A novel NKX3-2 mutation associated with perinatal lethal phenotype of spondylo-megaepiphyseal-metaphyseal dysplasia in a neonate
| Autor: | Mehmet Alikasifoglu, Gen Nishimura, Tutku Soyer, Gülen Eda Utine, Pelin Ozlem Simsek-Kiper, Koray Boduroğlu, Can Kosukcu, Özlem Akgün-Doğan, Rahsan Gocmen, Ayse Korkmaz-Toygar |
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| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Male Pediatrics medicine.medical_specialty Skeletal survey 030105 genetics & heredity Osteochondrodysplasias Short stature Duodenal atresia 03 medical and health sciences Fatal Outcome Genetics medicine Humans Genetics (clinical) Homeodomain Proteins business.industry Ossification Infant Newborn General Medicine Cervical cord compression medicine.disease Trunk 030104 developmental biology Phenotype Respiratory failure Dysplasia Mutation medicine.symptom business Transcription Factors |
| Zdroj: | European journal of medical genetics. 62(1) |
| ISSN: | 1878-0849 |
| Popis: | Spondylo-megaepiphyseal-metaphyseal dysplasia (SMMD) is an autosomal recessive skeletal dysplasia, characterized by disproportionate short stature with a short and stiff neck and trunk. SMMD is caused by inactivating mutations in NKX3-2, which encodes a homeobox-containing protein. Because of the rarity of the disorder, the diagnostic feature has not been fully established yet. We describe an affected newborn with dysmorphic facial features and severe short trunk. The patient required immediate intubation at the delivery room and duodenal atresia was detected during his course in neonatal intensive care unit. Skeletal survey revealed total absence of the ossification of the vertebral bodies, pubis, and ischia. Mainly the femora was short and broad with mild flaring of the metaphyses. The downward sloping or tented appearance of the ribs was distinctive. A diagnosis of SMMD was made on clinical and radiological grounds. Molecular analysis revealed homozygosity for a novel mutation, c.507-508delCA (p.Gly171Cysfs*55) in exon 2 of NKX3-2. The patient was operated on postnatal day 7 for duodenal atresia. In the post-operative period he developed sepsis and respiratory failure and he died on postnatal day 14. Although no neuroradiologic imaging could be performed, the findings of clubfoot, neuromuscular respiratory insufficiency requiring invasive mechanical ventilation and downward sloping or tented appearance of the ribs were suggestive of very early cervical cord compression leading to perinatal mortality. To our knowledge this patient yet represents one of the most severe postnatal phenotypes of SMMD. |
| Databáze: | OpenAIRE |
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