ESPE Abstracts

Background: Patients with Klinefelter syndrome (SK) have a 47, XXY karyotype and tall stature as a result of overexpression of the SHOX gene. The case of a patient with peculiar phenotype, microcephaly, proportional short stature and 47, XXY karyotype with a deletion in band p11.3 of one X chromosome is presented.

Clinical description: A 2-year, 4 month-old boy was referred for study of growth retardation. The product of a first gestation of 39 weeks of healthy non-consanguineous parents of normal stature. BW: 2.850 g (−1.3 SD), length: 47.5 cm (−1.7 SD), PC: 33 cm (−1.0 SD). Physical exam: weight: 8.6 kg (−3.0 SD), length: 78 cm (−3.6 SD), CP: 40 cm (−2.0 SD). Phenotype: peculiar facies with narrow forehead and hypoplasia of nostrils. Microcephaly. Hypoplastic external genitalia. Testes in 1-cc sacs. Mild psychomotor retardation and axial hypotonia. Bone age: 2 years. Normal biochemical profile with normal coeliac disease markers. Hormone study: thyroid hormones: normal, LH <0.07 U/L, FSH 0.61 U/L, inhibin-B 113.0 pg/ml, ACTH 25.9 pg/ml, cortisol 18.6 mcg/dl, prolactin 6.1 ng/ml, IGF-1: 51.4 ng/ml, IGFBP-3: 3.6 ng/ml. Glucagon test: basal GH 4.4 ng/dl and maximum peak: 7.6 ng/dl. MR: pituitary hypoplasia, ectasia of the optic nerve sheath, ponto-cerebellar hypoplasia, mild demyelination of white matter. Array-CGH (ISCA v2, 8x60K, Agilent): presence of two X chromosomes and a deletion in Xp11.3 involving the CASK, NDP, KDM6A, GPR34, GPR82, MAOA, MAOB, EFHC2, FUNDC1 and DUSP21 genes (Default 1). 47, XXY Karyotype. FISH study with BAC RP11-24p8 confirmed the Xp11.3 deletion in the patient and was normal for the parents. Fundus: retinitis pigmentosa.

Conclusion: Array-CGH techniques are useful to orient the diagnosis of patients with severe growth retardation and dysmorphic phenotype. The combined effect of haploinsufficiency of the CASK gene and pituitary hypoplasia may be responsible for the short stature in our patient.