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Neonatal lethal Costello syndrome and unusual dinucleotide deletion/insertion mutations in HRAS predicting p.Gly12Val.

Burkitt-Wright EM, Bradley L, Shorto J, McConnell VP, Gannon C, Firth HV, Park SM, D'Amore A, Munyard PF, Turnpenny PD, Charlton A, Wilson M, Kerr B - Am. J. Med. Genet. A (2012)

Bottom Line: Dysmorphism was subtle or non-specific, with edema, coarsened facial features, prominent forehead, depressed nasal bridge, anteverted nares, and low-set ears.Proximal upper limb shortening, a small bell-shaped chest, talipes, and fixed flexion deformities of the wrists were seen.Clinical management should be informed by knowledge of the poor prognosis of this condition.

View Article: PubMed Central - PubMed

Affiliation: Genetic Medicine, Manchester Academic Health Science Centre, University of Manchester and Central Manchester University Hospitals NHS Foundation Trust, Manchester, UK.

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Related in: MedlinePlus

Postmortem anatomy and histology. a: Macroscopic appearance of coronal section through the heart, showing hypertrophic cardiomyopathy, with particularly marked septal hypertrophy. b,c: View into chest and abdominal cavity. Note generalized pallor of muscles and thickening of diaphragm. d: Delayed lung development for 35 weeks' gestation (adjusted), similar to canalicular phase, is shown. The pulmonary artery and bronchiole travel together (left), and the pulmonary vein (right) is normally positioned in the interlobular septum. Hematoxylin and eosin stain, original magnification 200×. e: Cytokeratin (brown chromogen) marks the alveolar lining cells, demonstrating an excess of stroma and too little airspace. Cytokeratin AE1/3 immunoperoxidase, hematoxylin counterstain, original magnification 200×. f: CD34 (brown chromogen) marks the capillaries. Capillary apposition and density is not decreased. CD34 immunoperoxidase, hematoxylin counterstain, original magnification 400×.
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fig02: Postmortem anatomy and histology. a: Macroscopic appearance of coronal section through the heart, showing hypertrophic cardiomyopathy, with particularly marked septal hypertrophy. b,c: View into chest and abdominal cavity. Note generalized pallor of muscles and thickening of diaphragm. d: Delayed lung development for 35 weeks' gestation (adjusted), similar to canalicular phase, is shown. The pulmonary artery and bronchiole travel together (left), and the pulmonary vein (right) is normally positioned in the interlobular septum. Hematoxylin and eosin stain, original magnification 200×. e: Cytokeratin (brown chromogen) marks the alveolar lining cells, demonstrating an excess of stroma and too little airspace. Cytokeratin AE1/3 immunoperoxidase, hematoxylin counterstain, original magnification 200×. f: CD34 (brown chromogen) marks the capillaries. Capillary apposition and density is not decreased. CD34 immunoperoxidase, hematoxylin counterstain, original magnification 400×.

Mentions: Postmortem examination revealed length and head circumference on the 25th centile, but weight below the 9th, despite apparent excessive subcutaneous tissue of the limbs, face, and neck. Heart weight was 34 g (expected: 20 g), biventricular and septal hypertrophy (Fig. 2a) with mild interstitial edema were present, but no fibrosis or myofibrillar disarray. Other muscles were firm and bulky, especially the diaphragm (Fig. 2b,c). Evidence of bronchopneumonia and healing bronchopulmonary dysplasia confirmed the cause of death. The pancreas showed increased islet cell size and number, whilst the thymus was small and atrophic. Immature cryptorchid testes were well above the pelvic rim. The brain appeared structurally normal, but weighed 602 g (expected: 413 g). Radiographs and the rest of the internal examination were normal, with no further histological abnormalities evident. The diagnosis of CS was only established some time after the baby's death, when he was presented at an international dysmorphology meeting.


Neonatal lethal Costello syndrome and unusual dinucleotide deletion/insertion mutations in HRAS predicting p.Gly12Val.

Burkitt-Wright EM, Bradley L, Shorto J, McConnell VP, Gannon C, Firth HV, Park SM, D'Amore A, Munyard PF, Turnpenny PD, Charlton A, Wilson M, Kerr B - Am. J. Med. Genet. A (2012)

Postmortem anatomy and histology. a: Macroscopic appearance of coronal section through the heart, showing hypertrophic cardiomyopathy, with particularly marked septal hypertrophy. b,c: View into chest and abdominal cavity. Note generalized pallor of muscles and thickening of diaphragm. d: Delayed lung development for 35 weeks' gestation (adjusted), similar to canalicular phase, is shown. The pulmonary artery and bronchiole travel together (left), and the pulmonary vein (right) is normally positioned in the interlobular septum. Hematoxylin and eosin stain, original magnification 200×. e: Cytokeratin (brown chromogen) marks the alveolar lining cells, demonstrating an excess of stroma and too little airspace. Cytokeratin AE1/3 immunoperoxidase, hematoxylin counterstain, original magnification 200×. f: CD34 (brown chromogen) marks the capillaries. Capillary apposition and density is not decreased. CD34 immunoperoxidase, hematoxylin counterstain, original magnification 400×.
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Related In: Results  -  Collection

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fig02: Postmortem anatomy and histology. a: Macroscopic appearance of coronal section through the heart, showing hypertrophic cardiomyopathy, with particularly marked septal hypertrophy. b,c: View into chest and abdominal cavity. Note generalized pallor of muscles and thickening of diaphragm. d: Delayed lung development for 35 weeks' gestation (adjusted), similar to canalicular phase, is shown. The pulmonary artery and bronchiole travel together (left), and the pulmonary vein (right) is normally positioned in the interlobular septum. Hematoxylin and eosin stain, original magnification 200×. e: Cytokeratin (brown chromogen) marks the alveolar lining cells, demonstrating an excess of stroma and too little airspace. Cytokeratin AE1/3 immunoperoxidase, hematoxylin counterstain, original magnification 200×. f: CD34 (brown chromogen) marks the capillaries. Capillary apposition and density is not decreased. CD34 immunoperoxidase, hematoxylin counterstain, original magnification 400×.
Mentions: Postmortem examination revealed length and head circumference on the 25th centile, but weight below the 9th, despite apparent excessive subcutaneous tissue of the limbs, face, and neck. Heart weight was 34 g (expected: 20 g), biventricular and septal hypertrophy (Fig. 2a) with mild interstitial edema were present, but no fibrosis or myofibrillar disarray. Other muscles were firm and bulky, especially the diaphragm (Fig. 2b,c). Evidence of bronchopneumonia and healing bronchopulmonary dysplasia confirmed the cause of death. The pancreas showed increased islet cell size and number, whilst the thymus was small and atrophic. Immature cryptorchid testes were well above the pelvic rim. The brain appeared structurally normal, but weighed 602 g (expected: 413 g). Radiographs and the rest of the internal examination were normal, with no further histological abnormalities evident. The diagnosis of CS was only established some time after the baby's death, when he was presented at an international dysmorphology meeting.

Bottom Line: Dysmorphism was subtle or non-specific, with edema, coarsened facial features, prominent forehead, depressed nasal bridge, anteverted nares, and low-set ears.Proximal upper limb shortening, a small bell-shaped chest, talipes, and fixed flexion deformities of the wrists were seen.Clinical management should be informed by knowledge of the poor prognosis of this condition.

View Article: PubMed Central - PubMed

Affiliation: Genetic Medicine, Manchester Academic Health Science Centre, University of Manchester and Central Manchester University Hospitals NHS Foundation Trust, Manchester, UK.

Show MeSH
Related in: MedlinePlus