Splice site mutations in GH1 detected in previously (Genetically) undiagnosed families with congenital isolated growth hormone deficiency type II.

BACKGROUND: Congenital isolated growth hormone deficiency (IGHD) is a rare endocrine disorder that presents with severe proportionate growth failure. Dominant (type II) IGHD is usually caused by heterozygous mutations of GH1. The presentation of newly affected family members in 3 families with dominant IGHD in whom previous genetic testing had not demonstrated a GH1 mutation or had not been performed, prompted us to identify the underlying genetic cause. METHODS: GH1 was sequenced in 3 Caucasian families with a clinical autosomal dominant IGHD. RESULTS: All affected family members had severe growth hormone (GH) deficiency that became apparent in the first 2 years of life. GH treatment led to a marked increase in height SDS. So far, no other pituitary dysfunctions have become apparent. In the first family a novel splice site mutation in GH1 was identified (c.172-1G>C, IVS2-1G>C). In two other families a previously reported splice site mutation (c.291+1G>A, IVS3+1G>A) was found. CONCLUSION: These data show that several years after negative genetic testing it was now possible to make a genetic diagnosis in these families with a well-defined, clearly heritable, autosomal dominant IGHD. This underscores the importance of clinical and genetic follow-up in a multidisciplinary setting. It also shows that even without a positive family history, genetic testing should be considered if the phenotype is strongly suggestive for a genetic syndrome. Identification of pathogenic mutations, like these GH1 mutations, has important clinical implications for the surveillance and genetic counseling of patients and expands our knowledge on the genotype-phenotype correlation.

[Psychosocial deprivation as a cause of growth retardation in children]. / Psychosociale deprivatie als oorzaak van groeivertraging bij kinderen.

Patient A, a 3-year-old boy with short stature, in whom a partial growth hormone deficiency had been diagnosed, was treated with growth hormone. Further evaluation, however, showed that there was evidence of psychosocial deprivation as a result of an unstable family situation. After psychosocial circumstances improved, growth hormone therapy was discontinued, following which no further growth retardation was observed. In the case of patient B, a 10-year-old girl with short stature, reconstruction of the growth curve showed that growth stagnation had occurred around the age of 6 years. The cause was psychosocial deprivation during a severe illness in one of her triplet sisters. Following stagnation, there was insufficient compensatory growth, resulting in short stature. These cases emphasize the importance of reconstruction of the growth curve and of taking a thorough psychosocial case history in all children with growth retardation or small stature. The clinical picture of psychosocial growth retardation can be similar to the picture of idiopathic, isolated growth hormone deficiency. Prompt and accurate diagnosis prevents unnecessary, extensive investigations and enables adequate treatment and support.