An Unusual Cause of Peroneal Neuropathy
Introduction
Ehlers-Danlos syndrome encompasses a group of inherited connective tissue disorders, best known for joint hypermobility and skin hyperextensibility. These well-recognized signs are not as apparent in type IV, the vascular type. The clinical diagnosis of Ehlers-Danlos syndrome type IV (EDS4; OMIM1300500) is based on 4 clinical criteria, which include (1) thin, translucent skin, (2) easy bruising, (3) characteristic facial appearance (acrogeria), and (4) rupture of arteries, intestines, and uterus. EDS4 is estimated to represent 5%-10% of cases of Ehlers-Danlos.1 Perhaps because of this rarity, the diagnosis is often made only after serious vascular complications, which carry high morbidity and mortality.2, 3 Joint contractures, peripheral neuropathy, and other neurologic manifestations of EDS4 are described in rare individuals with this condition. Here, we discuss the case of a young girl who initially presented with neurologic symptoms suggestive of a peripheral neuropathy before the development of vascular complications associated with EDS4, including central arteriovenous fistula. Whole exome sequencing (WES) was performed, which excluded primary or concurrent neurologic disease and identified a novel mutation in COL3A1, consistent with the diagnosis of EDS4.
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Case Report
The patient initially presented at the age of 15 years with findings suggestive of bilateral peroneal motor neuropathy with pes equinus contractures and lower extremity muscle atrophy (Fig. 1). In addition, she had a history of easy bruising and bleeding along with poor wound healing. She additionally reported intermittent headaches characterized as mild migrainous headaches well controlled with amitriptyline. Physical examination revealed transparent skin with visible veins over her back and
Discussion
EDS4 is inherited in an autosomal-dominant fashion from mutations of the type III procollagen gene, COL3A1.2 Approximately 95% of the mutations result in the production of abnormal type III procollagen. There are 2 major mutation types: point mutations resulting in substitutions of glycine for another amino acid in the triple-helical domain and splice site mutations.1, 2, 4 Our patient had a novel point mutation resulting in the substitution of a glycine residue for aspartic acid in this
Conclusion
EDS4 is a form of Ehlers-Danlos disease that is associated with significant morbidity and mortality. Patients may first present to a neurologist׳s attention owing to vascular complications, involving the CNS. EDS4 may also have more indolent neurologic complications, which may be unrecognized when not associated with vascular findings. Prompt diagnosis can aid in rapid recognition of the potentially catastrophic complications and help delineate increased risks involved in surgical or
References (18)
- et al.
COL3A1 haploinsufficiency results in a variety of Ehlers-Danlos syndrome type IV with delayed onset of complications and longer life expectancy
Genet Med
(2011) - et al.
Diagnosis of vascular Ehlers-Danlos syndrome in Italy: Clinical findings and novel COL3A1 mutations
J Dermatol Sci
(2011) - et al.
Multiple strokes and bilateral carotid dissections: A fulminant case of newly diagnosed Ehlers-Danlos syndrome type IV
J Neurol Sci
(2012) - et al.
Intracranial aneurysms in Ehlers-Danlos syndrome type IV in early childhood
Pediatr Neurol
(2001) - et al.
The spectrum, management and clinical outcome of Ehlers-Danlos syndrome type IV: A 30-year experience
J Vasc Surg
(2005) - et al.
Peripheral neuropathy in Ehlers-Danlos syndrome
Pediatr Neurol
(1995) - et al.
Effect of celiprolol on prevention of cardiovascular events in vascular Ehlers-Danlos syndrome: A prospective randomised, open, blinded-endpoints trial
Lancet
(2010) - et al.
Cerebrovascular complications in Ehlers-Danlos syndrome type IV
Ann Neurol
(1995) - et al.
Clinical and genetic features of Ehlers-Danlos syndrome type IV, the vascular type
N Engl J Med
(2000)