Dysosteosclerosis

Definition

Dysosteosclerosis is a skeletal dysplasia characterized by progressive osteosclerosis and platyspondyly.

Epidemiology

Less than 30 cases have been reported in the literature to date.

Cause

• The disease is caused by mutations in SLC29A33.
• This gene encodes a nucleoside transporter.
• Mutations in this gene may also cause Faisalabad histiocytosis, RosaÔ-Dorfman disease, H syndrome, and pigmented hypertrichosis with insulin-dependent diabetes mellitus syndrome .
• Parental consanguinity has been noted in some cases.

Inheritance

Dysosteosclerosis is inherited in an autosomal recessive manner, but an X-linked pedigree has also been reported.

Signs and symptoms

• The disease is characterized by sclerosis of the skull base, ribs, clavicles, scapulae, mid-diaphyses and increased bone fragility.
• Patients have a prominent forehead, narrow midface, flattening of the vertebral bodies and dental anomalies.
• Short stature, optic atrophy, hearing impairment, epilepsy, skin changes, and progressive psychomotor deficit are frequent.

For most diseases, symptoms will vary from person to person. People with the same disease may not have all the symptoms listed. 80%-99% of people have these symptoms

• Abnormal cranial nerve morphology
• Abnormality of dental ename(Abnormal tooth enamel)
• Cerebral calcification(Abnormal deposits of calcium in the brain)
• Coarse metaphyseal trabecularization
• Craniofacial hyperostosis(Excessive bone growth of the skull and face)
• Delayed eruption of teeth(Delayed eruption)
• Developmental regression(Loss of developmental milestones)
• Hearing impairment(Deafness)
• [[Hypertelorism](Wide-set eyes)
• Hypoplastic vertebral bodies(Underdeveloped back bones)
• Increased bone mineral density(Increased bone density)
• Intellectual disability(Mental deficiency)
• Irregular vertebral endplates
• Macrocephaly(Increased size of skull)
• Nystagmus(Involuntary, rapid, rhythmic eye movements)
• Optic atrophy
• Platyspondyly(Flattened vertebrae)
• Recurrent fractures(Increased fracture rate)
• Short stature(Decreased body height)
• Ventricular septal defect(Hole in heart wall separating two lower heart chambers)

30%-79% of people have these symptoms

• Aplasia/Hypoplasia of the skin(Absent/small skin)

Diagnosis

• Diagnosis is based on clinical features like frontal bossing, blue sclera, normal teeth, genu valgum, and unremarkable joints.
• Radiographs shows orbital and facial sclerosis, basilar thickening, bone-in-bone appearance of the pelvis, sclerotic long bone ends, and fractures of ribs and extremities.
• Progressive metaphyseal widening occurrs as vertebrae changed from ovoid to flattened and became beaked anteriorly.
• A hemogram was normal. Consistent with OPT, serum parathyroid hormone (PTH) concentrations reflected dietary calcium levels.
• Serum bone alkaline phosphatase, osteocalcin, and TRACP-5b were subnormal.
• The iliac crest contained excessive primary spongiosa and no osteoclasts.

Treatment

• Overall the disease has a poor prognosis, with treatment mainly focusing on palliation and comfort care.
• As the mechanism and clinical course of DSS remains unclear, definitive treatment is not available for patients. Bone marrow transplant may improve skeletal abnormalities, however it is improbable the transplant will ameliorate the unexplained neurological deteriorations.
• In addition, the surgery may not be suitable for every patients as the underlying genetic cause of the disease varies amongst patients.
• Advice of control and reduction in excessive calcium intake may be recommended by physicians to ensure circulating levels of parathyroid hormones are normal to induce and maintain bone resorption.

NIH genetic and rare disease info

• NIH info on Dysosteosclerosis

Dysosteosclerosis is a rare disease.

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