The index patient is a 40 year old male with BPES (Blepharophimosis, Ptosis, Epicanthus inversus Syndrome) associated with isolated
growth hormone deficiency. BPES is a rare genetic disease occurring either sporadically or as an autosomal dominant disorder. There are two phenotypes; in type 1, eyelid abnormalities are associated with ovarian failure and in type 2 eyelid abnormalities
only. The genes for both types have been mapped to Chromosome 3q23. Recently FOXL2 which is a winged helix / forkhead transcription factor gene has been cloned. FOXL2 is mutated to produce truncated proteins in type 1 families and larger proteins in type 2. FOXL2 is selectively expressed in eyelids and in the ovaries. There is however evidence of a low level of expression in the developing pituitary. (Crisponi et al Nature Genetics. 27: 159;
2001). We report two patients with BPES, father and daughter; Father (index patient) has isolated growth hormone deficiency of
childhood onset. He was always noted to be small since early childhood but was referred for investigation only at the age of 14 when he was minus 3.3 standard deviation scores below the mean for height. The peak growth hormone (GH) response to an insulin tolerance test (ITT) was 3.6 milliUnits per litre. With GH therapy he achieved a height (167cm) within the target height range. When reassessed at the age of 40, he remains GH deficient with a peak GH level of 6 milliUnits per litre to an ITT. The remainder of pituitary function has been normal through out his life. MR scan showed an atrophic anterior pituitary gland. His daughter is 10 years old; she is prepubertal and growing normally. Father's DNA has been analysed (personal communication D Bonneow) and a mutation in FOXL2 found. Abnormalities in the transcription factor FOXL2 represent a new cause of isolated GH deficiency.
08 - 11 Apr 2002
British Endocrine Societies