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Congenital Zika syndrome with arthrogryposis: retrospective case series study

BMJ 2016; 354 doi: (Published 09 August 2016) Cite this as: BMJ 2016;354:i3899
  1. Vanessa van der Linden, paediatric neurologist1 2,
  2. Epitacio Leite Rolim Filho, paediatric orthpaedic surgeon1 3,
  3. Otavio Gomes Lins, clinical neurophysiologist3,
  4. Ana van der Linden, paediatric neurologist4,
  5. Maria de Fátima Viana Vasco Aragão, radiologist5 6,
  6. Alessandra Mertens Brainer-Lima, radiologist6 7,
  7. Danielle Di Cavalcanti Sousa Cruz, paediatrician4,
  8. Maria Angela Wanderley Rocha, paediatric infectologist8,
  9. Paula Fabiana Sobral da Silva, paediatric neurologist8,
  10. Maria Durce Costa Gomes Carvalho, paediatric neurologist8,
  11. Fernando José do Amaral, radiologist2,
  12. Joelma Arruda Gomes, paediatrician2,
  13. Igor Colaço Ribeiro de Medeiros, paediatrician9,
  14. Camila V Ventura, ophthalmologist10 11,
  15. Regina Coeli Ramos, paediatric infectologist8
  1. 1Association for Assistance of Disabled Children, AACD, Recife, Brazil
  2. 2Barão de Lucena Hospital, HBL, Recife, Brazil
  3. 3Federal University of Pernambuco, UFPE, Recife, Brazil
  4. 4Prof Fernando Figueira Integral Medicine Institute, IMIP, Recife, Brazil
  5. 5Centro Diagnóstico Multimagem, Recife, Brazil
  6. 6Mauricio de Nassau University, Recife, Brazil
  7. 7University of Pernambuco, UPE, Recife, Brazil
  8. 8Oswaldo Cruz University Hospital, HUOC, Recife, Brazil
  9. 9Hospital Infantil Jorge de Medeiros Recife, Brazil
  10. 10Altino Ventura Foundation, FAV, Recife, Brazil
  11. 11Pernambuco’s Eye Hospital, Recife, Brazil
  1. Correspondence to: V van der Linden vanessavdlinden{at}
  • Accepted 5 July 2016


Objective To describe the clinical, radiological, and electromyographic features in a series of children with joint contractures (arthrogryposis) associated with congenital infection presumably caused by Zika virus.

Design Retrospective case series study.

Setting Association for Assistance of Disabled Children, Pernambuco state, Brazil.

Participants Seven children with arthrogryposis and a diagnosis of congenital infection presumably caused by Zika virus during the Brazilian microcephaly epidemic.

Main outcome measures Main clinical, radiological, and electromyographic findings, and likely correlation between clinical and primary neurological abnormalities.

Results The brain images of all seven children were characteristic of congenital infection and arthrogryposis. Two children tested positive for IgM to Zika virus in the cerebrospinal fluid. Arthrogryposis was present in the arms and legs of six children (86%) and the legs of one child (14%). Hip radiographs showed bilateral dislocation in seven children, subluxation of the knee associated with genu valgus in three children (43%), which was bilateral in two (29%). All the children underwent high definition ultrasonography of the joints, and there was no evidence of abnormalities. Moderate signs of remodeling of the motor units and a reduced recruitment pattern were found on needle electromyography (monopolar). Five of the children underwent brain computed tomography (CT) and magnetic resonance imaging (MRI) and the remaining two CT only. All presented malformations of cortical development, calcifications predominantly in the cortex and subcortical white matter (especially in the junction between the cortex and white matter), reduction in brain volume, ventriculomegaly, and hypoplasia of the brainstem and cerebellum. MRI of the spine in four children showed apparent thinning of the cord and reduced ventral roots.

Conclusions Congenital Zika syndrome should be added to the differential diagnosis of congenital infections and arthrogryposis. The arthrogryposis was unrelated to the abnormalities of the joints themselves, but was possibly of neurogenic origin, with chronic involvement of central and peripheral motor neurones leading to deformities as a result of fixed postures in utero. Based on the neurophysiological observations, we suggest two possible mechanisms: tropism of neurones, with involvement of peripheral and central motor neurones, or a relation with vascular disorders.


  • Contributors: VvdL and ELRF coordinated all work and did most of the writing. VvdL, AvdL, PFSdS, and MDCGdC were responsible for the neurological data. ELRF was responsible for the orthopaedic data. OGL was responsible for the electromyographic data. RCR, MAWR, and DDCSC were responsible for laboratory data to exclude other congenital infections. FJdA was responsible for the ultrasonographic data. MdFVA and AMB-L helped to analyse brain and spinal cord imaging. CVV assisted with the ophthalmologic data. FJdA and ICRdM assisted the patients admitted to an intensive care unit. All authors reviewed and commented on drafts and approved the final manuscript and the decision to submit for publication. VvdL is the guarantor.

  • Competing interests: All authors have completed the ICMJE uniform disclosure form at and declare: no support from any organisation for the submitted work; no financial relationships with any organisations that might have an interest in the submitted work in the previous three years; no other relationships or activities that could appear to have influenced the submitted work.

  • Ethical approval: All investigations described were conducted as part of a clinical protocol approved by the Brazilian government and analysed retrospectively; no investigations were conducted for research reasons and, therefore, neither ethical approval nor informed consent was necessary.

  • Patient consent: The authors obtained written consent from parents for publication of the images in figures 1 to 4. All mothers gave consent for neuroimaging studies to be performed as part of the Brazilian microcephaly outbreak protocol or clinical indication. All seven cases have been deidentified, and we decided to proceed with publication in the interests of public health.

  • Data sharing: No additional data available.

  • Transparency: The lead author (VvdL) affirms that the manuscript is an honest,accurate and transparent account of the study being reported; that no important aspects of the study have been omitted.

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