Stoneman Syndrome

Eisha Nasir


1st Year MBBS, Islamabad Medical and Dental College

Introduction

Stoneman syndrome is a very rare genetic disorder known as progressive bone fibro dysplasia (FOP) or severe progressive bone malformation. The ultra-rare autosomal dominant condition and disabling syndrome is defined by congenital deformity of the big toes and postnatal progressive heterotopic ossification of the connective tissue, especially those connected to the striated muscles, which can lead to lifelong disability.1 Ossification of the underlying soft tissues and fibroblastic proliferation in the neck or paravertebral region promote the development of rapidly growing masses. Although the soft tissue masses can grow on their own, trauma can speed their growth and cause calcification. Because FOP is often misdiagnosed, needless biopsies and operations are performed, which worsens the condition. Thus, it is crucial for early diagnosis that all doctors, surgeons, and pediatricians are aware of the clinical symptoms of FOP. 1
Fig 1

  1. Big toe is rotating inward or towards the other toes and the little toes adhering to one another
  2. Abnormalities of the upper spine, a short, broad neck

Symptoms

Progressive bone fibro dysplasia is a genetic connective tissue disorder that frequently affects ligaments, tendons, and skeletal muscles. It is linked to aberrant bone growth in many parts of the body. Stoneman syndrome is also characterized by further skeletal anomalies of the spine, neck, and ribs as well as aberrant bone formation in the afflicted areas of the neck, shoulder, elbows, knee joint, wrist, ankle, and mouth. Other abnormalities of the toes include the big toe rotating inward or towards the other toes, the little toes adhering to one another, and the fifth toe's persistent curvature. The proximal internal tibia, abnormalities of the upper spine, a short, broad neck, and short, aberrant thigh bones that stretch from the knee to the hip are some other congenital symptoms of stone man syndrome2


Causes

Stone man syndrome (FOP) is caused by a genetic mutation in the ACVR1 gene located on the long arm of chromosome 2 as 2q24.1. It participates in the stem cell fate-determining BMP receptor signaling pathway. Human BMPR receptors comprise BMPR1A, BMPR1B, BMPR2, and BMP4; only BMPR1A and BMP4 receptors play significant roles in the FOPsignaling pathway. The BMPR1A receptor is encoded by the bone marrow receptor protein (BMP), which is produced by the ACVR1 gene. The BMPR1Agene is located at position 10q23.2 on the long arm of chromosome 10. When the ACVR1 gene is altered, the codon 206 of the ACVR1 protein is changed from histidine to arginine amino acids. The aberrant activation of ACVR1 brought on by this amino acid alteration results in altered connective tissue and the convergence of muscle tissue to the secondary skeleton. The endothelial cells eventually undergo this transformation into mesenchymal stem cells, which later develop into bone 3

Spread

About 1 in 2 million babies globally are affected by fibro dysplasia ossificans progressiva. Almost 90% of patients with fibro dysplasia ossificans progressiva receive unnecessary therapies due to misdiagnosis and poor management. There have been roughly 700 recorded active cases so far throughout the world. The ACVR1 gene mutation test, radiological evaluation, and genetic analysis are all regarded as confirmatory methods for making an early diagnosis of the illness. Fibro dysplasia ossificans progressiva is a highly uncommon and incapacitating condition that, in the event of a false positive diagnosis, might result in wasteful surgical intervention and disastrous early impairment.Only 800 of the roughly 3,000 affected individuals worldwide have received official recognition for having human-stone syndrome. This disorder affects both men and women and all human relatives. . Although the actual frequency of this syndrome is unknown, the average incidence of the condition is 0.5 in 1 million or 1 in 2 million live births due to the disorder's extreme rarity.

Conclusions

A highly uncommon and incapacitating condition called fibro dysplasia ossificans progressiva can result in needless surgical intervention, early impairment, and disastrous outcomes if misdiagnosed. To improve these patients' quality of life, we need to educate doctors and patients' families about the illness, its symptoms for early diagnosis, and how to prevent flare-ups of the disease. 4

  1. Shah ZA, Rausch S, Arif U, El Yafawi B. Fibrodysplasia ossificans progressiva (stone man syndrome): a case report. J Med Case Rep. 2019 Dec 1; 13(1):364. doi: 10.1186/s13256-019-2297-z. PMID: 31785620; PMCID: PMC6885308.
  2. Asadi S, Aranian MR. the Role of Genetic Mutations in Genes ACVR1, BMPR1A, BMPR1B, BMPR2, BMP4 in Stone Man Syndrome. J Hematol Hemother 5: 008.


Volume 5
2023


An Official Publication of Student Spectrum at
Islamabad Medical & Dental College


Address of Correspondence

Eisha Nasir