Metacarpophalangeal pattern profile analysis in hypochondroplasia, dyschondrosteosis and Turner syndrome

Sammanfattning: The skeletal system, including the hand skeleton, is affected by a large number of skeletal dysplasias. Clinical and radiological abnormalities of the skeletal system in hypochondroplasia (HCP), dyschondrosteosis (LWD) and Turner syndrome (TS) may be rather subtle and difficult to recognize, particularly in young individuals, which can lead to an unnecessary delay of the diagnosis. Metacarpophalangeal pattern profile analysis (MCPP) proved to be useful in these cases. Tubular bones of the hand are measured on hand radiographs, normalized, and expressed in standard deviation scores (Z scores). Results, when presented graphically, reveal even minimal alterations of the bone lengths. In our first study we collected Swedish metacarpophalangeal length standards to be used for MCPP analysis in Swedish patients. Two sets of normative data, including total and diaphyseal bone lengths, have been presented. We compared Swedish standards with previously published norms and demonstrated that metacarpal and phalangeal bone lengths are population-specific and the choice of the standards, used in MCPP analysis, may significantly affect the final results. We therefore recommend using local standards whenever available in order to achieve the best results of MCPP analysis. In the next study we showed that hypochondroplasia has a distinct pattern profile which can be detected with MCPP analysis at any age. Discriminant analysis is capable of differentiating HCP from normal controls in 86%, from LWD in 85% and from TS in 90% of cases. We suggest that MCPP analysis should always be considered in patients with suspected HCP. In paper three we described MCPP in dyschondrosteosis. We demonstrated that it is distinct and significantly different from MCPP of normal controls. We showed that MCPP is not age-dependent feature and the specific pattern could be detected at any age, thus facilitating early diagnosis of LWD in patients with short stature. In our final study we showed that Turner syndrome has a characteristic pattern profile that can be detected by applying MCPP analysis at any age, regardless of the karyotype and severity of the phenotype. We suggest that MCPP analysis be applied in the girls with unexplained short stature whenever TS is suspected. We showed that hypochondroplasia, dyschondrosteosis and Turner syndrome have distinct pattern profiles significantly differing from that of normal controls and from each other. To our knowledge MCPP in dyschondrosteosis has not previously been described. Our studies showed MCPP to be an extremely constant feature that is not affected by increasing age or growth-promoting therapy. The shape of the profiles was not significantly correlated with the severity or presence of clinical or radiological abnormalities. MCPP demonstrated high sensitivity and specificity by discriminant analysis. Our results and previously published findings imply that hand pattern profile is determined early in fetal development and can be detected at birth by applying MCPP analysis. It can be used as a first choice method in girls with unexplained short stature for early diagnosis of hypochondroplasia, dyschondrosteosis and Turner syndrome. MCPP proved to be useful in distinguishing HCP, LWD and TS from each other. Computerized MCPP analysis increases the accuracy and reduces time consumption, thus making this method more effective, attractive and available for daily practice.