Abstract for presentation at 11th International Congress of Human Genetics

In 1994 Giuffrè et al. described a family with microcephaly (MC) and radio-ulnar synostosis (RUS) as main features. The pedigree of the family was most consistent with autosomal or X-linked dominant transmission of this new syndrome. They also reported another family: a boy showed intra-uterine growth retardation (IUGR), developmental delay, MC, RUS and some dysmorphologic signs. His sister had MC and RUS and his mother showed enlargement of the ulnar side of the radial head in X-rays, but no other features. Three more cases were reported, and the authors discussed whether these patients represent one condition with variable expression of the gene or genetic heterogeneity. We here report a 7-year-old boy presenting with IUGR, psychomotor delay, speech delay, attention deficit and hyperactivity disorder (ADHD), MC, bilateral RUS, 2/3 partial syndactyly of fingers, clinodactyly and brachymesophalangy of the fifth fingers, hypoplastic distal phalanges of all fingers, prominent and dysplastic ears, prominent nose, macrostomia, hydrocele, inguinal hernia on the right side and decreased mobility in ankle joints. Chromosome investigation and array CGH revealed normal results. The mother of the patient showed bilateral radio-ulnar deformity without psychomotor delay and MC; X-inactivation pattern studies revealed a non-random distribution. In summary we observed another case of RUS associated with MC, psychomotor retardation and other minor features in a male patient whose mother shows only mild radio-ulnar anomalies. The difference in expression between males and females affected with this pattern of anomalies points towards X-linked semi-dominant inheritance with much milder, but very variable manifestation in females due to variably skewed X-inactivation. We regard Giuffrè-Tsukahara syndrome as probably one condition with X-linked semi-dominant transmission and variable expression.