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Multiple endocrine neoplasias type 2B and RET proto-oncogene.

Martucciello G, Lerone M, Bricco L, Tonini GP, Lombardi L, Del Rossi CG, Bernasconi S - Ital J Pediatr (2012)

Bottom Line: The 95% of MEN 2B patients are associated with a point mutation in exon 16 (M918/T).A second point mutation at codon 883 has been found in 2%-3% of MEN 2B cases.When possible, this intervention should be performed with prophylactic aim before 1 year of age in patients with molecular genetic diagnosis.

View Article: PubMed Central - HTML - PubMed

Affiliation: University of Genova, DIPE, Via Gaslini, 5 Genova (16147), Italy. martucciello@yahoo.com

ABSTRACT
Multiple Endocrine Neoplasia type 2B (MEN 2B) is an autosomal dominant complex oncologic neurocristopathy including medullary thyroid carcinoma, pheochromocytoma, gastrointestinal disorders, marphanoid face, and mucosal multiple ganglioneuromas. Medullary thyroid carcinoma is the major cause of mortality in MEN 2B syndrome, and it often appears during the first years of life. RET proto-oncogene germline activating mutations are causative for MEN 2B. The 95% of MEN 2B patients are associated with a point mutation in exon 16 (M918/T). A second point mutation at codon 883 has been found in 2%-3% of MEN 2B cases. RET proto-oncogene is also involved in different neoplastic and not neoplastic neurocristopathies. Other RET mutations cause MEN 2A syndrome, familial medullary thyroid carcinoma, or Hirschsprung's disease. RET gene expression is also involved in Neuroblastoma. The main diagnosis standards are the acetylcholinesterase study of rectal mucosa and the molecular analysis of RET. In our protocol the rectal biopsy is, therefore, the first approach. RET mutation detection offers the possibility to diagnose MEN 2B predisposition at a pre-clinical stage in familial cases, and to perform an early total prophylactic thyroidectomy. The surgical treatment of MEN 2B is total thyroidectomy with cervical limphadenectomy of the central compartment of the neck. When possible, this intervention should be performed with prophylactic aim before 1 year of age in patients with molecular genetic diagnosis. Recent advances into the mechanisms of RET proto-oncogene signaling and pathways of RET signal transduction in the development of MEN 2 and MTC will allow new treatment possibilities.

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The first toe is longer than the others and there is a wide space between the first and second toe.
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Figure 3: The first toe is longer than the others and there is a wide space between the first and second toe.

Mentions: Although skeletal abnormalities may not be pronounced in the first few years, they can be considered one of the key to early diagnosis for the physician. A tall stature with disproportionately long limbs and digits, a long and narrow face with deep-set eyes, and a high, narrow palate are often combined with joint hypermobility and pectus deformities. Chest deformities such as pectus escavatum or carinatum are related to an overgrowth of the ribs, pushing the sternum outward or inward. Scoliosis is common in MEN 2B and the frequency is higher in adults. Untreated, significant spinal deformity can lead to chronic back pain and restrictive lung disease. There is a correlation between scoliosis and back pain, which occurs with greater frequency in adults with MEN2B than in the general population. Joint laxity can be pronounced in young children and may lead to delayed gross motor development. Joint dislocation is a rare occurrence. Mild contractures of elbows, knees, or toes are present in a small fraction of children and adults. The first toe is longer than the others and there is a wide space between the first and second toe (Figure 3). Adults often have an asthenic body habitus, and crowding of the teeth because of maxilla and mandible are narrowing.


Multiple endocrine neoplasias type 2B and RET proto-oncogene.

Martucciello G, Lerone M, Bricco L, Tonini GP, Lombardi L, Del Rossi CG, Bernasconi S - Ital J Pediatr (2012)

The first toe is longer than the others and there is a wide space between the first and second toe.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3368781&req=5

Figure 3: The first toe is longer than the others and there is a wide space between the first and second toe.
Mentions: Although skeletal abnormalities may not be pronounced in the first few years, they can be considered one of the key to early diagnosis for the physician. A tall stature with disproportionately long limbs and digits, a long and narrow face with deep-set eyes, and a high, narrow palate are often combined with joint hypermobility and pectus deformities. Chest deformities such as pectus escavatum or carinatum are related to an overgrowth of the ribs, pushing the sternum outward or inward. Scoliosis is common in MEN 2B and the frequency is higher in adults. Untreated, significant spinal deformity can lead to chronic back pain and restrictive lung disease. There is a correlation between scoliosis and back pain, which occurs with greater frequency in adults with MEN2B than in the general population. Joint laxity can be pronounced in young children and may lead to delayed gross motor development. Joint dislocation is a rare occurrence. Mild contractures of elbows, knees, or toes are present in a small fraction of children and adults. The first toe is longer than the others and there is a wide space between the first and second toe (Figure 3). Adults often have an asthenic body habitus, and crowding of the teeth because of maxilla and mandible are narrowing.

Bottom Line: The 95% of MEN 2B patients are associated with a point mutation in exon 16 (M918/T).A second point mutation at codon 883 has been found in 2%-3% of MEN 2B cases.When possible, this intervention should be performed with prophylactic aim before 1 year of age in patients with molecular genetic diagnosis.

View Article: PubMed Central - HTML - PubMed

Affiliation: University of Genova, DIPE, Via Gaslini, 5 Genova (16147), Italy. martucciello@yahoo.com

ABSTRACT
Multiple Endocrine Neoplasia type 2B (MEN 2B) is an autosomal dominant complex oncologic neurocristopathy including medullary thyroid carcinoma, pheochromocytoma, gastrointestinal disorders, marphanoid face, and mucosal multiple ganglioneuromas. Medullary thyroid carcinoma is the major cause of mortality in MEN 2B syndrome, and it often appears during the first years of life. RET proto-oncogene germline activating mutations are causative for MEN 2B. The 95% of MEN 2B patients are associated with a point mutation in exon 16 (M918/T). A second point mutation at codon 883 has been found in 2%-3% of MEN 2B cases. RET proto-oncogene is also involved in different neoplastic and not neoplastic neurocristopathies. Other RET mutations cause MEN 2A syndrome, familial medullary thyroid carcinoma, or Hirschsprung's disease. RET gene expression is also involved in Neuroblastoma. The main diagnosis standards are the acetylcholinesterase study of rectal mucosa and the molecular analysis of RET. In our protocol the rectal biopsy is, therefore, the first approach. RET mutation detection offers the possibility to diagnose MEN 2B predisposition at a pre-clinical stage in familial cases, and to perform an early total prophylactic thyroidectomy. The surgical treatment of MEN 2B is total thyroidectomy with cervical limphadenectomy of the central compartment of the neck. When possible, this intervention should be performed with prophylactic aim before 1 year of age in patients with molecular genetic diagnosis. Recent advances into the mechanisms of RET proto-oncogene signaling and pathways of RET signal transduction in the development of MEN 2 and MTC will allow new treatment possibilities.

Show MeSH
Related in: MedlinePlus