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Mafalda S. Melo1; Susana L. Ferreira1; Sofia Nunes1; Maria Sacras2; Fátima Abreu3; Tiago Rito4; Salomé Almeida5; Teresa Kay1; Diana Antunes1

1 - Serviço de Genética Médica, Área de Pediatria, Hospital Dona Estefânia, Centro Hospitalar e Universitário de Lisboa Central, Lisboa;
2 - Serviço de Cirurgia Pediátrica, Hospital Dona Estefânia, Centro Hospitalar e Universitário de Lisboa Central, Lisboa;
3 - Unidade de Pneumologia Pediátrica, Hospital Dona Estefânia, Centro Hospitalar e Universitário de Lisboa Central, Lisboa;
4 - Serviço de Cardiologia Pediátrica, Hospital Santa Marta, Centro Hospitalar e Universitário de Lisboa Central, Lisboa;
5 - Centro de Investigação, Centro Hospitalar e Universitário de Lisboa Central, Lisboa

24th Annual Meeting, Sociedade Portuguesa de Genética Humana, virtual meeting, 20 de Novembro. Sob a forma de poster

Background: Autosomal recessive cutis laxa type 1C (ARCL1C, MIM #613177) is a rare connective tissue disorder caused by LTBP4 mutations. ARCL1C presents with cutis laxa, early childhood-onset pulmonary emphysema, peripheral pulmonar artery stenosis, and other evidence of a generalized connective disorder such as hernias. To date, only 19 patients have been reported.
Case report: A 4-month-old boy was referred to our clinic for multiple congenital anomalies evaluation. He was the child of a consanguineous and healthy Cape Verdean couple. Clinical history included neonatal hypotonia, congenital heart disease characterized by moderate peripheral pulmonary artery stenosis, ostium secundum atrial septal defect and mild aortic valve insufficiency, diaphragmatic hernia, and inguinal hernia. At our observation, he had loose skin with sagging cheeks, sloping forehead, periorbital fullness, depressed nasal bridge with anteverted nares, everted lower lip and micrognathia. A clinical diagnosis of cutis laxa was given due to the presence of the dermatological hallmark. WES-based virtual panel revealed a homozygous splice site variant in LTBP4 gene [NM_003573.2:c.780+2T>G p.?], classified as pathogenic, establishing the diagnosis of ARCL1C. This specific variant was only reported in one case. The case was a Cape Verdean girl who had a similar presentation and died by the age of two due to pulmonary emphysema. Up to the moment, our patient did not show signs of respiratory distress. However, multidisciplinary evaluations are planned including periodic assessment of pulmonary function and imaging of gastrointestinal and urinary tracts. Also, the patient developed neck abscesses, which we hypothesized it could be a new ARCL1C feature.
Conclusion: Data from patients are needed to better characterize the LTBP4-related phenotype and define clinical diagnostic criteria, genotype-phenotype correlations, and prognosis. By reporting cervical abscesses as a possible additional feature related to LTBP4 mutations, this case further broadens the clinical spectrum of ARCL1C. Additionally, it enabled na appropriate surveillance and genetic counselling to the patient and family.

Palavras Chave: ARCL1C, Cutis laxa, gene LTBP4, multiple congenital anomalies