Hyperphosphatemic familial tumoral calcinosis caused by a novel variant in the GALNT3 gene.

AIM: Hyperphosphatemic familial tumoral calcinosis (HFTC) is a rare endocrine disorder caused by autosomal recessive variants in GALNT3, FGF23, and KL leading to progressive calcification of soft tissues and subsequent clinical effects. The aim of this was to study the cause of HFTC in an Iranian family. PATIENTS AND METHODS: Four generations of a family with HFTC were studied for understanding the genetic pattern of the disease. Whole exome sequencing was applied on genomic DNA of the proband. Based on its result, genetically altered sequences were checked in his family through sanger sequencing. Then bioinformatics approaches as well as co-segregation analysis were applied to validate the genetic alteration. RESULTS: A novel homozygous variant in exon four of GALNT3, namely p.R261Q was found. The parents and sister were carriers. CONCLUSION: To our knowledge, it is the first-reported Iranian family with GALNT3-CDG novel variant.

[Caffey disease. A case report]. / Enfermedad de caffey. Reporte de un caso.

Infantile cortical hyperostosis or Caffey-Silverman syndrome is a disorder of unknown cause that affects the skeleton and some of the contiguous fascias and muscles. It occurs under all circumstances, in cities, rural communities, in all types of climates, seasons, races, social strata, and its incidence is the same among males and females. We report herein a very rare disease, little known in world literature, in order to disseminate within the orthopedic setting the musculoskeletal alterations we found in Caffey-Silverman disease. We report a seven year-old female patient diagnosed with Caffey-Silverman disease, with presence of its different manifestations that include swelling of the right forearm (indurated edema without phlogosis), pain, irritability with a chronicity involving a course of years. She is undergoing primary treatment consisting of observation and symptom relief. We know that it is a disorder with an unknown etiology. We also know there is hypoxia, local necrosis and periosteal reaction; however, the triggers of these changes are still a mystery. There are several hypotheses, but none of them has been proven. Some reports of familial occurrence suggest a possible hereditary factor. The natural self-limitation of this disease has made it difficult to establish the type of heredity; it is likely a trait with an autosomal dominant transmission with variable penetrance. A hereditary defect of periosteal arterioles has been propose as well as factors such as diet, an allergic base and an immune origin. Attempts have been made to isolate viruses and bacteria, but they have failed. Serologic infection tests have been negative. Caffey syndrome is little known in world literature, as there are only a few articles on it in the PUBMED, EMBASE, MEDIGRAPHIC, LILACS and ARTEMISA data bases. Being aware of this rare disease allows for early suspicion and a better workup and contributes to orthopedic knowledge as its musculoskeletal alterations are reported. Despite its low prevalence, it should be part of the differential diagnoses in children with soft tissue swelling and bone abnormalities with signs of irritability and fever.

A 2-month-old infant with acute swelling of the extremities and mandible.

The following case is presented to illustrate the roentgenographic and clinical findings of a condition of interest to the orthopedic surgeon. The initial history, physical findings, and roentgenographic examinations are found on the first two pages. The clinical and roentgenographic diagnoses are presented on the following pages.

Severe prenatal infantile cortical hyperostosis (Caffey's disease).

We describe three cases of prenatal infantile cortical hyperostosis (Caffey's disease) from two families, all associated with maternal polyhydramnios. Case 1 (family 1) was an early early neonatal death after delivery at 27 weeks gestation, case 2 (family 2) an intrauterine death at 33 weeks. Case 3 (family 2) had limited skeletal involvement and followed a course typical for Caffey's disease. Only six cases of prenatal Caffey's disease with extensive skeletal involvement have previously been described. Polyhydramnios was reported in all but one and the condition was lethal unless pregnancy reached term. To our knowledge cases 2 and 3 reported here represent the first description of Caffey's disease in which the prenatal lethal form was not sporadic.

Sporadic congenital Caffey's disease.

Caffey's disease is an inflammatory skeletal disorder of infancy manifested clinically by fever, soft-tissue swelling, and constitutional signs with radiographic evidence of periosteal new bone formation. Although prevalent between 1940 and 1960, nonfamilial cases have become extraordinarily rare. The authors report the sporadic occurrence of congenital Caffey's disease in a premature infant and note an interesting association with maternal herpes zoster early during gestation. The etiology of this mysterious disease is likely to remain elusive as new cases become scarce.

Different clinical picture in early and late onset cortical hyperostosis.

Six cases of Cortical Hyperostosis (C.H.) are presented. The clinical and laboratory features of the disease seem to be related to age at onset. In fact, our cases with a later onset (after the first year of life) are characterized by: a) a longer duration of the disease and a particularly high frequency of relapses; b) the absence of any sign of mandibular involvement; c) the presence of eosinophilia (700-1300/mm3). In two out of three cases having a later onset clinical and laboratory data suggest the hypotesis of a immunoallergic pathogenesis and particularly of cow's milk allergy. A review of the literature appears to confirm the differences between early and late onset forms of C.H. as for as the sites of skeletal involvement and the whole clinical course are concerned.

The Kenny-Caffey syndrome: growth retardation and hypocalcemia in a young boy.

A 2-year-old black boy with the Kenny-Caffey syndrome was first evaluated because of growth retardation and hypocalcemia. Hypothalamic-pituitary function was normal. Basal serum somatomedin C levels were normal for age, but did not increase during short-term administration of human growth hormone. Serum immunoreactive parathyroid hormone levels remained inappropriately low during spontaneous and induced hypocalcemia, indicating that hypocalcemia was the consequence of hypoparathyroidism. The manifestations of 15 patients with this syndrome are tabulated.