CASE REPORT
Diagnostic and clinical approach to a paediatric patient with skin aplasia of the head as a rare manifestation of Xia-Gibbs syndrome caused by a new, potentially pathogenic de novo mutation in the AHDC1 gene
1
Medical University of Lublin, Lublin, Poland
Submission date: 2024-06-26
Final revision date: 2024-09-03
Acceptance date: 2024-10-19
Publication date: 2025-03-27
Pediatr Pol 2025;61(1):86-91
KEYWORDS
TOPICS
ABSTRACT
Xia-Gibbs syndrome is caused by pathogenic variants in the AHDC1 gene. The characteristic features of the syndrome include delayed psychomotor and speech development, short stature, hypotonia, intellectual disability, structural brain anomalies, and mild facial dysmorphia. A boy came to the Genetic Outpatient Clinic due to skin aplasia of the head, facial dysmorphic changes, syndactyly of the second and third toes, delayed motor development, squamous haemangiomas on the head and face, hypoplasia of tooth enamel, excessively developed subcutaneous tissue, hypotonia, and joint laxity. In next-generation whole-exome sequencing a potentially pathogenic variant c.1913G>A, p.Trp638Ter was detected in a single allele of the AHDC1, resulting in premature termination of the protein. The boy’s parents were not carriers of the lesion. Aplasia of the head’s skin is an extremely rare discovery in the phenotype of patients with Xia-Gibbs syndrome. Next-generation sequencing allowed for an accurate diagnosis and detection of a mutation in the AHDC1 gene.
REFERENCES (30)
1.
Online Mendelian Inheritance in Man, OMIM®. Johns Hopkins University, Baltimore, MD. MIM Number: 615829: 12 August 2020. Available from: : https://omim.org/ (accessed: 17.03.2024).
2.
Orphanet: an online database of rare diseases and orphan drugs. Copyright, INSERM 1997. Available from: https://www.orpha.net/consor/c... (accessed: 17.03.2024).
3.
Xia F, Bainbridge MN, Tan TY, et al. De novo truncating mutations in AHDC1 in individuals with syndromic expressive language delay, hypotonia, and sleep apnea. Am J Hum Genet 2014; 94: 784-789.
4.
Ritter AL, McDougall C, Skraban C, et al. Variable clinical manifestations of Xia-Gibbs syndrome: findings of consecutively identified cases at a single children’s hospital. Am J Med Genet A 2018; 176: 1890-1896.
5.
Baga M, Ivanovski I, Contrò G, et al. Novel insights from clinical practice: Xia-Gibbs syndrome with pes cavus, conjunctival melanosis, and eye asymmetry due to a de novo AHDC1 gene variant – a case report and a brief review of the literature. Mol Syndromol 2023; 1-8.
6.
Khayat MM, Hu J, Jiang Y, et al. AHDC1 missense mutations in Xia-Gibbs syndrome. HGG Adv 2021; 2: 100049.
7.
Cheng X, Tang F, Hu X, et al. Two Chinese Xia-Gibbs syndrome patients with partial growth hormone deficiency. Mol Genet Genomic Med 2019; 7: e00596.
8.
García-Acero M, Acosta J. Whole-exome sequencing identifies a de novo AHDC1 mutation in a Colombian patient with Xia-Gibbs syndrome. Mol Syndromol 2017; 8: 308-312.
9.
Gumus E. Extending the phenotype of Xia-Gibbs syndrome in a two-year-old patient with craniosynostosis with a novel de novo AHDC1 missense mutation. Eur J Med Genet 2020; 63: 103637.
10.
Yang H, Douglas G, Monaghan KG, et al. De novo truncating variants in the AHDC1 gene encoding the AT-hook DNA-binding motif- containing protein 1 are associated with intellectual disability and developmental delay. Cold Spring Harb Mol Case Stud 2015; 1: a000562.
11.
Chander V, Wangler M, Gibbs R, et al. Xia-Gibbs syndrome. In: Adam MP, Feldman J, Mirzaa GM, et al. (eds.). GeneReviews®. Seattle (WA): University of Washington, Seattle 1993–2024.
12.
Romano F, Falco M, Cappuccio G, et al. Genotype-phenotype spectrum and correlations in Xia-Gibbs syndrome: Report of five novel cases and literature review. Birth Defects Res 2022; 114: 759-767.
13.
Bosch DGM, Boonstra FN, de Leeuw N, et al. Novel genetic causes for cerebral visual impairment. Eur. J. Hum. Genet 2016; 24: 660-665.
14.
Jiang Y, Wangler MF, McGuire AL, et al. The phenotypic spectrum of Xia‐Gibbs syndrome. Am J Med Genet 2018; 176: 1315-1326.
15.
Cardoso‐Dos‐Santos AC, Oliveira Silva T, Silveira Faccini A, et al. Novel AHDC1 gene mutation in a Brazilian individual: Implications of Xia‐Gibbs syndrome. Mol Syndromol 2020; 11: 24-29.
16.
Ellis C, Pai GS, Wine Lee L. Atypical aplasia cutis in association with Xia Gibbs syndrome. Pediatr Dermatol 2021; 38: 533-535.
17.
Casanova D, Amar E, Bardot J, et al. Aplasia cutis congenita. Eur J Pediatr Surg 2001; 11: 280-284.
18.
Vanamo K, Härmä M. The shoelace method in congenital aplasia of the scalp and skull. Eur J Pediatr Surg 2005; 15: 425-7.
19.
Simman R, Priebe CJ Jr, Simon M. Reconstruction of aplasia cutis congenita of the trunk in a newborn infant using acellular allogenic dermal graft and cultured epithelial autografts. Ann Plast Surg 2000; 44: 451-454.
20.
Canter HI, Vargel I, Nasir S, et al. Use of a water-vapour permeable polyurethane film (omiderm) in the non-surgical treatment of aplasia cutis congenita. Scand J Plast Reconstr Surg Hand Surg 2004; 38: 232-235.
21.
Donati V, Arena S, Capilli G, Carrera G, Ciralli F, Liberatore A. Reparation of the severe case of aplasia cutis congenita with engineered skin. Biol Neonate 2001; 80: 273-276.
22.
Shivakumar SK, Dwarakanath S, Swaroop G, et al. Aplasia cutis congenita of the scalp: therapeutic modalities. Neurol India 2006; 54: 312-313.
23.
Izci Y, Gönül M, Secer HI, et al. Aplasia cutis congenita: a rare cutaneous sign of split cord malformations. Int J Dermatol 2007; 46: 1031-1035.
24.
Martinez-Lage JF, Almagro MJ, López Hernández F, et al. Aplasia cutis congenita of the scalp. Childs Nerv Syst 2002; 18: 634-637.
25.
Moros Peña M, Labay Matías M, Valle Sánchez F, et al. Aplasia cutis congenita in a newborn: etiopathogenic review and diagnostic approach. An Esp Pediatr 2000; 52: 453-456.
26.
Suarez E, Bertoli MJ, Eloy JD, et al. Case report and review of literature of a rare congenital disorder: Adams-Oliver syndrome. BMC Anesthesiol 2021; 21: 117.
27.
Hassed S, Li S, Mulvihill J, et al. Adams-Oliver syndrome review of the literature: Refining the diagnostic phenotype. Am J Med Genet A 2017; 173: 790-800.
28.
Sathishkumar D, Ogboli M, Moss C. Classification of aplasia cutis congenita: a 25-year review of cases presenting to a tertiary paediatric dermatology department. Clin Exp Dermatol 2020; 45: 994-1002.
29.
Collier A, Liu A, Torkelson J, et al. Gibbin mesodermal regulation patterns epithelial development. Nature 2022; 606: 188-196.
30.
Goyal C, Naqvi WM, et al. Xia-Gibbs syndrome: a review of literature. Cureus 2020; 12: e12352.
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