Case Report of Worth Syndrome and Chiari I Malformation: Unusual Association and Surgical Treatment.

BACKGROUND: Worth syndrome or autosomal dominant endosteal hyperostosis (ADEH) is an extremely rare genetic disease involving increased bone density. To the author's knowledge, this is the second case report of a family with neurologic involvement associated with this condition along with its surgical treatment. The most effective treatment for clinically significant neurologic symptoms in this scenario is currently unknown, and there is sparse experience on surgical treatment for this condition reported in the literature. Therefore we aim to make a contribution to the identification of a standard and consistently successful surgical management. CASE DESCRIPTION: Two patients, mother (Patient 1) and daughter (Patient 2), were diagnosed with Worth syndrome. Both presented with the typical facial characteristics described for ADEH. Interestingly, Patient 1 presented the novel mutation in the LRP5 gene that is associated with different conditions involving increased bone density. Although neurologic symptoms are infrequent in ADEH, both referred chronic headache, nausea, and vomiting. Neuroimaging showed an increased cranial bone density and Chiari I malformation. The patients underwent a midline suboccipital craniectomy with excision of the posterior arch of C1 and duroplasty. However, due to a symptomatic recurrence 5 years after surgery, Patient 1 was reoperated on. We extended the craniectomy and also carried out a C2 laminectomy. CONCLUSION: After surgical interventions, patients' neurologic symptoms were successfully resolved. This report shows that posterior fossa decompression including duroplasty may be a valid treatment option in case of neurologic involvement.

Hyperphosphatemic familial tumoral calcinosis: odontostomatologic management and pathological features.

BACKGROUND: Hyperphosphatemic familial tumoral calcinosis (HFTC) is to a rare autosomal recessive disorder characterized by cutaneous and sub-cutaneous calcified masses, usually adjacent to large joints. The aim of the current study was to report on the clinico-pathological features of a patient with HFCT, with emphasis on alterations in the jawbones and teeth and the subsequent therapeutic interventions. CASE REPORT: A 13-year-old male patient with HFTC diagnosis came to our attention for dental anomalies and maxillary and mandibular hypoplasia. OPT highlighted multiple impacted teeth, short and bulbous teeth, and pulp chamber and canal obliterations. Lateral cephalometric radiograms pointed out retrusion of both jaws, skeletal class II malocclusion, and deep-bite. He underwent orthopedic, orthodontic, conservative, and surgical treatments, allowing the correction of maxillo-facial and dental abnormalities and dysmorphisms without adverse effects. The surgical samples were sent for conventional and confocal laser scanning microscope (CLSM) histopathological examination, which highlighted several metaplastic micro- and macro-calcifications in the soft tissues, and typical islands of homogenous, non-tubular, dentino-osteoid calcified structures in dentinal tissues. CONCLUSIONS: The management of maxillo-facial abnormalities in patients affected by HFTC is very difficult and, requires a combined therapeutic approach. To date, very few indications have been published in the literature.

Hyperphosphatemic familial tumoral calcinosis: response to acetazolamide and postulated mechanisms.

Hyperphosphatemic familial tumoral calcinosis (HFTC) is characterized by enhanced renal phosphate absorption, hyperphosphatemia, and tumor-like extraosseous calcifications due to inactivating mutations in FGF23 or associated proteins. Surgical excision is needed when low phosphate diet and phosphate binders are ineffective. Sporadic reports have supported acetazolamide use. We report on a 7-year-old African American boy who presented with severe HFTC requiring numerous surgical excisions. Tumors continued to appear and others reoccurred despite phosphate restriction and sevelamer carbonate. At the age of 9.5 years, acetazolamide (40 mg/kg/day) was added and resulted in mild metabolic acidosis (bicarbonate 25.3 mEq/L vs. 21.4 mEq/L, P < 0.001; serum pH 7.38 vs. 7.31, P = 0.013, pre- and post-acetazolamide, respectively) but no change in tubular reabsorption of phosphate (TRP) (96.9% vs. 95.9%, P = 0.34) or serum phosphate (6.6 mg/dl vs. 6.9 mg/dl, P = 0.52 pre- and post-acetazolamide, respectively). Following the initiation of acetazolamide therapy, the patient experienced significant improvement in disease course as indicated by resolution of localized bone pain, cessation of tumor formation, and no tumor recurrence. Despite mild metabolic acidosis, our patient had improved linear growth and did not develop any other side effects related to therapy. Intact FGF23 remained abnormally low throughout disease course, while C-terminal FGF23 increased with acetazolamide. We conclude that acetazolamide can control severe HFTC by inducing mild metabolic acidosis despite no change in serum phosphate or TRP. This effect may be exerted though improved calcium-phosphate complex solubility and increased FGF23 locally.

[Van Buchem disease. Maxillofacial changes, diagnostic classification and general principles of treatment]. / Malattia di Van Buchem. Alterazioni maxillo facciali, inquadramento diagnostico e principi generali di trattamento chirurgico.

Van Buchem's disease is a rare pathology with recessive transmission and variable expressivity characterised by a progressive cortical bone deposition. There are two types of this disease: Type I (Van Buchem's disease) progressive form for all life and with high level of PA (alkaline phosphate); Type II (Worth disease) the pathologic bone deposition stops at 20 years of age and the level of PA in the adult is normal. The most important histological feature is the bone hypertrophy with preservation of the lamellar frame. The bones interested are: skull vault, mandible, ribs, clavicle and diaphyseal portion of long bones. The first clinical manifestation became evident in childhood with progressive course. The narrowing of the cranial foramen is responsible of the progressive cranial nerves compression and the subsequent neurological signs. The disease is incurable; surgical treatment aims to reduce the intracranial pressure and to correct bones deformity. A clinical case in which the patient treated has esthetic problems but not neurological signs is presented.

Hyperostosis corticalis generalisata: surgical management and long-term follow-up of one patient.

A 24-year-old woman presented for treatment of her distorted facial appearance. She showed marked widening of the face and skull, which had first become noticeable in childhood. Significant thickening of the cortical bone was seen radiographically throughout the skeleton. Routine laboratory and endocrinological tests showed normal results. These findings, together with a family history of bone disorder, led to the diagnosis of hyperostosis corticalis generalisata. The lower border of the mandible was resected, resulting in improved facial appearance. During the 8-year follow-up, no changes were seen with regard to the mandible.

Calvarial hyperostosis: a benign X-linked recessive disorder.

We report a family with what appears to be a unique X-linked recessive disorder of isolated hyperostosis of the calvarium. Although irregularity of the calvarium and exophytic prominences of the frontoparietal bones were apparent in infancy, premature cranial suture closure did not occur and there was no evidence of increased intracranial pressure despite a Luckenshadel appearance of the skull. Other membranous bones and the tubular bones were not involved. Calvarial bone biopsy from one patient showed vacuolated histiocytes suggesting a storage disease; however, neurologic deterioration, hepatosplenomegaly, and dysostosis multiplex did not occur. The affected family members had normal stature, normal occipitofrontal circumference, and no other medical problems. The biochemical basis of this disorder is not known. Although storage of abnormal material is possible, the long-term prognosis seems favorable.

Infantile cortical hyperostosis of the ribs (Caffey's disease) without mandibular involvement.

Infantile cortical hyperostosis (ICH), or Caffey's disease, first reported by Caffey and Silverman in 1945, is a benign condition characterized radiographically by corticoperiosteal thickening of bone with subperiosteal new bone formation. Sites of occurrence vary, with the mandible being involved in 75%-80% of cases. The following is a case report of ICH limited to four contiguous ribs with no evidence of mandibular involvement.

Two cases of Van Buchem's disease.

A brother and sister suffering from hyperostosis corticalis generalisata familiaris (van Buchem's disease) are described. Both presented in early adult life with signs and symptoms of raised intracranial pressure and underwent partial craniectomy. Following surgery normal intellectual function was maintained and both survived to old age. In later life one showed cerebellar deficit due to bony encroachment of the posterior cranial fossa, while the other had a spastic paraparesis due to spinal cord compression. Several other siblings were affected by this disease which appears to be transmitted as an autosomal recessive gene.