RESUMEN
Congenital growth hormone deficiency is a rare disorder with an incidence of approximately 1 in 4,000 live births. Pituitary development is under the control of a multitude of spatiotemporally regulated signaling molecules and transcription factors. Mutations in the genes encoding these molecules can result in hypopituitarism but for the majority of children with congenital hypopituitarism, the aetiology of their disease remains unknown. The proband is a 5-year-old girl who presented with neonatal hypoglycaemia and prolonged jaundice. No definitive endocrine cause of hypoglycaemia was identified in the neonatal period. She was born of normal size at 42 weeks but demonstrated growth failure with a progressive reduction in height to -3.2 SD by age 4.5 years and failed a growth hormone stimulation test with a peak growth hormone of 4.2 mcg/L. MRI of the pituitary gland demonstrated a hypoplastic anterior lobe and ectopic posterior lobe. Array CGH demonstrated an inherited 0.2 Mb gain at 1q21.1 and a de novo 4.8 Mb heterozygous deletion at 20p12.2-3. The deletion contained 17 protein coding genes including PROKR2 and BMP2, both of which are expressed during embryological development of the pituitary gland. PROKR2 mutations have been associated with hypopituitarism but a heterozygous deletion of this gene with hypopituitarism is a novel observation. In conclusion, congenital hypopituitarism can be present in individuals with a 20p12.3 deletion, observed with incomplete penetrance. Array CGH may be a useful investigation in select cases of early onset growth hormone deficiency, and patients with deletions within this region should be evaluated for pituitary hormone deficiencies.
Asunto(s)
Proteína Morfogenética Ósea 2/genética , Enanismo Hipofisario/genética , Hipopituitarismo/genética , Microftalmía/genética , Receptores Acoplados a Proteínas G/genética , Receptores de Péptidos/genética , Preescolar , Deleción Cromosómica , Cromosomas Humanos Par 20/genética , Hibridación Genómica Comparativa , Enanismo Hipofisario/fisiopatología , Desarrollo Embrionario/genética , Femenino , Heterocigoto , Humanos , Hipopituitarismo/fisiopatología , Microftalmía/fisiopatología , Mutación , Hipófisis/anomalías , Hipófisis/crecimiento & desarrolloRESUMEN
Congenital hyperinsulinism causes profound hypoglycemia, which may persist or resolve spontaneously. Among 13 children with congenital hyperinsulinism, elevated incretin hormone concentrations were detected in 2 with atypical, persistent disease. We suggest that incretin biomarkers may identify these patients, and that elevated hormone levels may contribute to their pathophysiology.
Asunto(s)
Biomarcadores/sangre , Hiperinsulinismo Congénito/sangre , Incretinas/sangre , Canales KATP/genética , Preescolar , Hiperinsulinismo Congénito/genética , Humanos , Lactante , Recién Nacido , Mutación , Reino UnidoRESUMEN
Congenital Hyperinsulinism is a condition with a number of genetic causes, but for the majority of patients, the underlying aetiology is unknown. We present here a rational argument for the use of computational biology as a valuable resource for identifying new candidate genes which may cause disease and for understanding the complex mechanisms which define the pathophysiology of this rare disease.