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Kyphoscoliotic type of Ehlers-Danlos Syndrome (EDS VIA) in six Egyptian patients presenting with a homogeneous clinical phenotype

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Abstract

The kyphoscoliotic type of the Ehlers-Danlos syndrome (EDS VIA) is a rare recessively inherited connective tissue disorder characterized by bruisable, hyperextensible skin, generalized joint laxity, severe muscular hypotonia at birth and progressive congenital scoliosis or kyphosis. Deficiency of the enzyme lysyl hydroxylase 1 (LH1) due to mutations in PLOD1 results in underhydroxylation of collagen lysyl residues and, hence, in the abnormal formation of collagen cross-links. Here, we report on the clinical, biochemical, and molecular findings in six Egyptian patients from four unrelated families severely affected with EDS VIA. In addition to the frequently reported p.Glu326_Lys585dup, we identified two novel sequence variants p.Gln208* and p.Tyr675*, which lead either to loss of function of LH1 or to its deficiency. All affected children presented with similar clinical features of the disorder, and in addition, several dysmorphic craniofacial features, not yet described in EDS VIA. These were specific for the affected individuals of each family, but absent in their parents and their unaffected siblings.

Conclusion: Our description of six patients presenting with a homogeneous clinical phenotype and dysmorphic craniofacial features will help pediatricians in the diagnosis of this rare disorder.

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Abbreviations

CT:

Computer tomography

EDS:

Ehlers-Danlos Syndrome

EDSVIA:

Kyphoscoliotic type of the Ehlers-Danlos Syndrome

EMG:

Electromyography

HP:

Hydroxylysyl-pyridinoline

LH1:

Lysyl hydroxylase 1

LP:

Lysyl-pyridinoline

NCV:

Nerve conduction velocity

PLOD1 :

Gene coding for procollagen-lysine, 2-oxoglutarate 5-dioxygenase 1

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Acknowledgments

We are particularly grateful to our patients and their families for participating in this study and giving us the permission to publishing their data and photographs. We thank Angelika Schwarze, Merima Mustedanagic, Véronique Rüfenach, and Christine Plüss for their technical support and contribution to biochemical and molecular analyses. This work has been supported by SNF grant Nr. 310030_138288.

Ethical standards

For all studies written, informed consent of the patients or their parents, in accordance with requirements of the Local Ethics Committee and the Helsinki Declaration of 1975, as revised in 2000, was obtained.

Conflict of interest

The authors declare that they have no conflict of interest.

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Authors and Affiliations

  1. Human Genetics Department, Medical Research Institute, Alexandria University, Alexandria, Egypt

    Ebtesam M. Abdalla, Mervat F. Elbelbesy & Amira Nabil

  2. Division of Metabolism, Connective Tissue Unit, University Children’s Hospital and Children’s Research Center (CRC) Zurich, Zurich, Switzerland

    Marianne Rohrbach, Céline Bürer & Cecilia Giunta

  3. Division of Endocrinology, Diabetes, and Clinical Nutrition, University Hospital, Basel, Switzerland

    Marius Kraenzlin

  4. Orthopedics Department, Menoufia Faculty of Medicine, Shebin al-Kom, Egypt

    Hazem El-Tayeby

Authors
  1. Ebtesam M. Abdalla
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  2. Marianne Rohrbach
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  3. Céline Bürer
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  4. Marius Kraenzlin
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  5. Hazem El-Tayeby
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  6. Mervat F. Elbelbesy
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  7. Amira Nabil
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  8. Cecilia Giunta
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Corresponding author

Correspondence to Cecilia Giunta.

Additional information

Communicated by Beat Steinmann

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Abdalla, E.M., Rohrbach, M., Bürer, C. et al. Kyphoscoliotic type of Ehlers-Danlos Syndrome (EDS VIA) in six Egyptian patients presenting with a homogeneous clinical phenotype. Eur J Pediatr 174, 105–112 (2015). https://doi.org/10.1007/s00431-014-2429-9

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  • DOI: https://doi.org/10.1007/s00431-014-2429-9

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