Neonatal lethal Costello syndrome and unusual dinucleotide deletion/insertion mutations in HRAS predicting p.Gly12Val.
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.
Affiliation: Genetic Medicine, Manchester Academic Health Science Centre, University of Manchester and Central Manchester University Hospitals NHS Foundation Trust, Manchester, UK.Show MeSH
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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.
Affiliation: Genetic Medicine, Manchester Academic Health Science Centre, University of Manchester and Central Manchester University Hospitals NHS Foundation Trust, Manchester, UK.