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Overlap between EEC and AEC syndrome and immunodeficiency in a preterm infant with a TP63 variant
Kjell Helenius1, Liisa Ojala2, Leena Kainulainen1
1Department of Paediatrics and Adolescent Medicine, Turku University Hospital and University of Turku, Turku, Finland.
Insights
TP63 gene variants cause overlapping syndromes like EEC and AEC. This case highlights a novel cardiac finding and immune deficiency in a patient with TP63-related disorders, emphasizing complex care needs.
Area of Science:
- Genetics
- Developmental Biology
- Clinical Medicine
Background:
- Pathogenic variants in the TP63 gene are associated with a spectrum of developmental disorders, including ectrodactyly-ectodermal dysplasia-clefting (EEC) syndrome and ankyloblepharon-ectodermal dysplasia-clefting (AEC) syndrome.
- Historically, TP63-related phenotypes have been classified into distinct syndromes based on clinical presentation and variant location, though significant overlap exists.
- Understanding the genotype-phenotype correlations in TP63-related disorders is crucial for accurate diagnosis and management.
Observation:
- We report a patient presenting with overlapping features of EEC and AEC syndromes, including cleft lip and palate, split feet, ectropion, and skin/corneal erosions.
- The patient harbors a de novo heterozygous pathogenic variant, c.1681T>C, p.(Cys561Arg), in exon 13 of the TP63 gene.
- Novel findings in this patient include cardiac compartment enlargement with secondary mitral insufficiency and a rare occurrence of immune deficiency.
Findings:
- The identified TP63 variant (c.1681T>C, p.(Cys561Arg)) is associated with a complex phenotype that bridges distinct previously defined syndromes.
- The co-occurrence of cardiac abnormalities and immune deficiency expands the known clinical spectrum of TP63-related disorders.
- Prematurity and very low birth weight further complicated the clinical course and management.
Implications:
- This case underscores the phenotypic variability and significant overlap in TP63-related disorders, challenging traditional syndrome classifications.
- The novel cardiac and immune findings necessitate a broader diagnostic consideration for TP63 variants.
- Effective management requires a multidisciplinary approach to address the diverse and complex clinical manifestations, including potential long-term cardiac and immunological surveillance.
Abstract:
Pathogenic variants in the transcription factor TP63 gene cause a variety of clinical phenotypes, such as ectrodactyly-ectodermal dysplasia-clefting (EEC) syndrome and ankyloblepharon-ectodermal dysplasia-clefting (AEC) syndrome. Historically, TP63-related phenotypes have been divided into several syndromes based on both the clinical presentation and location of the pathogenic variant on the TP63 gene. This division is complicated by significant overlap between syndromes. Here we describe a patient with clinical characteristics of different TP63-associated syndromes (cleft lip and palate, split feet, ectropion, erosions of the skin and corneas), associated with a de novo heterozygous pathogenic variant c.1681 T>C, p.(Cys561Arg) in exon 13 of the TP63 gene. Our patient also developed enlargement of the left-sided cardiac compartments and secondary mitral insufficiency, which is a novel finding, and immune deficiency, which has only rarely been reported. The clinical course was further complicated by prematurity and very low birth weight. We illustrate the overlapping features of EEC and AEC syndrome and multidisciplinary care needed to address the various clinical challenges.
