Body Segment Ratio Research Articles

Assessment of upper to lower body segment ratio and arm span to height difference in school children of Lahore.

To assess upper-to-lower body segment ratio and arm span to height difference in children. The descriptive, cross-sectional study was conducted in schools of the Raiwind area near Lahore, Pakistan, from November 2021 to May 2022, after approval from the ethics review committee of the Sharif Medical and Dental College, Lahore. The sample comprised children aged 3-14 years whose height fell between the 3rd and 97th centiles on the Centers for Disease Control and Prevention height-for-age chart. Data was analysed using SPSS 23. Of the 1,836 children, 906(49.3%) were boys with mean age 8.45±3.02 years, mean height 132.54±17.78cm and mean weight 32.0±13.72kg. Besides, there were 930(50.7%) girls with mean age 8.26±3.21 years, mean height 130.41±18.03cm and mean weight 31.09±13.88kg. The mean upper-to-lower body segment ratio in boys was 1.06±0.15 at age 3 years, 0.96±0.08 at age 7 and 0.94±0.08 at age 10. The mean upper-to-lower body segment ratio in girls was 1.08±0.08 at age 3 years, 0.98±0.07 at age 7, and 0.92±0.10 at age 10. The mean arm span to height difference in boys was -1.81±5.83 and in girls -4.09±5.77. Upper-to-lower body segment ratio and arm span to height difference may help paediatricians in the evaluation of disproportionate short stature.

LBMON196 A Randomized Controlled Trial Of Vosoritide In Infants And Toddlers With Achondroplasia

Abstract Background Vosoritide increases annualized growth velocity (AGV) in children with achondroplasia aged 5 to 18 years. This global, phase 2, randomized, double-blind, placebo-controlled study evaluated the safety and efficacy of vosoritide on growth in children with achondroplasia aged 3 months to <5 years. Methods This study compared once-daily subcutaneous administration of vosoritide, at doses of 15 or 30 μg/kg of body weight, with placebo. Eligible patients had participated, for up to 6 months, in an observational growth study to calculate their baseline AGV. The primary objective was to evaluate the safety and tolerability of vosoritide in children with achondroplasia. The primary efficacy evaluation was the change from baseline in height Z-score versus placebo at week 52 using an ANCOVA model. Secondary efficacy analyses included change from baseline in AGV and upper-to-lower body segment ratio versus placebo at Week 52 using an ANCOVA model. Results A total of 75 patients were enrolled, with 11 sentinel subjects who received vosoritide to establish PK and safety. A further 32 were randomized to receive vosoritide and 32 to receive placebo. A total of 73 patients completed the 52-week trial. All patients reported at least one adverse event. Four serious adverse events occurred with vosoritide and 8 with placebo, none were treatment-related. Two participants discontinued, one on vosoritide with pre-existing respiratory morbidity who had a fatal respiratory arrest and one on placebo who withdrew consent. In the full analysis population, vosoritide (n=43) compared to placebo (n=32), increased height Z-score by 0.30 SD (95% CI 0. 07, 0.54); increased AGV by 0.92cm/year (95% CI 0.24, 1.59); and did not worsen upper-to-lower body segment ratio which changed by -0. 06 (95% CI -0.15, 0. 03). Conclusions Daily, subcutaneous administration of vosoritide to young children with achondroplasia was safe and resulted in increases in height Z-score and AGV. (Funded by BioMarin; ClinicalTrials.gov NCT03583697) Presentation: Monday, June 13, 2022 12:30 p.m. - 2:30 p.m.

Vosoritide in achondroplasia: a profile of its use

Subcutaneous vosoritide (Voxzogo®), a modified recombinant human C-type natriuretic peptide (CNP) analogue, is the first precision therapy approved for the treatment of achondroplasia in the EU, USA and multiple other countries. It is indicated for patients aged ≥ 2 years with open epiphyses in the EU and those aged ≥ 5 years with open epiphyses in the USA. In a phase 3 trial (study 111-301), vosoritide 15 μg/kg/day significantly improved annualized growth velocity and height Z-score compared with placebo, without worsening upper-to-lower body segment ratio in children with achondroplasia. The growth-promoting effects of vosoritide persisted with continued treatment for up to 60 months. Vosoritide is generally well tolerated, with most adverse events being mild in severity. Longer-term safety data revealed no new safety signals. Achondroplasia is the most common form of skeletal dysplasia and is characterized by short stature with disproportionate bone growth. The condition is caused by a gain-of-function mutation in the gene for fibroblast growth factor receptor 3 (FGFR3), which is a negative regulator of bone growth. With increased understanding of the pathogenesis of achondroplasia, vosoritide (Voxzogo®), a modified recombinant human C-type natriuretic peptide (CNP) analogue, has been approved as the first precision therapy for the treatment of achondroplasia in patients aged ≥ 2 years with open epiphyses in the EU and those aged ≥ 5 years with open epiphyses in the USA. In children with achondroplasia, daily subcutaneous administration of vosoritide was associated with growth-promoting effects. Vosoritide is generally well tolerated, with most adverse events being mild in severity. Thus, vosoritide is a valuable, effective and generally well-tolerated treatment option for children with achondroplasia.

Growth parameters in children with achondroplasia: A 7-year, prospective, multinational, observational study

This study was undertaken to collect baseline growth parameters in children with achondroplasia who might enroll in interventional trials of vosoritide, and to establish a historical control. In this prospective, observational study, participants (≤17 years) underwent a detailed medical history and physical examination and were followed every 3 months until they finished participating in the study by enrolling in an interventional trial or withdrawing. A total of 363 children were enrolled (28 centers, 8 countries). Mean (SD) follow up was 20.4 (15.0) months. In participants <1 year, mean annualized growth velocity (AGV) was 11.6 cm/year for girls and 14.6 cm/year for boys. By age 1 year, mean AGV decreased to 7.4 cm/year in girls and 7.1 cm/year in boys. By age 10 years, mean AGV decreased to 3.6 cm/year for both sexes. Mean height z-score in participants <1 year was -2.5 for girls and-3.2 for boys and decreased up to the age 5 years (-5.3 for girls;-4.6 for boys). Girls and boys had a disproportionate upper-to-lower body segment ratio. Mean ratio was highest in participants aged <1 year (2.9 for girls; 2.8 for boys) and decreased gradually to approximately 2 in both sexes from 4 years of age onward. This study represents one of the largest datasets of prospectively collected medical and longitudinal growth data in children with achondroplasia. It serves as a robust historical control to measure therapeutic interventions against and to further delineate the natural history of this condition.

Literature review and expert opinion on the impact of achondroplasia on medical complications and health-related quality of life and expectations for long-term impact of vosoritide: a modified Delphi study

BackgroundAchondroplasia is associated with disproportionate short stature and significant and potentially severe medical complications. Vosoritide is the first medicine to treat the underlying cause of achondroplasia and data from phase 3 and phase 2 extension studies showed effects on growth and body proportions. However, there are currently no long-term data available on the direct impact on endpoints such as medical complications and health-related quality of life (HRQoL). This study explored the perceived impact of achondroplasia on medical complications, HRQoL, healthcare resource use and mortality, and potential modifying effects of vosoritide, based on published evidence and expert opinion. Structured expert opinion was obtained by an international modified Delphi study among 14 experts in managing achondroplasia performed on a virtual platform and consisting of an explorative phase followed by an anonymous individual rating round.ResultsOverall, the panelists expect that in individuals starting long-term treatment between 2 years of age and puberty, growth velocity increases observed in the clinical trials will be maintained until final height is reached (92% agreement) and will likely result in clinically meaningful improvements in upper-to-lower body segment ratio (85%). Earlier treatment initiation will likely result in a greater final height (100%) and more likely improve proportionality (92%) than later treatment. Although current data are limited, ≥ 75% of panelists find it conceivable that the earlier long-term treatment is started, the greater the probability of a positive effect on the lifetime incidence of symptomatic spinal stenosis, kyphosis, obstructive sleep apnea, and foramen magnum stenosis. These are among the most clinically important complications of achondroplasia because of their high impact on comorbidity, mortality, and/or HRQoL. A positive effect of vosoritide on the incidence of surgeries through lifetime was considered more likely with earlier long-term treatment (90%).ConclusionsThis explorative study, based on international expert opinion, provides further insight into the medical and functional impacts of achondroplasia and how these might be modified through long-term use of vosoritide. The results can be used to guide the direction and design of future research to validate the assumptions and to discuss potential treatment outcomes with disease modifying therapies with families and clinicians.

Persistent and Stable Growth Promoting Effects of Vosoritide in Children With Achondroplasia for up to 2 Years: Results From the Ongoing Phase 3 Extension Study

Objectives: Vosoritide is a potent stimulator of endochondral bone growth and is in development for the treatment of achondroplasia, the most common form of disproportionate short stature. We previously reported on a 52-week, phase 3, pivotal study that demonstrated a highly statistically significant improvement in annualized growth velocity (AGV) when vosoritide was compared to placebo in children with achondroplasia aged 5-18 years (Savarirayan et al, Lancet, 2020). This is an analysis of data after an additional 52 weeks of treatment in the ongoing phase 3 extension study. Methods: After completion of the phase 3 placebo-controlled study, 119 children were enrolled into the extension study, where they all receive open label 15 μg/kg/day vosoritide. AGV, height Z-score and body proportion ratio were analyzed to assess efficacy of vosoritide in children who were treated with vosoritide for up to 2 years. Fifty-eight continued treatment with vosoritide and 61 switched from placebo to vosoritide. Two participants on continuous vosoritide treatment discontinued before the Week 52 timepoint. Four participants on continuous vosoritide treatment and 7 participants who switched from placebo to vosoritide missed the Week 52 assessment due to Covid-19. Results: In children randomized to receive daily vosoritide, baseline mean (SD) AGV was 4.26 (1.53) cm/year. After the first 52 weeks of treatment, mean (SD) AGV was 5.67 (0.98) cm/year. Mean (SD) AGV over the second year was 5.57 (1.10) cm/year. Mean (SD) change from baseline in height Z-score improved by +0.24 (0.31) at Week 52 in the pivotal study and +0.45 (0.56) at Week 52 in the extension study. Mean (SD) upper-to-lower body segment ratio improved with a change from baseline of -0.03 (0.11) at Week 52 in the pivotal study and -0.09 (0.11) at Week 52 in the extension study. In children who switched from placebo to vosoritide after 52 weeks, baseline AGV was 4.06 (1.20) cm/year and 3.94 (1.07) cm/year after 52 weeks on placebo. In the second year, after receiving 52 weeks of vosoritide, mean AGV was 5.65 (1.47) cm/year, the mean (SD) change in height Z-score was +0.24 (0.34), and the change in upper-to-lower body segment ratio was -0.03 (0.08). No new adverse events associated with vosoritide treatment were detected with up to 2 years of continuous daily, subcutaneous treatment. Most adverse events were mild and no serious adverse events were attributed to vosoritide. The most common adverse event remains mild and transient injection site reactions. Conclusions: The effect of vosoritide administration on growth as measured through AGV and height Z-score was maintained for up to 2-years in children with achondroplasia aged 5 to 18 years, with an improvement of body proportions.

Design of the ACcomplisH Trial: A Phase 2, Multicenter, Placebo-Controlled, Dose Escalation Trial Evaluating Safety, Efficacy, and Pharmacokinetics of Weekly TransCon CNP in Children With Achondroplasia

Abstract Background: Achondroplasia (ACH) is the most common skeletal dysplasia and the most frequent form of dwarfism. ACH is caused by a gain-of-function mutation in the fibroblast growth factor receptor 3 (FGFR3) gene and results in impairment of the endochondral ossification processes. C-type natriuretic peptide (CNP) promotes chondrocyte development through inhibition of the FGFR3 pathway, specifically through activation of NPRB. CNP is a desirable target as it is known to increase chondrocyte development without off-target effects (Bocciardi, 2007). TransCon CNP is a long-acting prodrug of CNP designed to optimize safety and efficacy with a once-weekly dose. The Phase 1 clinical trial with TransCon CNP demonstrated that doses up to 150 μg CNP/kg were well-tolerated in healthy adult male volunteers, with no clinically significant trends observed in clinical laboratory assessments, vital sign measurements, ECG parameters, or physical examination findings. Methods: The phase 2 ACcomplisH trial will be conducted at over 35 sites worldwide. The primary objective of the trial will be to evaluate the safety and efficacy of once-weekly TransCon CNP compared to placebo at 12 months in prepubertal children, aged 2-10 years old, with ACH. Approximately 60 subjects will be randomized 3:1 to receive either weekly TransCon CNP or placebo. Following screening and verification of clinical ACH with genetic confirmation, subjects will remain within the dose cohort for 52 weeks of treatment. TransCon CNP will be dosed 6 to 100 μg CNP/kg/week across 4 cohorts, with an optional 5th cohort at up to 200 μg CNP/kg/week. An independent Data Monitoring Committee will review safety data prior to initiation of a higher dose cohort. The primary endpoint will evaluate annualized height velocity at 52 weeks of TransCon CNP or placebo. Key secondary endpoints will examine change in upper to lower body segment ratio at week 52, safety, pharmacokinetics (PK), and quality of life associated with weekly TransCon CNP. Conclusion: CNP is targeted specifically to the underlying pathology of ACH through inhibition FGFR3. No effective medicinal product is currently available for the treatment of ACH. TransCon CNP is designed to provide sustained exposure of CNP. This ongoing Phase 2 ACcomplisH trial is designed to assess the efficacy, safety, and PK of TransCon CNP by weekly administration compared to placebo.

Upper body segment to lower body segment and arm span to height ratios among children with sickle cell anaemia in Lagos

Objective : To determine ratios of upper body segment to lower body segment and arm span to height in the sickle cell anaemia patients Background : Sickle cell anaemia may adversely affect linear growth and body proportions. Methods : Height, upper segment and arm span were measured in 100 sickle cell anaemia patients aged eight months to 15 years and 100 age/sex matched controls. Lower body segment length, upper body segment to lower body segment ratio, and arm-span to height ratio were derived. Results : Sickle cell anaemia subjects older than 10 years had significantly shorter upper body segment than controls (p = 0.035 and p = 0.004 for males and females respectively). The mean upper segment/lower segment ratio decreased with age among primary subjects (SS) and AA controls. In comparison with AA controls, female sickle cell anaemia subjects older than 10years had significantly lower mean upper body segment to lower body segment ratio (p = 0.005). Mean arm span was significantly shorter in male sickle cell anaemia patients older than 5 years (p = 0.034 at 5 to 10 years and p = 0.029 at . 10 years) and in females older than 10 years than in controls (p = 0.025). The mean arm span/height ratio was lower in sickle cell anaemia subjects than controls, except in males younger than five years. Conclusions : Sickle cell anaemia patients older than 10 years have shorter mean upper segment. In this age group, females also had significantly lower upper segment to lower segment ratio. Keywords : sickle cell anaemia, upper body segment, lower body segment, ratio

A Rare Presentation of the Klinefelter's Syndrome.

A 16 years old boy with Chronic Renal Failure (CRF) was not suspected of having Klinefelter's syndrome until he complained of painful gynecomastia. He was under haemodialysis for 2 years. At first, he was in an approximately full pubertal development (P5, G5), but he had a small and a firm testis (length 2.2cm) and some degree of facial male pattern hair. He also had a decreased upper to lower body segment ratio and despite having chronic renal failure, he was taller than his parents and siblings. His laboratory tests showed high levels of FSH and normal levels of LH and testosterone. With regards to all these findings, we suspected that there might be an occult Klinefelter's syndrome. So, we made his karyotype that showed a 47XXY pattern. Because there are only a few number of cases that have occult Klinefelter's syndrome in the basis of chronic renal failure, we decided to report this case.

Anthropometric, penile and testis measures in post-pubertal Italian males.

Relationships between anthropometric measures, body proportions, weight and penile dimensions in young adult males have not been previously analyzed. Furthermore, although male fertility has declined in last decades, no data on testicular volume (the best surrogate measure for spermatogenic potential) are available for the general population of young men in Italy. To analyze anthropometric measures and proportions, testicular volumes, and penile dimensions in a large cohort from the general population of young Italian men aged 18-19 yr. MATERIALS/SUBJECTS: We analyzed 2019 students aged 18-19 years for height, weight, body mass index (BMI), waist circumference, arm span, pubis-to-floor and crown-to-pubis length, and penile dimensions. Testicular volumes were measured by ultrasound in 776 subjects. Thirty-six percent of the subjects had a pathological arm span-height difference (>3 cm) and 44.7% had a pathological pubis-to-floor/ crown-to-pubis ratio (≤ 0.92). The mean penis length was 8.9 ± 1.4 cm and the penis circumference was 9.5 ± 1.0 cm. BMI was positively associated with arm span-height difference and negatively with penis length; 23.2% of the subjects had low mean testicular volume (<12 ml). The findings highlight a strong influence of BMI on skeletal proportions and penis length, identify a large proportion of subjects with testicular hypotrophy at risk for future fertility, and suggest to consider worldwide studies to redefine normal values for arm span-height difference and upper/ lower body segment ratio.

Differential effects of hGH and IGF-I on body proportions

The differential growth effects of hGH and IGF-I on the upper/lower (U/L) body segment in relation to height (Ht) were analyzed in 15 patients with isolated Growth hormone deficiency (IGHD,:7M, 8F) mean age 5.0 +/- 3.2 (SD) years treated with hGH; 21 patients with multiple pituitary hormone deficiency including growth hormone (MPHD: 14M, 7F) aged 10.0 +/- 3.8, treated with hGH; 9 patients with Laron Syndrome (LS) (4M,5F) aged 6.9 +/- 5.6 years treated with IGF-I; 9 boys with intrauterine growth retardation (IUGR) aged 6.3 +/- 1.25 years treated by hGH; and 22 boys with idiopathic short stature (ISS) aged 8.0 +/- 1.55 years treated by hGH. The dose of hGH was 33 microg/kg/day, that of IGF-I 180-200 microg/kg/day. the U/L body segment ratio in IGHD patients decreased from 2.3 +/- 0.7 to 1.1 +/- 0.7 (p <0.001), and the Ht SDS increased from -4.9 +/- 1.3 to 2.3 +/- 1 (p < 0.001) following treatment. In MPHD patients the U/L body segment decreased from 1.1 +/- 1.1 to -0.6 +/- 1.0 (p < 0.001), and the Ht SDS increased from -3.3 +/- 1.4 to -2.5 +/- 1.0 (p < 0.009). In the LS group the U/L body segment ratio did not change with IGF-I treatment but Ht improved from -6.1 +/- 1.3 to -4.6 +/- 1.2 (p < 0.001), The differential growth response of the children with IUGR and with ISS resembled that of the children with LS. hGH and IGF-I act differentially on the spine and limbs.

Anthropometric and Skeletal Phenotype in Men with Idiopathic Osteoporosis and Their Sons Is Consistent with Deficient Estrogen Action during Maturation

Pathophysiology of deficient bone mass acquisition in male idiopathic osteoporosis (IO) remains poorly understood. Our objective was to investigate volumetric and geometric parameters of the appendicular skeleton, biochemical markers, and anthropometrics in men with IO. Our cross-sectional study included 107 men diagnosed with idiopathic low bone mass, 23 of their adult sons, and 130 age-matched controls. Body composition and areal bone parameters (dual-energy x-ray absorptiometry) and volumetric and geometric parameters of radius and tibia (peripheral quantitative computed tomography) were assessed. Serum levels of testosterone, estradiol (E(2)), and SHBG, and bone turnover markers were measured using immunoassays. Free hormone fractions were calculated. Men with idiopathic low bone mass had lower weight (-9.6%), truncal height (-3.3%), and upper/lower body segment ratio (-2.7%; all P < 0.001) and presented at the radius and tibia lower trabecular (-19.0 and -23.6%, respectively; both P < 0.001) and cortical volumetric bone mineral density (vBMD) (-2.4 and -1.7%; both P < 0.001) and smaller cortical areas (-9.7 and -13.6%; both P < 0.001) and thicknesses (-13.5 and -14.5%, both P < 0.001) due to larger endosteal circumferences (+11.8 and +7.4%, both P < 0.001) than controls. Furthermore, (free) E(2) was lower and SHBG higher (both P < 0.01). Their sons had lower trabecular vBMD (-10.3%, P = 0.036) and a thinner cortex (-8.3%, P = 0.024) at the radius. Bone mass deficits in men with idiopathic low bone mass involve trabecular and cortical bone, resulting from lower vBMD and smaller cortical bone cross-sectional areas and thicknesses. A similar bone phenotype is present in at least part of their sons. The lower E(2), together with characteristics as lower upper/lower body segment ratio, larger endosteal circumferences and lower vBMD, may indicate an estrogen-related factor in the pathogenesis of male IO.

Final height in a patient with Laron syndrome after long-term therapy with rhIGF-I and short-term therapy with LHRH-analogue and oxandrolone during puberty

To report our experience on long-term treatment with recombinant-human-IGF-I (rhIGF-I) of a female patient with Laron syndrome (mutation G223G in the GH receptor gene), who received short-term treatment (1 yr) with LHRH analogue at the start of puberty and subsequently with oxandrolone. The patient started IGF-I therapy (dose 40 microg/kg bid for 9 months, 80 microg/kg bid until 13.7 yr of age and 120 microg/kg bid thereafter) when she was 7.6 yr old (height -6 sds), and was treated for 9.4 yr until final height (cm 129.7; -5.5 sds). At first signs of puberty (age 12.7 yr; height 116.3; -5.3 sds), LHRH analogue was started (3.75 mg/28 days) and bone age progressed by 6 months in the 12-month period. Growth velocity decreased in the 6-12th month of combined treatment (0.9 cm/6 months), and treatment was suspended. At age 14.8 (height 124.5; -6.6 sds), oxandrolone was added (0.1 mg/kg/day), but after 12 months (height 128 cm; -5.7 sds) bone age increased from 11.5 to 13.5 yr and the drug was stopped. No side effects occurred during the various treatments. Body segments progressed harmonically: there was a tendency towards improvement in the upper to lower body segment ratio and in cranial growth. Only biiliac diameter did not increase during LHRH treatment. During the 9-yr period, body mass index (BMI), subscapular and triceps skinfold centiles did not show any significant variations. Our patient with Laron syndrome after long-term treatment showed a final result below the initial expectations, confirming that IGF-I used with the present schedule is less effective than GH in GH-deficient patients. LHRH analogue therapy at puberty was associated with a slower bone age maturation but with an almost complete arrest of growth. On the contrary, oxandrolone sustained growth but caused an excessive maturation of bone age. Other strategies are necessary to improve final height in these patients.

Two sibs with brachyolmia type Hobaek: five year follow-up through puberty.

A brother and a sister affected with brachyolmia (short trunk) are reported. Their radiological findings are compatible with brachyolmia, Hobaek type, which is characterized by platyspondyly, horizontal acetabular roof, short femoral neck, and vertical "mixed lucent and dense" striation pattern in the metaphyses of large long bones. Despite normal birth weight and length, the platyspondyly is present at infancy, but clinically the condition may not be noticeable until late childhood or early puberty, when stunted growth becomes apparent. Beyond puberty, the patients are short in stature, mainly due to a short trunk with decrease upper and lower body segment ratio. Brachyolmia type Hobaek is a relatively benign condition. It may cause a mild and nonspecific backache that usually is not debilitating. The inheritance mode is apparently autosomal recessive.

Growth curves for Laron syndrome.

Growth curves for children with Laron syndrome were constructed on the basis of repeated measurements made throughout infancy, childhood, and puberty in 24 (10 boys, 14 girls) of the 41 patients with this syndrome investigated in our clinic. Growth retardation was already noted at birth, the birth length ranging from 42 to 46 cm in the 12/20 available measurements. The postnatal growth curves deviated sharply from the normal from infancy on. Both sexes showed no clear pubertal spurt. Girls completed their growth between the age of 16-19 years to a final mean (SD) height of 119 (8.5) cm whereas the boys continued growing beyond the age of 20 years, achieving a final height of 124 (8.5) cm. At all ages the upper to lower body segment ratio was more than 2 SD above the normal mean. These growth curves constitute a model not only for primary, hereditary insulin-like growth factor-I (IGF-I) deficiency (Laron syndrome) but also for untreated secondary IGF-I deficiencies such as growth hormone gene deletion and idiopathic congenital isolated growth hormone deficiency. They should also be useful in the follow up of children with Laron syndrome treated with biosynthetic recombinant IGF-I.

Linear growth in a population of children with myelomeningocele.

Short stature or total body length less than the third percentile for age was present in 51% of our children with myelomeningocele. It was particularly common in children with higher spinal lesions where 77% of the children with L3 and higher lesions had length measurements less than the 3rd percentile for age. None of the children with sacral lesions was of short stature. Associated musculoskeletal deformities of the spine, hips, and knees made total body length and upper to lower body segment ratio measurements both difficult to obtain and less than ideal parameters for assessing linear growth. Arm span measurements, however, were easily obtained in or out of braces and were greater than expected for length in 91% of children with short stature older than 3 years of age. This apparent sparing of arm span in many of our children makes it a valuable growth parameter when assessing linear growth and in turn an important diagnostic tool for the monitoring of total health in a population of children with myelomeningocele.

The XXXY Klinefelter syndrome in childhood.

The XXXY variety of Klinefelter syndrome should be suspected when the following features are observed in a mentally retarded boy: decreased upper-lower body segment ratio, microcephaly, clinodactyly with brachymesophalangia of the fifth fingers, and dermatoglyphic arches on nine or ten fingers associated with attriradius in t 1 position. These features are not puberty-dependent like the endocrine characteristics of Klinefelter syndrome and, therefore, permit an early diagnosis.