From neonatal signs to developmental delay: An infant with Wolf-Hirschhorn syndrome – a case study
DOI:
https://doi.org/10.63341/ijmmr/1.2025.85Keywords:
4p16.3 deletion, microcephaly, hypotonia, seizures, failure to thrive, Greek warrior helmet syndromeAbstract
Wolf-Hirschhorn syndrome (WHS) is a rare genetic disorder with significant developmental, metabolic and craniofacial manifestations, highlighting the importance of continued research due to these challenges. This case report presents an 8-month-old female infant, born at term but classified as small for gestational age, who exhibited developmental delays, metabolic abnormalities and craniofacial dysmorphology characteristic of WHS. This report aimed to emphasise the clinical progression and diagnostic difficulties encountered in cases of WHS. Comprehensive genetic analyses and clinical evaluations were conducted, confirming the diagnosis. Key findings included recurrent respiratory distress with multiple failed weaning attempts, severe failure to thrive, seizures, sensorineural hearing
loss, central hypotonia and feeding difficulties. Early neonatal complications and a prolonged, challenging stay in the neonatal intensive care unit were also noted, following which the infant was lost to follow-up until re-presenting at 8 months of age. This report underscores the necessity of early genetic screening and continuous follow-up for infants with congenital anomalies such as WHS. The findings may support paediatricians and neonatologists in the early identification and management of similar cases, thereby improving long-term outcomes
Received: 20.11.2024 | Revised: 06.03.2025 | Accepted: 27.05.2025
References
Paprocka J, Kaminiów K, Yetkin O, Tekturk P, Baykan B, Leiz S, et al. Clinical and epilepsy characteristics in WolfHirschhorn syndrome (4p-): A review. Seizure. 2024;116:14–23. DOI: 10.1016/j.seizure.2022.12.001
Corrêa T, Mayndra M, Santos-Rebouças CB. Distinct epileptogenic mechanisms associated with seizures in WolfHirschhorn syndrome. Mol Neurobiol. 2022;59(5):3159–69. DOI: 10.1007/s12035-022-02792-9
Gavril EC, Luca AC, Curpan AS, Popescu R, Resmerita I, Panzaru MC, et al. Wolf-Hirschhorn xyndrome: Clinical
and genetic study of 7 new cases, and mini review. Children. 2021;8(9):751. DOI: 10.3390/children8090751
Mills A, Bearce E, Cella R, Kim SW, Selig M, Lee S, et al. Corrigendum: Wolf-Hirschhorn syndrome-associated
genes are enriched in motile neural crest cells and affect craniofacial development in Xenopus laevis. Front Physiol.
;11:644596. DOI: 10.3389/fphys.2020.644596
Shannon NL, Maltby EL, Rigby AS, Quarrell OWJ. An epidemiological study of Wolf-Hirschhorn syndrome: Life
expectancy and cause of mortality. J Med Genet. 2001;38(10):674–9. DOI: 10.1136/jmg.38.10.674
Battaglia A, Carey JC. The delineation of the Wolf-Hirschhorn syndrome over six decades: Illustration of the
ongoing advances in phenotype analysis and cytogenomic technology. Am J Med Genet A. 2021;185(9):2748–55.
DOI: 10.1002/ajmg.a.62341
Berrocoso S, Amayra I, Lázaro E, Martínez O, López-Paz JF, García M, et al. Coping with Wolf-Hirschhorn syndrome:
Quality of life and psychosocial features of family carers. Orphanet J Rare Dis. 2020;15(1):293. DOI: 10.1186/s13023-
-01476-8
The World Medical Association. Declaration of Helsinki: Ethical Principles for Medical Research Involving Human
Subjects [Internet]. [cited 2024 November 3]. Available from: https://www.wma.net/what-we-do/medical-ethics/
declaration-of-helsinki/
World Health Organization. WHO child growth standards: Length/height-for-age, weight-for-age, weight-for-length,
weight-for-height, and body mass index-for-age: Methods and development. Geneva: World Health Organization;
312 P.
Bergemann AD, Cole F, Hirschhorn K. The etiology of Wolf-Hirschhorn syndrome. Trends Genet. 2005;21(3):188–
DOI: 10.1016/j.tig.2005.01.008
Maas NMC, Van Buggenhout G, Hannes F, Thienpont B, Sanlaville D, Kok K, et al. Genotype-phenotype correlation
in 21 patients with Wolf-Hirschhorn syndrome using high-resolution array comparative genome hybridisation
(CGH). J Med Genet. 2008;45:71–80. DOI: 10.1136/jmg.2007.052910
Zollino M, Di Stefano C, Zampino G, Mastroiacovo P, Wright TJ, Sorge G, et al. Genotype-phenotype
correlations and clinical diagnostic criteria in Wolf-Hirschhorn syndrome. Am J Med Genet. 2000;94(3):254–61.
DOI: 10.1002/1096-8628(20000918)94:3%3C254::AID-AJMG13%3E3.0.CO;2-7
Van Buggenhout G, Melotte C, Dutta B, Froyen G, Van Hummelen P, Marynen P, et al. Mild Wolf-Hirschhorn
syndrome: Micro-array CGH analysis of atypical 4p16.3 deletions enables refinement of the genotype-phenotype
map. J Med Genet. 2004;41(9):691–8. DOI: 10.1136/jmg.2003.016865
Blanco-Lago R, Málaga-Diéguez I, García-Peñas JJ, García-Ron A. Wolf-Hirschhorn syndrome. A series of 27
patients: Their epidemiological and clinical characteristics. The current situation of the patients and the opinions of
their caregivers regarding the diagnostic process. Rev Neurol. 2013;57(2):49. DOI: 10.33588/rn.5702.2013175
Battaglia A, Carey JC, South ST. Wolf-Hirschhorn syndrome: A review and update. Am J Med Genet C Semin Med
Genet. 2015;169(3):216–23. DOI: 10.1002/ajmg.c.31449
Ho KS, Markhama LM, Twedea H, Lortzc A, Olson LM, Sheng X, et al. A survey of antiepileptic drug responses
identifies drugs with potential efficacy for seizure control in Wolf-Hirschhorn syndrome. Epilepsy Behav. 2018;81:55–
DOI: 10.1016/j.yebeh.2017.12.008
Karalok ZS, Arhan EP, Erdogan KM, Gurkas E. Excellent response to levetiracetam in epilepsy with Wolf-Hirschhorn
syndrome. Childs Nerv Syst. 2016;32(1):9–11. DOI: 10.1007/s00381-015-2908-1
Lesperance MM, Grundfast KM, Rosenbaum KN. Otologic manifestations of Wolf-Hirschhorn syndrome. Arch
Otolaryngol Head Neck Surg. 1998;124(2):193–6. DOI: 10.1001/archotol.124.2.193
Ali MJ, Paulsen F. Syndromic and nonsyndromic systemic associations of congenital lacrimal drainage anomalies: A
major review. Ophthalmic Plast Reconstr Surg. 2017;33(6):399–407. DOI: 10.1097/IOP.0000000000000923
Boczek NJ, Lahner CA, Nguyen TM, Ferber MJ, Hasadsri L, Thorland EC, et al. Developmental delay and failure to
thrive associated with a loss-of-function variant in WHSC1 (NSD2). Am J Med Genet A. 2018;176(12):2798–802.
DOI: 10.1002/ajmg.a.40498
Antonius T, Draaisma J, Levtchenko E, Knoers N, Renier W, van Ravenswaaij C. Growth charts for Wolf-Hirschhorn
syndrome (0-4 years of age). Eur J Pediatr. 2008;167(8):807–10. DOI: 10.1007/s00431-007-0595-8
Downloads
Published
How to Cite
Issue
Section
License
Copyright (c) 2026 Jayakrishnan VY, Gokulakrishnan Parthasarathy, Aradhana Dwivedi, Vineeth VP
This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.
