Ehlers Danlos Syndrome (EDS) is a heterogeneous group of connective tissue disorders resulting in varying degrees of skin fragility, skin hyperextensibility and joint hypermobility due to a defect in the structure, synthesis, or processing of collagen or biomolecules that interact with collagen.
1,2 There are many different types of EDS which are classified according to the new The 2017 International Classification of the Ehlers-Danlos Syndromes.
3 kEDS-PLOD1 (Kyphoscoliotic type) is an autosomal recessive disorder, its incidence being 1; 100,000 live births
4 which are caused due to mutations in the PLOD gene which encodes a collagen-modifying enzyme known as lysyl hydroxylase.
4,5 The disorder is characterized at birth by severe muscular hypotonia, kyphoscoliosis, marked joint hypermobility and subluxations, severe skin hyperelasticity, the fragility of the skin with abnormal scarring, osteopenia (without a tendency to fractures).
6 The sclera may be unusually fragile, to which even minor trauma may result in rupture of the sclera, cornea, and/or detachment of retina.
5 Our patient had blue sclera and retinal detachment in both eyes leading to vision loss and phthisis. However, our patient also had recurrent fractures which have not been described previously in kEDS-PLOD1. She also did not have skin hyperelasticity.
The major inherited cause of multiple fractures in childhood is the condition called Osteogenesis Imperfecta (OI). The features of OI are osteoporosis, fragile bones that fracture easily, ligament laxity and hypermobility of the joints. The estimated incidence is approximately 1/100,000 to 1/25,000.
7 Retinal detachment has also been described in OI.
8
Confirmatory molecular testing of kEDS-PLOD1 is dependent on the identification of homozygosity or compound heterozygosity for pathogenic variants in the PLOD1 gene that lead to a deficiency of the collagen-modifying enzyme Procollagen-lysine, 2-oxoglutarate 5-dioxygenase 1 (PLOD1 or LH1 [lysylhydroxylase1]).
4 Since the parents were not tested, it is not known if there is compound heterozygosity.
Thus, based even on the genetic report, it is not possible to confirm the diagnosis of ED type 6 in this child. It is always important to determine whether the heterozygous mutation is the cause of the disease by doing the genetic test in the parents.
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- Shipley M, Rahman A, O'Gradaigh D, Compston J. Skeletal dysplasia. In: Kumar P, Clark M, (eds). Kumar & Clark's Clinical Medicine. 7th ed. Edinburgh. Saunders Elsevier. 2009:568
- Mao J, Bristow J. The Ehlers-Danlos syndrome: on beyond collagens. J Clin Invest. 2001; 107: 1063–1069.
- Malfait F, Francomano C, Byers P, Belmont J, Berglund B, Black J, et al. The 2017 international classification of the Ehlers-Danlos syndromes. Am J Med Genet C Semin Med Genet. 2017;175:8-26.
- Yeowell HN, Steinmann B. PLOD1-Related Kyphoscoliotic Ehlers-Danlos Syndrome. In: Adam MP, Ardinger HH, Pagon RA, et al. (eds). GeneReviews [Internet]. Seattle (WA). University of Washington, Seattle; 1993-2019. Available from: https://www.ncbi.nlm.nih.gov/books/NBK1462/. Accessed on 26 December 2017.
- Ehlers Danlos Syndrome - NORD (National Organization for Rare Disorders) (Internet). NORD (National Organization for Rare Disorders). Available at: http://rarediseases.org/rare-diseases/ehlers-danlos-syndrome/. Accessed 22 June 2016
- Rohrbach M, Vandersteen A, Yis U, Serdaroglu G, Ataman E, Chopra M, et al. Phenotypic variability of the kyphoscoliotic type of Ehlers-Danlos syndrome (EDS VIA): clinical, molecular and biochemical delineation. Orphanet J Rare Dis. 2011;6:46.
- Basel D Steiner R. Osteogenesis imperfecta: Recent findings shed new light on this once well-understood condition. Genet Med. 2009;11:375-85
- Fleissig E, Barak A. Surgical management of retinal detachment in osteogenesis imperfecta: case report and review of the literature. Retin cases brief rep. 2019;13:43-46.
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