1/28. Stimulatory guanine nucleotide binding protein subunit 1 mutation in two siblings with pseudohypoparathyroidism type 1a and mother with pseudopseudohypoparathyroidism.Pseudohypoparathyroidism (PHP) type la is characterized by multihormone resistance and a constellation of somatic features referred to as Albright hereditary osteodystrophy. Several mutations in the gene coding for the Gs alpha subunit (GNAS1) have been described. Clinical symptoms are heterogeneous and initially laboratory parameters may be normal. We identified a 4 base pair deletion within GNAS1 in two affected siblings with PHP type la and their mother with presumed pseudo PHP. The female proband was diagnosed after an episode of apnoea and seizures. The younger brother was asymptomatic during infancy and had normal plasma parameters. PHP was diagnosed at the age of 4.4 years. Regular check-ups of siblings in families with index cases are therefore important. Molecular genetic analyses or biochemical screening for stimulatory guanine nucleotide binding protein defects should be performed. CONCLUSION: Different symptoms may be seen in patients with the same mutation causing pseudohypoparathyroidism or pseudopseudohypoparathyroidism. Therefore, clinical and biochemical investigations should be performed in all family members with an index patient.- - - - - - - - - - ranking = 1keywords = pseudohypoparathyroidism (Clic here for more details about this article) |
2/28. Identification of two novel deletion mutations within the Gs alpha gene (GNAS1) in Albright hereditary osteodystrophy.Albright hereditary osteodystrophy (AHO) is a genetic disorder characterized by short stature, skeletal defects, and obesity. Within AHO kindreds, some affected family members have only the somatic features of AHO [pseudopseudohypoparathyroidism (PPHP)], whereas others have these features in association with resistance to multiple hormones that stimulate adenylyl cyclase within their target tissues [pseudohypoparathyroidism type Ia (PHP Ia)]. Affected members of most AHO kindreds (both those with PPHP and those with PHP Ia) have a partial deficiency of Gs alpha, the alpha-subunit of the G protein that couples receptors to adenylyl cyclase stimulation, and in a number of cases heterozygous loss of function mutations within the Gs alpha gene (GNAS1) have been identified. Using PCR with the attachment of a high melting domain (GC-clamp) and temperature gradient gel electrophoresis, two novel heterozygous frameshift mutations within GNAS1 were found in two AHO kindreds. In one kindred all affected members (both PHP Ia and PPHP) had a heterozygous 2-bp deletion in exon 8, whereas in the second kindred a heterozygous 2-bp deletion in exon 4 was identified in all affected members examined. In both cases the frameshift encoded a premature termination codon several codons downstream of the deletion. In the latter kindred affected members were previously shown to have decreased levels of GNAS1 messenger ribonucleic acid expression. These results further underscore the genetic heterogeneity of AHO and provides further evidence that PHP Ia and PPHP are two clinical presentations of a common genetic defect. Serial measurements of thyroid function in members of kindred 1 indicate that TSH resistance progresses with age and becomes more evident after the first year of life.- - - - - - - - - - ranking = 0.2keywords = pseudohypoparathyroidism (Clic here for more details about this article) |
3/28. Albright's hereditary osteodystrophy associated with cerebellar pilocytic astrocytoma: coincidence or genetic relationship?Albright's hereditary osteodystrophy (AHO) is a rare inherited disease characterized by skeletal abnormalities, short stature, and, in some cases, resistance to parathyroid hormone, resulting in pseudohypoparathyroidism (PHP). Heterozygous inactivating mutations of the GNAS1 gene are responsible for reduced activity of the alpha subunit of the Gs protein (G(Salpha)), a protein that mediates hormone signal transduction across cell membranes. G(salpha) is also known to have oncogenic potentials, leading to the development of human pituitary tumors and Leydig cell tumors. Here, we report the 1st case, a 3.5-year-old girl, with classic AHO phenotype and PHP type 1A associated with a cerebellar pilocytic astrocytoma. Coincidence or genetic relationships of both diseases are discussed according to molecular findings and current literature.- - - - - - - - - - ranking = 0.1keywords = pseudohypoparathyroidism (Clic here for more details about this article) |
4/28. Primary palpebral and orbital ossification in pseudo-pseudohypoparathyroidism.PURPOSE: To present a case of ossification of the eyelid, episclera and orbit in a patient with pseudo-pseudohypoparathyroidism (pPHP). methods: A 20-year-old woman diagnosed with pseudo-pseudohypoparathyroidism underwent clinical and histopathological examination of calcified plaques of the right eyelid and orbit. The patient presented with a round face, tousled short hair and retarded speech. She had been diagnosed with pPHP at 3 years of age. During her first decade, calcified plaques developed in the right eyelid and orbit. Gradually, she developed horizontal diplopia, pseudo-ptosis and periorbital pain. Vertical eye movements were reduced to 10 mm, although levator function remained intact. Computer tomography scans of the orbit showed three separate dense structures. Radiographic findings also showed bilateral shortening of the fourth metacarpus and a calcified subcutaneous plaque in the left thigh. The patient's blood status revealed an elevated level of thyroid stimulating hormone, but was otherwise normal. The patient was treated with eltroxin and shortly afterwards regained normal hair and normal speech function. RESULTS: The calcified structures were removed surgically and almost normal eye movements were re-established. Histological examination of the excised tissue demonstrated bone formation. CONCLUSION: This is the first reported case of ossification of the eyelid and orbit in a patient with pseudo-pseudohypoparathyroidism.- - - - - - - - - - ranking = 0.7keywords = pseudohypoparathyroidism (Clic here for more details about this article) |
5/28. Molecular delineation of deletions on 2q37.3 in three cases with an Albright hereditary osteodystrophy-like phenotype.A minority of the reported cases of terminal 2q37 deletion clinically resemble Albright hereditary osteodystrophy (AHO)/pseudopseudohypoparathyroidism and have only mild-to-moderate mental retardation. Our molecular and cytogenetic fluorescence in situ hybridization (FISH) findings on an additional three patients further reduce the size of the minimal critical region deleted in this syndrome to about 3 Mb. This region includes the G-protein-coupled receptor 35 (GPR35), glypican 1 (GPC1), and serine/threonine protein kinase 25 (STK25) genes on 2q37.3. We have further defined several polymorphic variants within the coding region and flanking regions of GPR35 gene, which could potentially be useful for rapid detection of GPR35 gene deletion. We postulate that the absence of GPR35 may, at least partly, account for the phenotypic resemblance to the AHO. We also believe that the deletion of GPR35 could be responsible for the entity brachydactyly mental retardation syndrome (OMIM #600430), which was coined based on the above minority of patients with terminal 2q37 deletion. We recommend that every patient with AHO phenotype should undergo 2q subtelomeric FISH screen and subsequently a molecular study on the GPR35 gene. GPC1 and/or STK25 haploinsufficiency may also contribute to the AHO-like phenotype.- - - - - - - - - - ranking = 0.1keywords = pseudohypoparathyroidism (Clic here for more details about this article) |
6/28. osteoma cutis as a presenting sign of pseudohypoparathyroidism.Four unrelated children with osteoma cutis and Albright hereditary osteodystrophy (pseudohypoparathyroidism and pseudopseudohypoparathyroidism) are described. All four patients were normocalcemic when they were first seen with cutaneous ossification. A diagnosis of Albright hereditary osteodystrophy was established on the basis of associated somatic features, radiographic abnormalities, and family history. Progression to pseudohypoparathyroidism was documented in two children who developed hypocalcemia at 2 and 3 years of age, respectively. Early recognition of the skin manifestations of this syndrome and careful follow-up are important to prevent the deleterious effects of hypocalcemia. osteoma cutis is a common sign of Albright hereditary osteodystrophy in infancy and childhood, and its significance should not be overlooked, even in the normocalcemic patient.- - - - - - - - - - ranking = 0.7keywords = pseudohypoparathyroidism (Clic here for more details about this article) |
7/28. pseudopseudohypoparathyroidism with recurrent polyneuropathy: an autopsy report with special reference to the peripheral nervous system.The clinical and pathological findings of a 21-year-old girl suffering from pseudopseudohypoparathyroidism (PPHP) with relapsing neuropathy are described. Episodic exacerbations were accompanied by intracranial hypertension and were relieved by the administration of corticosteroids. At autopsy, pathologic changes were almost restricted to the peripheral axons and showed distal dominant depletion of myelinated fibers without any active myelin breakdown or inflammatory changes. The neuropathy is thought to be similar to chronic inflammatory demyelinating polyradiculoneuropathy (CIDP); however, the relationship, if any, between PPHP and CIDP is unknown.- - - - - - - - - - ranking = 0.5keywords = pseudohypoparathyroidism (Clic here for more details about this article) |
8/28. Albright's hereditary osteodystrophy.Albright's hereditary osteodystrophy is a rare inherited metabolic disorder characterized by a typical phenotype. It may be associated with or without resistance to parathyroid hormone (pseudohypoparathyroidism). Both forms may co-exist in the same family. Pseudohypoparathyroidism Type 1 and Pseudo-pseudohypoparathyroidism occur as a consequence of reduced erythrocyte membrane coupled with Gs alpha activity. We report here the variable inheritance of hormone resistance in the presence of characteristic phenotype and reduced Gs alpha activity in the same family.- - - - - - - - - - ranking = 0.2keywords = pseudohypoparathyroidism (Clic here for more details about this article) |
9/28. pseudopseudohypoparathyroidism and spinal cord compression.A 42 year old Greek male with pseudo-pseudohypoparathyroidism presented with difficulty in walking and with lower limb weakness. His physical signs included short stature, thick neck, short fourth metacarpals and metatarsals, and a spastic paraparesis. serum calcium and phosphate and parathyroid concentrations were normal. myelography demonstrated compression of the cervical and lumbar cord in association with local bony abnormalities.- - - - - - - - - - ranking = 0.5keywords = pseudohypoparathyroidism (Clic here for more details about this article) |
10/28. Pseudohypoparathyroidism: a difficult diagnosis in early childhood.We have studied one adult and three children with pseudohypoparathyroidism and observed that the physical character of short metacarpal bones is not evident in the first 4-5 years of life, that hypocalcaemia and hyperphosphataemia may be absent in the first years of life, but that the renal unresponsiveness to parathyroid hormone can still be demonstrated. Our data confirm earlier observation that in evaluating the renal responsiveness to parathyroid hormone, urinary cyclic amp is a better parameter than urinary phosphorus. Thus in early childhood, it may be difficult to differentiate between a normal child, a child with pseudohypoparathyroidism and a child with pseudo-pseudohypoparathyroidism unless the renal parathyroid hormone responsiveness is studied.- - - - - - - - - - ranking = 0.3keywords = pseudohypoparathyroidism (Clic here for more details about this article) |
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