Clinical and Laboratory Characteristics of a Large Iranian Kindred Afflicted with Von Hippel Lindau Disease.

BACKGROUND: Von Hippel Lindau (VHL) disease is a hereditary disorder characterized by the development of benign or malignant tumors in the brain, spinal cord, eyes, adrenal medulla, kidney, pancreas, and many other organs. Advances in molecular diagnosis have led to the identification of the affected members of families at earlier stages. We present the clinical, laboratory, and genetic characteristics of five generations of a large Iranian kindred with VHL. METHODS: The proband, a 52-year-old Iranian man, was recognized with VHL. All family members underwent clinical, laboratory, imaging, and genetic evaluation. Medical files and histopathology reports of patients who had been operated on before were also reviewed. Diagnosis of the disease was based on clinical findings, positive family history of VHL, and development of a central nervous system or retinal hemangioblastoma or pheochromocytoma. RESULTS: Based on diagnostic criteria, our initial evaluations revealed that 10 members of the family had already been affected by the disease. Among them, nine had pheochromocytoma, and one had retinal hemangioblastoma. There was no case of kidney tumors among the kindred. CONCLUSIONS: Study results show the high penetrance of the disease and focus on the large burden imposed by the disease on the health and quality of life of patients afflicted with the disease, emphasizing the importance of surveillance from early childhood for detection and management of the disease as early as possible.

Multiple endocrine neoplasia type 2A in an Iranian family: clinical and genetic studies.

Multiple endocrine neoplasia (MEN) type 2A, a dominant inherited syndrome caused by germline activating mutations in the RET protooncogene, is characterized by association of medullary thyroid carcinoma, pheochromocytoma and primary hyperparathyroidism. There is limited data on this disease in the Middle East region. In this paper, we present clinical and genetic studies of an Iranian patient and her family members. The patient was a 49-year old Iranian woman who presented with hypertension due to bilateral pheochromocytoma. She had history of a medullary carcinoma of thyroid which had been operated 28 years ago. Analysis of the RET gene in the family revealed a C634R mutation in codon 11 and 3 polymorphisms, G691S, S836S and S904S in codons 11, 14 and 15, respectively, that might have been important in modifying the clinical picture. Due to paucity of information on MEN type 2 in the area, this study can be helpful in portraying the clinical and cytogenetic characteristics of the disease in the region.

Intrauterine diagnosis and management of fetal goitrous hypothyroidism: a report of an Iranian family with three consecutive pregnancies complicated by fetal goiter.

The diagnosis and treatment of hypothyroidism during the fetal period may decrease perinatal morbidity and are believed to be important to optimize growth and intellectual development. Herewith a case report of fetal goitrous hypothyroidism is presented in a euthyroid mother, detected at 34 weeks' gestation by ultrasonography, and treated with intra-amniotic levothyroxine injections. The mother had two previous consecutive pregnancies (13 and 8 years ago), also complicated by the occurrence of fetal goiter, resulting in tracheal compression, asphyxia, and early neonatal death in the first and in an emergency cesarean section delivery, because of fetal malpresentation, in the second neonate affected by congenital hypothyroidism (CH). The present male newborn, although born without observable goiter, had a large thyroid on ultrasonography and an early rise of his peripheral venous blood thyrotropin confirmed the diagnosis of CH. Low serum thyroglobulin in the proband and his older brother and parental consanguinity was mostly compatible with a thyroglobulin defective synthesis and secretion as the cause of CH and fetal goiter. Despite apparently sufficient dose of intraamniotic levothyroxine injections repeated weekly from 34-37 weeks' gestation (i.e., four injections of 500 microg levothyroxine), neonatal bone age on the second day of life showed delayed skeletal maturation.