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Autosomal recessive systemic microangiopathy associated with FANCL Fanconi anaemia
  1. Louis Cousyn1,2,
  2. Sophie Demeret3,
  3. Anne Philippi4,
  4. Françoise Bergametti5,
  5. Chiara Villa6,
  6. Patrizia Morbini7,
  7. Florence Riant8,
  8. Jean Soulier9,10,
  9. Elisabeth Tournier-Lasserve5,8,
  10. Christian Denier11
  1. 1 Department of Neurology, University Hospital Pitié-Salpêtrière, Paris, France
  2. 2 Sorbonne Université, Paris, France
  3. 3 Neuro-Intensive Care Unit, University Hospital Pitié-Salpêtrière, Paris, France
  4. 4 Institut Cochin, INSERM U1016, CNRS UMR-8104, Université Paris Cité, Paris, France
  5. 5 INSERM UMR 1141 NeuroDiderot, Université Paris Cité, Paris, France
  6. 6 Department of Neuropathology, University Hospital Pitié-Salpêtrière, Paris, France
  7. 7 Unit of Pathology, Department of Molecular Medicine, University of Pavia and Policlinico San Matteo Foundation IRCCS, Pavia, Italy
  8. 8 Service de Génétique Moléculaire Neurovasculaire, Saint Louis Hospital, Paris, France
  9. 9 Hematology Laboratory, Saint Louis Hospital, Paris, France
  10. 10 INSERM U944, Université Paris Cité, Paris, France
  11. 11 Department of Neurology, Bicêtre University Hospital, Le Kremlin-Bicêtre, France
  1. Correspondence to Dr Louis Cousyn, University Hospital Pitié Salpêtrière, Paris, France; louismarc.cousyn{at}

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Several hereditary cerebral microangiopathies with retinal vessels involvement have been described over the last decades, including mutations in COL4A1, TREX1, and more recently, CTC1 and STN1. Other systemic features have also been reported in these syndromes, including renal, hepatic, haematological, digestive or skin involvement, depending on the causative gene and the extent of the vasculopathy.1

We report here clinical, radiological, histopathological and genetic molecular data from a multiplex and consanguineous family from the Middle East, in which 5 of the 11 siblings developed cerebral microangiopathy with tumor-like lesions in a context of Fanconi anaemia.


The family comprised six obviously clinically affected siblings, of whom three were alive at examination. Parents—which were first cousins—and five other siblings were symptom-free (online supplemental figure 1). We reviewed clinical, biological and radiological data from the affected siblings.

Supplemental material


Two patients previously underwent brain biopsy and histological samples were available for only one of them.

DNA from both parents, three affected and two unaffected siblings was used for whole genome linkage analysis, and whole exome sequencing (WES) (see the Methods section in online supplemental material). In addition, DNA from one patient was used for direct Sanger sequencing of all exons of TREX1, CTC1, STN1 and SNORD118.

Supplemental material



A history of Fanconi anaemia with facial dimorphism including triangular face, low-set ears, ptosis, telecanthus and strabismus was reported in the six affected siblings (online supplemental table 1). Café-au-lait lesions were described in three of them, and one patient also had syndactyly and microcephaly. All affected patients had thrombocytopaenia (49–95 000/μL)—two also had an associated anaemia—and pathological chromosome breakage tests in blood. Besides, a typical FA core profile in blood and fibroblast cells, …

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  • LC and SD are joint first authors.

  • Contributors LC, SD, JS, ET-L and CD contributed to study conception, design, data collection, analysis, interpretation and draft manuscript preparation. AP, FB, CV, PM and FR contributed to data collection and analysis. All authors reviewed the results and approved the final version of the manuscript. Last authors: JS, ET-L and CD.

  • Funding The authors have not declared a specific grant for this research from any funding agency in the public, commercial or not-for-profit sectors.

  • Competing interests None declared.

  • Provenance and peer review Not commissioned; externally peer reviewed.

  • Supplemental material This content has been supplied by the author(s). It has not been vetted by BMJ Publishing Group Limited (BMJ) and may not have been peer-reviewed. Any opinions or recommendations discussed are solely those of the author(s) and are not endorsed by BMJ. BMJ disclaims all liability and responsibility arising from any reliance placed on the content. Where the content includes any translated material, BMJ does not warrant the accuracy and reliability of the translations (including but not limited to local regulations, clinical guidelines, terminology, drug names and drug dosages), and is not responsible for any error and/or omissions arising from translation and adaptation or otherwise.