On the curious association of diaphragmatic hernia and Urban-Rifkin-Davis Syndrome (Autosomal Recessive Cutis Laxa-1C): A collective review of 16 cases


  • V Raveenthiran Professor of Pediatric Surgery, SRM University, Chennai
  • Nagarajan Darun Government Cuddalore Medical College, Chidambaram
  • Dhayalan Pavithra Lifecell Diagnostics, Keelakottaiyur, Chennai, India
  • Prakash Gambhir Lifecell Diagnostics, Keelakottaiyur, Chennai, India




Cutis laxa, Urban Rifkin Davis syndrome, Diaphragmatic hernia, Hiatus hernia, Respiratory distress, Genetic mutation


Background: Autosomal recessive cutis laxa type-1C is also known as Urban-Rifkin-Davis syndrome (URDS). It is known to affect cardiopulmonary, integumentary, gastrointestinal, musculoskeletal and genitourinary systems. However, its frequent association with congenital diaphragmatic hernia has not previously been highlighted.

Case Presentation: A newborn male with cutis laxa presented with respiratory distress at birth. The cause of dyspnoea was perinatal strangulation of the stomach in hiatus hernia. After surgical repair of the hernia, his respiratory distress temporarily improved but kept recurring periodically by various mechanisms in sequence namely pulmonary hypertension, tracheomalacia, pulmonary emphysema and finally he succumbed to pneumothorax. Genetic analysis revealed his skin condition as autosomal recessive cutis laxa type-1C which is also known as URDS. Exome sequencing revealed a novel frameshift mutation c.426delC (p.Cys143Alafs*41) of the LTBP4 gene in the exon 5 of Chromosome 19. 

Conclusion: Out of the 28 cases of URDS reported in the world literature 57% had congenital diaphragmatic hernia (CDH) and 53% of them died during infancy. Such a high incidence of CDH is not observed in other subtypes of elastic disorders. Thus, congenital diaphragmatic defects appear to be a characteristic diagnostic feature of URDS in patients with cutis laxa.


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Author Biographies

Nagarajan Darun, Government Cuddalore Medical College, Chidambaram

Postgraduate Student

Department of Pediatric Surgery

Dhayalan Pavithra, Lifecell Diagnostics, Keelakottaiyur, Chennai, India

Consultant Geneticist


Prakash Gambhir , Lifecell Diagnostics, Keelakottaiyur, Chennai, India

Consultant Geneticist


Beyens A, Boel A, Symoens S, Callewaert B. Cutis laxa: A comprehensive overview of clinical characteristics and pathophysiology. Clin Genet. 2021; 99: 53-66. doi:10.1111/cge.13865

Berk DR, Bentley DD, Bayliss SJ, Lind A, Urban Z. Cutis laxa: a review. J Am Acad Dermatol. 2012; 66: 842. e1-17. doi: 10.1016/j.jaad.2011.01.004

Urban Z. LTBP4 and autosomal recessive cutis laxa type 1C. In: Erickson RP, Wynshaw-Boris AJ. Epstein's inborn errors of development: the molecular basis of clinical disorders of morphogenesis. 3edn. Oxford: Oxford University Press. 2016; 431-434

Urban Z, Hucthagowder V, Schurmann N, et.al. Mutations in LTBP4 cause a syndrome of impaired pulmonary, gastrointestinal, genitourinary, musculoskeletal, and dermal development. Am J Hum Genet. 2009; 85: 593-605. doi:10.1016/j.ajhg.2009.09.013

Callewaert B, Su CT, Van Damme T, et.al. Comprehensive clinical and molecular analysis of 12 families with type 1 recessive cutis laxa. Hum Mutat. 2013; 34: 111-21. doi:10.1002/humu.22165

Su CT, Huang JW, Chiang CK, et.al. Latent transforming growth factor binding protein 4 regulates transforming growth factor beta receptor stability. Hum Mol Genet. 2015; 24: 4024-36. doi:10.1093/hmg/ddv139

Ritelli M, Cammarata-Scalisi F, Cinquina V, Colombi M. Clinical and molecular characterization of an 18-month-old infant with autosomal recessive cutis laxa type 1C due to a novel LTBP4 pathogenic variant, and literature review. Mol Genet Genomic Med. 2019; 7: e00735. doi:10.1002/mgg3.735

Gupta N, Langeh N, Sridharan A, Kabra M. Identification of a novel 19-bp deletion mutation in LTBP4 using exome sequencing in two siblings with autosomal recessive cutis laxa type 1C. J Pediatr Genet. 2020; 9: 125-131. doi:10.1055/s-0039-1698806

Melo MS, Ferreira SL, Nunes S, et.al. A novel case of autosomal recessive cutis type 1C: Case report and literature review. 24th Annual Meeting of Sociedade Portuguesa de Genetica Humana. Nov 20, 2020 (virtual)

Albayrak HM, Emiralioglu N, Damar C. Overview of the pulmonary manifestations in patients with autosomal recessive cutis laxa type-1C. Pediatr Allergy Immunol Pulmonol. 2020; 33: 207-212. doi:10.1089/ped.2020.1156

Zhang Q, Qin Z, Yi S, et.al. Two novel compound heterozygous variants of LTBP4 in a Chinese infant with cutis laxa type-1C and a review of the related literature. BMC Med Genomics. 2020; 13: 183 (9 pages). doi:10.1186/s12920-020-00842-6

Mazaheri M, Jahantigh HR, Yavari M, Mirjalili SR, Vahidnezhad H. Autosomal recessive cutis laxa type 1C with a homozygous LTBP4 splicing variant: a case report and update of literature. Mol Biol Rep. 2022; 49: 4135-40. doi:10.1007/s11033-022-07454-6

Ravel JM, Comel M, Wandzel M, et.al. First report of a short in-frame biallelic deletion removing part of the EGF-like domain calcium-binding motif in LTBP4 and causing autosomal recessive cutis laxa type-1C. Am J Med Genet A. 2022; 188: 3343-49. doi:10.1002/ajmg.a.62954

Su CT, Urban Z. LTBP4 in health and disease. Genes (Basel). 2021; 12: 795. doi:10.3390/genes12060795

Abdul-Wahab A, Janahi IA, Eltohami A, Zeid A, Faiyaz-Ul-Haque M, Teebi AS. A new type of Ehlers-Danlos syndrome associated with tortuous systemic arteries in a large kindred from Qatar. Acta Paediatr. 2003; 92: 456-62. doi: 10.1111/j.1651-2227.2003.tb00578.x

Beck TF, Campeau PM, Jhangiani SN, et.al. FBN1 contributing to familial congenital diaphragmatic hernia. Am J Med Genet A. 2015; 167A: 831-6. doi: 10.1002/ajmg.a.36960

Brosens E, Peters NCJ, van Weelden KS, et.al. Unraveling the genetics of congenital diaphragmatic hernia: an ongoing challenge. Front Pediatr. 2022; 9: 800915. doi: 10.3389/fped.2021.800915

Schreiner Y, Schaible T, Rafat N. Genetics of diaphragmatic hernia. Eur J Hum Genet. 2021; 29: 1729-1733. doi: 10.1038/s41431-021-00972-0

Bendixen C, Reutter H. The role of de novo variants in patients with congenital diaphragmatic hernia. Genes 2021; 12: 1405. doi: 10.3390/genes12091405

Bielinska M, Jay PY, Erlich JM, Mannisto S, Urban Z, Heikinheimo M, Wilson DB. Molecular genetics of congenital diaphragmatic defects. Ann Med 2007; 39: 261-74. doi: 10.1080/07853890701326883

Bultmann-Mellin I, Dinger K, Debuschewitz C, et.al. Role of LTBP4 in alveolarization, angiogenesis, and fibrosis in lungs. Am J Physiol Lung Cell Mol Physiol. 2017; 313: L687-L698. doi:10.1152/ajplung.00031.2017

Yoshihara T, Takaragawa M, Dobashi S, Naito H. Losartan treatment attenuates hindlimb unloading-induced atrophy in the soleus muscle of female rats via canonical TGF-β signaling. J Physiol Sci. 2022; 72: 6. doi:10.1186/s12576-022-00830-8




How to Cite

Raveenthiran V, Darun N, Pavithra D, Gambhir P. On the curious association of diaphragmatic hernia and Urban-Rifkin-Davis Syndrome (Autosomal Recessive Cutis Laxa-1C): A collective review of 16 cases. J Neonatal Surg [Internet]. 2024Mar.22 [cited 2024Jul.21];13:15. Available from: https://jneonatalsurg.com/ojs/index.php/jns/article/view/1290

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