Malignant infantile osteopetrosis is a rare osteosclerosing type of skeletal dysplasia that typically presents in infancy and is characterized by a unique radiographic appearance of generalized hyperostosis (excessive growth of bone). The generalized increase in bone density has a special predilection to involve the medullary portion with relative sparing of the cortices. Obliteration of bone marrow spaces and subsequent depression of the cellular function can result in serious hematologic complications. Optic atrophy and cranial nerve damage secondary to bony expansion can result in marked morbidity. The prognosis is extremely poor in untreated cases. Plain radiography provides the key information to the diagnosis. Clinical and radiologic correlations are also fundamental to the diagnostic process, with additional gene testing being confirmatory. Presentation
Hematologic manifestations related to bone marrow suppression and subsequent pancytopenia are a major source of morbidity and mortality. Additionally, extramedullary hematopoiesis can result in liver and spleen dysfunction. Cranial nerve dysfunction and neurologic complications are usually associated with infantile osteopetrosis. Expansion of the skull bone leads to macrocephaly. Additionally, linear growth retardation that is not apparent at birth, delayed motor milestones and poor dentition can occur. Diagnosis
Skeletal radiography
The generalized increase in bone density of the medullary portion predominates with relative sparing of the cortices. The axial and appendicular skeleton are uniformly involved.
In severe cases more testing may be required such as laparoscopy, intra-abdominal bacteria sampling and culturing, or tissue biopsy.Laparoscopy can visualize "violin-string" adhesions, characteristic of Fitz-Hugh–Curtis perihepatitis and other abscesses that may be present.Other imaging methods, such as ultrasonography, computed tomography (CT), and magnetic imaging (MRI), can aid in diagnosis. Blood tests can also help identify the presence of infection: the erythrocyte sedimentation rate (ESR), the C-reactive protein (CRP) level, and chlamydial and gonococcal DNA probes.Nucleic acid amplification tests (NAATs), direct fluorescein tests (DFA), and enzyme-linked immunosorbent assays (ELISA) are highly sensitive tests that can identify specific pathogens present. Serology testing for antibodies is not as useful since the presence of the microorganisms in healthy people can confound interpreting the antibody titer levels, although antibody levels can indicate whether an infection is recent or long-term.Definitive criteria include histopathologic evidence of endometritis, thickened filled Fallopian tubes, or laparoscopic findings. Gram stain/smear becomes definitive in the identification of rare, atypical and possibly more serious organisms. Two thirds of patients with laparoscopic evidence of previous PID were not aware they had PID, but even asymptomatic PID can cause serious harm. Laparoscopic identification is helpful in diagnosing tubal disease; a 65 percent to 90 percent positive predictive value exists in patients with presumed PID.Upon gynecologic ultrasound, a potential finding is tubo-ovarian complex, which is edematous and dilated pelvic structures as evidenced by vague margins, but without abscess formation.