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European Journal of Pediatrics

, Volume 173, Issue 4, pp 529–531 | Cite as

Primary hypothyroidism and nipple hypoplasia in a girl with Wolcott–Rallison syndrome

  • Anita Špehar Uroić
  • Vjosa Mulliqi Kotori
  • Nataša Rojnić Putarek
  • Vesna Kušec
  • Miroslav Dumić
Short Communication

Abstract

Wolcott–Rallison syndrome (WRS), caused by mutation in the EIF2AK3 gene encoding the PERK enzyme, is the most common cause of permanent neonatal diabetes mellitus (PNDM) in consanguineous families and isolated populations. Besides PNDM, it also includes skeletal abnormalities, liver and renal dysfunction, and other inconsistently present features. We present two siblings, who are WRS patients, and are Albanians from Kosovo born to unrelated parents. The older sister presented with PNDM, exocrine pancreatic insufficiency, short stature, microcephaly, normocytic anemia, delay in speech development, skeletal abnormalities, primary hypothyroidism, and hypoplastic nipples. Sequencing of the EIF2AK3 gene identified a homozygous mutation R902X in exon 13. The younger brother was diagnosed with PNDM and died from hepatic failure suggesting that he has been suffering from WRS as well. Including one previously reported patient from Kosovo carrying the same homozygous mutation, there are three WRS patients from this very small, ethnically homogenous region suggesting founder effect in this population. Conclusion: We postulate that thyroid hypoplasia with primary subclinical hypothyroidism already reported in two WRS patients and nipple hypoplasia could also be the phenotypic reflection of the mutation of pleiotropic EIF2AK3 gene in secretory cells.

Keywords

Wolcott–Rallison syndrome EIF2AK3 Primary hypothyroidism Nipple hypoplasia 

Notes

Acknowledgments

We are grateful to Sian Ellard and Elisabeth Young, Royal Devon, and Exeter National Health Service Healthcare Trust for molecular genetic analysis. We also thank Oscar Rubio-Cabezas for useful discussions.

Conflict of interest

The authors have no conflicts of interest.

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Copyright information

© Springer-Verlag Berlin Heidelberg 2013

Authors and Affiliations

  • Anita Špehar Uroić
    • 1
  • Vjosa Mulliqi Kotori
    • 2
  • Nataša Rojnić Putarek
    • 3
  • Vesna Kušec
    • 4
  • Miroslav Dumić
    • 3
  1. 1.Department of PediatricsUniversity Hospital Centre ZagrebZagrebCroatia
  2. 2.Pediatric Clinic Department of EndocrinologyUniversity Clinical Center KosovoPrishtinaKosovo
  3. 3.School of Medicine, Department of PediatricsUniversity Hospital Center ZagrebZagrebCroatia
  4. 4.School of Medicine, Clinical Institute of Laboratory DiagnosticUniversity Hospital Center ZagrebZagrebCroatia

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