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Original research
Endocrine and behavioural features of Lowe syndrome and their potential molecular mechanisms
  1. Cecilia Sena1,2,
  2. Grazia Iannello3,
  3. Alicja A Skowronski1,2,
  4. Katelyn Dannheim4,
  5. Leonard Cheung5,
  6. Pankaj B Agrawal6,
  7. Joel N Hirschhorn7,
  8. Phillip Zeitler8,
  9. Charles A LeDuc1,2,
  10. George Stratigopoulos1,2,
  11. Vidhu V Thaker1,2
  1. 1 Department of Pediatrics, College of Physicians and Surgeons, Columbia University, New York, New York, USA
  2. 2 Naomi Berrie Diabetes Center, Columbia University Irving Medical Center, New York, New York, USA
  3. 3 Columbia Stem Cell Initiative, Stem Cell Core, Columbia University Irving Medical Center, New York, New York, USA
  4. 4 Department of Pathology and Laboratory Medicine, Rhode Island and Hasbro Children’s Hospitals and the Warren Alpert Medical School of Brown University, Providence, Rhode Island, USA
  5. 5 Department of Human Genetics, University of Michigan Medical School, Ann Arbor, Michigan, USA
  6. 6 Division of Neonatology, Boston Children's Hospital, Boston, Massachusetts, USA
  7. 7 Division of Endocrinology, Boston Children's Hospital, Boston, Massachusetts, USA
  8. 8 Department of Endocrinology, Children's Hospital Colorado, Aurora, Colorado, USA
  1. Correspondence to Dr Vidhu V Thaker, Columbia University Irving Medical Center, New York, New York, USA; vvt2114{at}


Background Lowe syndrome (LS) is an X linked disease caused by pathogenic variants in the OCRL gene that impacts approximately 1 in 500 000 children. Classic features include congenital cataract, cognitive/behavioural impairment and renal tubulopathy.

Methods This study is a retrospective review of clinical features reported by family based survey conducted by Lowe Syndrome Association. Frequency of non-ocular clinical feature(s) of LS and their age of onset was summarised. An LS-specific therapy effectiveness scale was used to assess the response to the administered treatment. Expression of OCRL and relevant neuropeptides was measured in postmortem human brain by qPCR. Gene expression in the mouse brain was determined by reanalysis of publicly available bulk and single cell RNA sequencing.

Results A total of 137 individuals (1 female, 89.1% white, median age 14 years (range 0.8–56)) were included in the study. Short stature (height <3rd percentile) was noted in 81% (n=111) individuals, and 15% (n=20) received growth hormone therapy. Undescended testis was reported in 47% (n=64), and median age of onset of puberty was 15 years. Additional features were dental problems (n=77, 56%), bone fractures (n=63, 46%), hypophosphataemia (n=60, 44%), developmental delay and behavioural issues. OCRL is expressed in human and mouse hypothalami, and in hypothalamic cell clusters expressing Ghrh, Sst, Oxt, Pomc and pituitary cells expressing Gh and Prl.

Conclusions There is a wide spectrum of the clinical phenotype of LS. Some of the features may be partly driven by the loss of function of OCRL in the hypothalamus and the pituitary.

  • genetics, medical
  • endocrinology

Data availability statement

Data may be obtained from a third party and are not publicly available. Data can be requested from the Lowe Syndrome Association.

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Data availability statement

Data may be obtained from a third party and are not publicly available. Data can be requested from the Lowe Syndrome Association.

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  • Contributors Conceptualisation: VVT, PZ, PBA; data curation: PZ, VVT, CS; formal analysis: VVT, CS, AAS; investigation: CS, VVT, GS, CALeD, GI; resources: PZ, CALeD, GS, VVT, KD, JH; visualisation: CS, VVT, LC; writing-original draft: CS, VVT; guarantor: VVT; writing-review and editing: all authors.

  • Funding This work is supported in part by NIH-NIDDK K23 DK110539, Innovation Nucleation Fund and Louis V. Gerstner Scholar Programme at Columbia University Medical Center to VVT. CAL is supported in part by funding from the NIH-NIDDK R01 DK52431.

  • 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.