Growth Hormone Deficiency in MCAP: An Association with Activating Mutations in PIK3CA
Megalencephaly-capillary malformation syndrome (MCAP) is an overgrowth disorder characterized by cerebrocortical malformations, vascular anomalies, and segmental overgrowth secondary to somatic activating mutations in the PI3K-AKT-MTOR pathway ( PIK3CA ). Cases of growth failure and hypoglycemia hav...
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Veröffentlicht in: | American journal of medical genetics. Part A 2019-11, Vol.182 (1), p.162-168 |
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Format: | Artikel |
Sprache: | eng |
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Zusammenfassung: | Megalencephaly-capillary malformation syndrome (MCAP) is an overgrowth disorder characterized by cerebrocortical malformations, vascular anomalies, and segmental overgrowth secondary to somatic activating mutations in the PI3K-AKT-MTOR pathway (
PIK3CA
). Cases of growth failure and hypoglycemia have been reported in patients with MCAP, raising the suspicion for unappreciated growth hormone (GH) deficiency. Here we report an observational multi-center study of children with MCAP and GH deficiency. Eleven participants were confirmed to have GH deficiency, all with very low or undetectable circulating concentrations of insulin-like growth factor-1 and insulin-like growth factor binding protein-3. Seven underwent GH stimulation testing and all had insufficient responses with a median GH peak of 3.7 ng/ml (range 1.1-8.6). Growth patterns revealed a drastic decline in length z-scores within the first year of life but then stabilized afterward. Five were treated with GH; one discontinued due to inconsolability. The other four participants continued on GH with improvement in linear growth velocity. Other endocrinopathies were identified in seven of the 11 participants in this cohort. This study indicates that GH deficiency is associated with MCAP and that children with MCAP and hypoglycemia and/or postnatal growth failure should be evaluated for GH deficiency and other endocrinopathies. |
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ISSN: | 1552-4825 1552-4833 |
DOI: | 10.1002/ajmg.a.61403 |