De-novo Williams-Beuren and inherited Marfan syndromes in a patient with developmental delay and lens dislocation

Abstract

This nonconsanguineous family included four family members affected by lens dislocation in three generations (Fig. 1a). The proband, a 6-year-old boy (Fig. 1b), was referred for evaluation of developmental delay. Following an uneventful pregnancy, he was delivered at 39 weeks' gestation by Caesarean section. Birth weight was 2000 g, length was 51 cm and Apgar score was 7. Developmental milestones were delayed: he walked alone at 24 months, babbled at 13 months and said his first words at 3 years. He had feeding difficulties with failure to thrive during his first year of life and was noted to have hypospadias, bilateral lens dislocation and frequent respiratory infections. At 6 years, his height was 110 cm (50th centile), weight was 19 kg (50th centile) and occipitofrontal circumference was 48 cm (<3rd centile), arm span was 130 cm and the arm span/height ratio was 1.18. He was noted to have facial dysmorphism (bitemporal narrowing, periorbital fullness, a broad nasal tip, long philtrum, a wide mouth with full lips, high-arched palate, small, widely spaced teeth and micrognathia), long fingers and toes and clinodactyly of the fifth fingers (Fig. 1b). He also had joint laxity, impaired fine motor activities and severe speech delay. Psychological evaluation showed severe mental retardation (IQ 30). He had a happy and sociable personality, hyperactivity, attention deficit, increased sensitivity to sounds, continuing feeding problems and a sleep disorder. Family history indicated that his mother, maternal uncle and maternal grandfather had been diagnosed with bilateral lens dislocation as teenagers. All these relatives had hyperlaxity, high-arched palates, long fingers, pectus carinatum and the wrist and thumb signs. The mother, 31 years old, had 170 cm height, 62 kg weight and 174 cm arm span; the uncle, 28 years old, had 187 cm height, 80 kg weight and 200 cm arm span (arm span/height ratio: 1.07); the maternal grandfather, 61 years old, had 180 cm height, 88.5 kg weight and 200 cm arm span (arm span/height ratio: 1.11).