Elsevier

Legal Medicine

Volume 15, Issue 1, January 2013, Pages 23-27
Legal Medicine

Case Report
Respiratory complications of Ehlers–Danlos syndrome type IV

https://doi.org/10.1016/j.legalmed.2012.07.005Get rights and content

Abstract

We describe a case of Ehlers–Danlos syndrome (EDS) type IV in a male in early half in his twenties, who experienced recurrent and eventually fatal pulmonary hemorrhage. EDS type IV is a rare disorder of type III collagen synthesis that is characterized by unusual facies, thin translucent skin with a venous vascular pattern, easy bruising, and hypermobility of the small joints. Autopsy findings showed hypermobility of the joints and distensibility of the skin. Microscopically, the abdominal skin showed substantially decreased dermal thickness. Moreover, the reticular dermis showed fine collagen bundles and large interstitial spaces compared with the skin from a normal control that showed large collagen bundles. Individual elastic fibers were also thicker than those observed in the skin of a normal control. The thoracic aorta showed thin adventitia and a relative increase in elastic fibers. The parenchyma of both the lungs showed markedly diffuse hemorrhage with hemosiderin-laden alveolar macrophages or old thrombi and organized thrombi in the small bronchi. Furthermore, both sections of the lung showed multiple fibrous nodules containing benign metaplastic bone. Vascular wall disruption and tearing of the vessel walls in the lung parenchyma were also observed. We concluded that EDS type IV led to the patient’s death because of pulmonary hemorrhage. Because this syndrome resulted in the patient’s death from arterial and bowel rupture, it is important to consider EDS as a potential cause of sudden death.

Introduction

Ehlers–Danlos syndrome (EDS) is a group of inherited disorders involving abnormal production or secretion of collagen. EDS has three major clinical manifestations: hyperextensibility of the skin, hypermobility of the joints, and a bleeding tendency. EDS is classified into six types: classical, hypermobile, vascular, kyphoscoliosis, arthrochalasia, and dermatosparaxis [1]. EDS was originally reported to have an incidence rate of 1 in 150,000 individuals [2]. However, with the discovery of additional subtypes or variants of EDS, the frequency has now been reported to be 1 in 5000–10,000 [3]. Type IV is one of the rarest and clinically most serious EDS variants, because it is the only form of the disease with lethal complications. EDS type IV is characterized by thin transparent skin, easy bruising, and rupture of large arteries as well as bowel rupture, followed by death, which usually occurs in patients’ second decade of life [4], [5], [6], [7], [8].

Because patients with EDS mimic signs of abusive injuries and/or present with sudden infant death, forensic pathologists must be aware of this rare, autosomal-dominant connective tissue disorder.

Here, we describe the case of a male in early half in his twenties with EDS, who died suddenly while expectorating blood. We concluded that the decedent had EDS type IV.

Section snippets

Case history

A male in early half in his twenties experienced a severe cough and sneezing with repeated hemoptysis in the morning in his own room. His younger brother, who was in a nearby room, took notice of the strange circumstances and found his older brother in an unconscious state. The patient was brought to the emergency department by paramedics who responded to an emergency call for unresponsiveness. The patient arrived in a state of cardiopulmonary arrest, and despite medical treatment, he could not

Discussion

The sudden death of the decedent as well as his family and clinical history, including repeated hemoptysis, skin laxity, and joint hypermobility, strongly suggested that he had EDS type IV. Furthermore, autopsy findings were consistent with those of patients with EDS type IV as described below.

EDS type IV is inherited in an autosomal-dominant fashion. The disorder is caused by a mutation of the Col 3A1 gene, which results in abnormal type III collagen synthesis [9], [10], [11]. Thus, because of

References (24)

  • J. Lloyd et al.

    A T+6 to C+6 mutation in the donor splice site of Col 3A1 IVS7 causes exon skipping and results in Ehlers–Danlos syndrome type IV

    J Med Genet

    (1993)
  • D.M. Milewicz et al.

    Parental somatic and germ-line mosaicism for a multiexon deletion with unusual endpoints in a type III collagen (Col 3A1) allele produces Ehlers–Danlos syndrome type IV in the heterozygous offspring

    Am J Hum Genet

    (1993)
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