ESPE Abstracts (2016) 86 P-P1-605

A New Case of Intragenic Deletion in IGF1R with Very Mild Phenotype

Ruggero Coppola, Caterina Luongo, Raffaella Nacca, Marcella Sasso, Anna Grandone, Emanuele Miraglia del Giudice & Laura Perrone


Dipartimento della Donna, del Bambino e di Chirurigia Generale e Specialistica, Seconda Università degli Studi di Napoli, Naples, Italy


Background: IGF1R mutations are characterized by IGF-1 resistance causing impaired fetal and postnatal growth. Several reports in children with heterozygous defects of IGF1R have demonstrated a variable phenotype, which can be associated to microcephaly, dismorphic features and mild developmental delay.

Case presentation: We report of an 8-years-old boy, who came at our observation with short stature (−3.2 SDS) and mild microcephaly. He was born SGA and familial medical history revealed short stature in both parents (target height −2.4 SDS). Psychomotor development was normal. His bone age evaluated by TW2 method was 6 years. His laboratory data excluded a GH deficiency and his IGF1 levels were normal. GH treatment (0.035 mg/Kg per die) was started, but it was interrupted after 1 year of therapy because of elevated IGF-1 levels (>95 th) and no clinical response (−3.1 SDS). Genetic analysis of IGF1R revealed an heterozygous deletion of exon 3; the same deletion was found in the father (adult height −2.2 SDS) and in one of the two sisters (born SGA; height −2 SDS; head circumference −2 SDS) of the index case. Both affected relatives had normal psychomotor development. Our patient started GH treatment again at a higher dosage (0.040 mg/kg per die), with good response.

Conclusions: We expand the phenotypic knowledge of intragenic deletions of IGF1R reporting a family with deletion of exon 3, determining a milder phenotype without mental retardation, psychiatric features and dysmorphisms. In fact, only a family with exon 3 deletion has been previously described and dismorphic features, psychiatric phenotypes and mental delay were present in all affected members. The explanation of these differences warrant further investigation. Moreover we confirm the importance of IGF1R analysis in SGA patients with short stature and microcephaly poor responsive to GH treatment.

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