A TALL BOY

The most likely diagnosis is the connective tissue disease Marfan syndrome. This is an inherited synthetic disorder of fibrillin-1, a glycoprotein constituent of the microfibrils of elastic fibres that anchor non-elastic tissue such as the aortic adventitia and the suspensory ligament of the eye. By definition, tall stature includes all children with a length or height above the 98th centile. However, uncovering pathology in such children is rare and the vast majority have simple familial tall stature. This is characterized by a normal physical examination and serial height measurements that show no growth acceleration. Skeletal age (assessed by a bone age X-ray of the wrist) is usually slightly advanced in relation to chronological age, the child enters puberty relatively (not abnormally) early and completes their growth phase relatively early, with a final height within the expected range for their family. The differential diagnosis of familial tall stature is a syndrome associated with tall stature, such as Marfan or Klinefelter (47, XXY) syndrome, or a child with growth acceleration for which an endocrine cause is likely, e.g. sexual precocity, thyrotoxicosis or growth hormone excess. Children with familial tall stature rarely benefit from further investigations or monitoring. The diagnosis of Marfan syndrome is made on accepted clinical criteria – only about 60–70 per cent of patients who fulfil these have an identifiable mutation in the fibrillin gene. This boy displays many of the musculoskeletal features – arm span to height ratio 1.05, arachnodactyly with a positive thumb sign and pectus excavatum – but many other systems may be involved. Most important are the eyes and heart. Lens dislocation is one of the major criteria for diagnosis and he needs a slit-lamp examination. His murmur is typical of mitral valve prolapse (MVP) and echocardiography is essential for diagnosis and to monitor the high risk of progressive aortic root dilatation. Marfan syndrome is an autosomal dominant disorder, although about 30 per cent arise sporadically. There is the distinct possibility that this boy has inherited it from his father, who is unusually tall for his family and should be investigated. There is significant morbidity and reduced longevity, mainly from the cardiovascular complications, but young adults like him may still be asymptomatic. However, making such a diagnosis will have far-reaching social, financial and psychological consequences for an individual and their family. Referral to the genetics team is mandatory: first, to obtain informed consent for investigations; second, to confirm the diagnosis; and third, to counsel about recurrence and inheritance risk – in Marfan this is 50 per cent. Refuting a diagnosis is obviously just as important in uncertain cases and the geneticists are best placed to do so.

KEY POINTS

• Pathological causes of tall stature are rare.

• Families who may have serious inheritable disorders must be referred to genetics teams for diagnosis and counselling.