(Marble bones disease, osteopetrosis disease)

Osteopathy of autosomal dominant or recessive transmission. It is due to a deficiency in osteoclasts that prevents physiologic bone resorption. The prevalence of the dominant forms, linked to a mutation of the CLCN7 gene (16p13), is around 1/20 000.

Several forms:

-         autosomal dominant type I: (OPTA1) [MIM 607 634]: mutation of LRP5 gene (11q13.2); decrease of number of osteoclasts;  low risk of fracture - the skull is more frequently involved; few symptoms but it may cause pain and a progressive deafness

-         autosomal dominant type II (OPTA2) ((MIM 166600), strictly speaking Albers-Schönberg disease): mutation of  the CLNC7 gene (16p13); proliferation of large polynuclear osteoclasts; prevalence of ± 1/20.000; osteoslerosis involves mostly the skull basis and the vertebrae; the risk of fracture is important; the diagnosis is generally made when the patient is adult

-        autosomal dominant type III (OPTA3) [MIM 618 107], mutation of the PLEKHMI gene (17q21) that can also cause a recessive form named OPBT6: this form is hardly symptomatic but cause a premature arthrosis; surgery is more difficult and bloodier than on healthy bone.

The dominant autosomal forms are less symptomatic (fractures, scoliosis) and usually discovered in adulthood

Some autosomal recessive forms (see Osteopetroses; autosomal recessive) among which:

-        benign autosomal recessive form or OPTB3: bone sclerosis, cerebral calcifications and tubular acidosis, very rare, due to a mutation of the AC2 gene (8q21)

-        autosomal recessive known as 'malignant osteopetrosis' or OPTB1 (very rare: 1/250,000), due to a mutation of the TCIRG1  (11q13.2) gene causing a suboptimal osteoclastic function leading to:

o         macrocephaly, hypertelorism, prominent forehead, sclerosis and enlargement of the lower jaw, temporomandibular ankylosis, progressive choanal stenosis

o         respiratory and feeding difficulties, early tooth decay

o         hematological complications (pancytopenia caused by bony invasion of the medullary cavities); hepatosplenomegaly (extra-medullary hematopoeisis)

o         neurological complications: (progressive blindness and deafness, facial palsy, intracranial hypertension

 o         hypocalcemia with occasional tetanic spasms, secondary hyperparathyroidism

 Anesthetic implications: 

careful positioning due to the risk of pathological fractures in all forms. Difficult intubation (mandibular hypoplasia). Fragile teeth. Hypocalcemia. Sometimes pancytopenia ("malignant" osteopetrosis) requiring bone marrow transplant (curative if early).

References : 

• Burt N, Haynes GR, Bailey MK. 
  Patients with malignant osteopetrosis are at high risk of anesthetic morbidity and mortality.
  Anesth Analg 1999; 88:1292-7.
• Basaranoglu G, Erden V. 
  Difficult tracheal intubation of a patient with cervical fracture due to osteopetrosis. 
  Pediatr Anesth 2001; 11: 745.
• Burgoyne LL, Kaur A, Billups CA, Parish M-E, Kaddoum RN, Bikhazi BG, Pereiras LA.
  Complications of anesthesia for children with malignant osteopetrosis before and after hematopoietic stem cell transplantation. 
  Pediatr Anesth 2010; 20: 1046-51. 
• Ba ID, Ba A, Thiongane A, Ly/Ba A et al.
  Ostéopétrose maligne révélée par une atrésie des choane : à propos d’un cas.
  Arch Pédiatr 2016 ; 23 :514-8.
• Orphananesthesia.
  Anaesthetic recommandations for patients suffering from osteopetrosis.
  Orphananesthesia.eu
• Soberon JR, Arzillo S, Myers SL, King JJ.
  Osteopetrosis - Anesthetic considerations for total knee arthroplasty : a case report.
  A&A Practice 2019 ; 12 : 5-8

Updated: January 2019