Clinical variability of Stickler syndrome with a COL2A1 haploinsufficiency mutation: implications for genetic counselling

Clinical variability in Stickler syndrome is well known,6 14 15 but correlations with specific mutations are scarce. We report a novel COL2A1 gene mutation found in a patient with flat face, cleft palate, myopia, and hearing loss (Stickler syndrome) and unexpectedly also in her father and her paternal grandmother who were considered to be healthy. The patient is the first child of healthy, non-consanguineous Swiss parents. The pregnancy was uneventful and she was delivered at term by caesarean section because of breech position. Birth weight was 3890 g (90th centile), birth length 50 cm (50th centile), and head circumference 37 cm (>97th centile). Macrocephaly and facial dysmorphism were noted in the neonatal period, including a flat midface, deep set ears, exophthalmos, palpebral oedema with telangiectasia, micrognathia, and median clefting of the soft and part of the hard palate (fig 1). No other abnormalities were recognised at that time. At the age of 5 years, midface hypoplasia and micrognathia were still evident. In addition, she presented with mild bilateral hypoacusis, bilateral myopia (4 dioptres), slight webbing of the neck, minimal pectus carinatum, and flat feet (fig 1). Her growth was on the 90th centile. The clinical signs and symptoms as well as radiological findings of mild spondyloepiphyseal dysplasia suggested the diagnosis of Stickler syndrome.