Family Case Study Illuminates Variability in Jansen’s Disease Presentation

We are pleased to feature an intriguing and clinically important study by Dr. Sheela Nampoothiri from Amrita Research Hospital, Kerela, India, that brings fresh insight into the spectrum of Jansen’s metaphyseal chondrodysplasia (JMC), even among relatives carrying the same mutation.

In the paper “Jansen Metaphyseal Chondrodysplasia due to Heterozygous H223R‑PTH1R Mutations With or Without Overt Hypercalcemia”, researchers describe a unique family comprising a mother and her two sons, all affected by the H223R activating mutation in the PTH/PTHrP receptor (PTH1R).

Remarkably, while both children exhibited classic skeletal features of JMC,such as metaphyseal cupping, rickets-like changes, skull base sclerosis, and elevated calcium levels, their mother showed no overt hypercalcemia throughout her life, despite carrying the identical mutation

Key findings of the study include:

  • Diagnostic Challenges: The mother’s normal calcium levels prior to her sons’ diagnosis illustrate how JMC can go undetected in milder or atypical presentations.

  • Radiographic Consistency: All three individuals, the mother and her children, shared characteristic radiographic abnormalities, notably skull base sclerosis and metaphyseal changes, which proved critical for diagnosis.

  • Clinical Implications: This study emphasizes that hypercalcemia is not always a reliable marker for JMC, even in cases with the most common H223R mutation, and urges clinicians to rely also on radiographic evidence and family history when assessing suspected cases.

Why This STUDY Matters

  • It broadens the understanding of clinical variability in JMC, affirming that normal calcium levels do not rule out the disease.

  • It underscores the importance of thorough imaging and genetic testing, especially in families where one member is diagnosed, to ensure early recognition and appropriate care.

  • It raises an important question: Could other, yet undiagnosed individuals carry mild or atypical JMC due to the same mutation?