 20 (65%) tissue samples in the PIK3CA, TEK, GNAQ, or GNA11 genes. In conclusion, the eponymous Servelle-Martorell syndrome should not be used as a synonym for undergrowth. Segmental undergrowth should be considered a characteristic associated with vascular malformations. Patients with PIK3CA variants show all different combinations of overgrowth and undergrowth. Thus, the term PROS (PIK3CA-related overgrowth spectrum) does not cover the entire spectrum.

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Clinical and genetic evaluation of six children with diffuse capillary malformation and undergrowth

Cited by 9 publications

References 21 publications

Mosaic pathogenic variants in AKT3 cause capillary malformation and undergrowth

Mosaic pathogenic variants in AKT3 cause capillary malformation and undergrowth

Novel GRHL2 Gene Variant Associated with Hearing Loss: A Case Report and Review of the Literature

Segmental undergrowth is associated with pathogenic variants in vascular malformation genes: A retrospective case‐series study

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