ESPE Abstracts

Background: Terminal or interstitial deletions of Xp (Xp22.2→Xpter) in males have been recognized as a cause of contiguous gene syndromes showing variable association of apparently unrelated clinical manifestations such as Leri-Weill dyschondrosteosis (SHOX), chondrodysplasia punctata (ARSE), mental retardation (NLGN4), ichthyosis (STS), Kallmann syndrome (KAL1), and ocular albinism (GPR143).

Case reports: We report two cases of boys with the same clinical features including hycthyosis, hypoacusis, short stature with short long bones, mental retardation, hypotelorism, strabismus, choanal stenosis and bilateral cryptorchidism. Case 1 was a boy born at 38 weeks of gestational age with a normal birth weight and birth length. At the age of 6 years and 10 months he was 99.5 cm (-4.1 SDS) compared to mid- parental-height of 169.5 cm (-1 SDS). ArrayCGH showed a terminal deletion in Xp22.31-33 region, maternally inherited, extended 6,1 Mb, including genes KAL1, STS, ARSE, NLGN4, SHOX. We started rhGH therapy at a dose of 0.035 mg/kg/day, increasing growth velocity from to 3.5 to 8 cm/year in the following three years, with a height gain of +1.3 SDS. At the age of 13 years he presented a decrease in growth velocity of 2 cm/yrs with a testicular volume of 2 ml bilaterally. GnRH-stimulation test showed a hypogonadotropic hypogonadism, so testosterone therapy was started. Case 2 was a boy born at 33 weeks of gestational age with a normal birth weight and length. At the age of 5 years and 7 months his height was 97 cm (-3.23 SD) with a mid-parental-height of 169 cm (- 1.1 SDS) and growth velocity of 4 cm/year. Array CGH showed a deletion in the region Xp22.31-33, maternally inherited, extended about 9.7 Mb. He started rGH therapy at a dose of 0.029 mg/kg/day with a height gain of +1 SDS in 2 years.

Conclusions: The two children presented a large terminal Xp22.31-33 deletion. Case 1 is the first Italian case of this contiguous gene syndrome, Case 2 had the longest terminal deletion reported in literature. We suggest, in order to improve the severe short stature in these patients, to start early the rhGH therapy for SHOX gene deletion and to optimize the induction of puberty according to the deletion of KAL1 gene, although short stature is also related to chondrodysplasia punctate.