ESPE Abstracts

Background: Turner syndrome (TS) is classically a sporadic cause of short stature and gonadal dysgenesis in girls. We report familial variant TS affecting twelve individuals of both sexes over three generations. Affected children manifest short stature and varying degrees of neurodevelopmental disorder but no visceral abnormalities.

Case presentation: A 27-year-old female in her 12^th pregnancy presented for 20-week ultrasound. Fetal cardiac and renal anomalies led to amniocentesis, revealing terminal deletion of the short arm of one X chromosome at band 22.3, consistent with variant TS. This baby girl had pedal and hand oedema at birth. Echocardiogram was normal but kidneys remained echogenic. Speech and language delay became evident by preschool. Now 3-years-old, her height is on the 25^th centile. Seven other females (proband’s mother, half-sister, two half-aunts, three cousins and grandmother) and three males (proband’s half-brother and two cousins) carry the Xp22.3 deletion. They are short (height <2^nd centile). Five out of eight affected females also displayed disordered neurodevelopment. Two girls have speech and language delay. Three adult women have learning disability. All three affected boys manifest a more severe phenotype. Two have global developmental delay and autism. The third, now 12-weeks-old, was born premature, needed ventilatory support and is being investigated for Hirschsprung disease.

Conclusion: This is variant TS affecting both sexes in three generations of a family due to Xp22.3 deletion. Of the 42 known contiguous genes in Xp22.3, deletion of NLGN4, ARSE and SHOX may explain the phenotypes in this family (Online Mendelian Inheritance in Man, OMIM). NLGN4 deletion is linked to developmental delay and autism. ARSE deletion is associated with x-linked chondrodysplasia punctate (short stature with short distal phalanges). SHOX haploinsufficiency is considered solely responsible for short stature in TS. Familial variant TS should be considered in short boys with the relevant family history.