UO di Genetica Medica
UO di Genetica Medica
Graziani V.,UOC di Pediatria e Neonatologia |
Mainetti M.,UOC di Pediatria e Neonatologia |
Zucchini A.,Pediatria di Faenza |
Poli M.,Pediatra di Famiglia |
And 3 more authors.
Medico e Bambino | Year: 2015
The paper describes the case of an infant with neonatal hypoglycaemia, hemihyperplasia, and macroglossia and the diagnostic process that leads to the confirmation of Beckwith-Wiedemann syndrome (BWS). BWS is an overgrowth disorder caused by epimutations and mutations affecting two imprinted loci on chromosome 11p15. Its clinical features are heterogeneous including macroglossia, macrosomia, hemihyperplasia, abdominal wall defects, neonatal hypoglycaemia, other minor anomalies and increased risk of embrional tumours especially during the first decade of life. In some cases with genetic mosaicism the symptoms may be poorly significant and obesity could be the only clinical manifestation. The Authors emphasize the importance of molecular studies to confirm the diagnosis and of the application of tumour surveillance protocols to improve life outcome.
PubMed | Unita di Genetica Medica, U.O. di Genetica Medica, University of Naples Federico II, Telethon Institute of Genetics and Medicine and 2 more.
Type: | Journal: American journal of medical genetics. Part A | Year: 2016
Smith-Magenis syndrome (SMS) is a complex genetic disorder caused by interstitial 17p11.2 deletions encompassing multiple genes, including the retinoic acid induced 1 gene-RAI1-or mutations in RAI1 itself. The clinical spectrum includes developmental delay, cognitive impairment, and behavioral abnormalities, with distinctive physical features that become more evident with age. No patients have been reported to have had offspring. We here describe a girl with developmental delay, mainly compromising the speech area, and her mother with mild intellectual disabilities and minor dysmorphic features. Both had sleep disturbance and attention deficit disorder, but no other atypical behaviors have been reported. In both, CGH-array analysis detected a 15q13.3 interstitial duplication, encompassing CHRNA7. However, the same duplication has been observed in several, apparently healthy, maternal relatives. We, thus, performed a whole exome sequencing analysis, which detected a frameshift mutation in RAI1, de novo in the mother, and transmitted to her daughter. No other family members carried this mutation. This is the first report of an SMS patient having offspring. Our experience confirms the importance of searching for alternative causative genetic mechanisms in case of confounding/inconclusive findings such as a CGH-array result of uncertain significance. 2016 Wiley Periodicals, Inc.