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STAT5b gain-of-function disease in a child with mycobacterial osteomyelitis of the skull: rare presentation of an emerging disease entity

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Abstract

Purpose

STAT proteins play a key role in several cellular functions related to cell development, differentiation, proliferation, and survival. Persistent STAT activation due to somatic STAT5bN642H gain-of-function mutation is a rare mechanism of STAT dysregulation that results in hypereosinophilia, frequent infections, leukemias, and pulmonary diseases. Herein, we describe a case of a child with a rare early onset STAT5b gain-of-function disease treated with targeted JAK inhibition who developed a cranial Mycobacterium avium osteomyelitis.

Methods

A 3-year-old male with a known STAT5b gain-of-function mutation presented with a 10-day history of a firm, immobile, non-painful cranial mycobacterium mass with dural infiltration located anterior to the coronal suture. Stepwise management finalized with complete resection of the lesion with calvarial reconstruction. A case-based literature review was performed evaluating all patients with this mutation who developed cranial disease.

Results

The patient was symptom and lesion-free at 1 year since surgical resection and initiation of triple mycobacterial pharmacotherapy. Our literature review demonstrated the rarity of this disease, as well as other presentations of this disease in other patients.

Conclusion

Patients with STAT5b gain-of-function mutations have attenuated Th1 responses and are treated with medications, such as JAK inhibitors, which further inhibit other STAT proteins that regulate immunity against rare infectious entities, such as mycobacterium. Our case highlights the importance of considering these rare infections in patients on JAK inhibitors and with STAT protein mutations. Possessing a clear mechanistic understanding of this genetic mutation, its downstream effect, and the consequences of treatment may enhance a physician’s diagnostic and clinical management of similar patients in the future.

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Abbreviations

STAT5b:

Signal Transducer and Activator of Transcription 5b

GOF:

Gain-of-function

GH:

Growth hormone

JAK:

Janus Kinase

PTCL:

Peripheral T-cell lymphoma

T-ALL:

T-cell acute lymphoblastic leukemia

IFN-ϒ:

Interferon gamma

HES:

Hypereosinophilia syndrome

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Authors and Affiliations

  1. Department of Neurosurgery, Montefiore Medical Center and the Albert Einstein College of Medicine, 3316 Rochambeau Ave, Bronx, NY, 10467, USA

    Andrew J. Kobets, Samuel Ahmad, Andre Boyke, Ryan Holland & Rick Abbott

  2. University of Nairobi School of Medicine, Nairobi, Kenya

    David Oriko

  3. Department of Pediatrics, Montefiore Medical Center and the Albert Einstein College of Medicine, Bronx, NY, USA

    Rachel Eisenberg

  4. Department of Neurosurgery, Tabriz University of Medical Sciences, Tabriz, Iran

    Seyed Ahmad Naseri Alavi

Authors
  1. Andrew J. Kobets
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  2. Samuel Ahmad
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  7. Seyed Ahmad Naseri Alavi
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Contributions

AJK, SA, AB, DO, RH, RE were involved in the composition of this manuscript and AJK, RE, RA were involved in revision and review of this manuscript. AJK and RA developed the concept for this report.

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Correspondence to Andrew J. Kobets.

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Approval for the publication of this work was granted by the Albert Einstein IRB and consent to publish this report was obtained from the patient’s family.

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Kobets, A.J., Ahmad, S., Boyke, A. et al. STAT5b gain-of-function disease in a child with mycobacterial osteomyelitis of the skull: rare presentation of an emerging disease entity. Childs Nerv Syst 39, 2071–2077 (2023). https://doi.org/10.1007/s00381-023-05997-y

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