Metacarpal index in Marfan's syndrome and in constitutional tall stature.

The metacarpal index (MCI) in 54 children with constitutional tall stature was mean (SD) 8.65 (0.8) and in 55 with Marfan's syndrome 9.15 (0.9). Indices in both groups showed arachnodactyly and differed from those found in normal individuals (< 7.9). Because the MCI is a poor discriminator patients with tall stature or clinical signs of arachnodactyly should be examined for additional signs of Marfan's syndrome or other hereditary disorders of connective tissue.     

Association of Marfan's syndrome and Turner's syndrome.

We report on a 12 year-old girl with severe myopia, ectopia lentis, dilatation of the ascending aorta, protrusio acetabulae, arachnodactyly, scoliosis and moderate short stature (-1.7 SD). Her sister and father presented with Marfan's syndrome. Despite short stature, Marfan's syndrome could not be ruled out. Primary amenorrhoea and growth retardation indicated cytogenetic analysis which showed chromosomal aberration 45,X in every studied cell. However, she did not present any other clinical features of Turner's syndrome. We report here for the first time on an association of Turner's syndrome and Marfan's syndrome in the same patient, and discuss particular clinical features.     

The Beals-Hecht syndrome (congenital contractural arachnodactyly) revealed in a neonate

A new case of congenital contracture arachnodactyly (CCA) revealed in the neonatal period is reported. CCA is a dominantly inherited syndrome associating arachnodactyly, kyphoscoliosis, multiple congenital joint contractures and crumpled ears. This condition differs from Marfan's syndrome by the usual absence of visceral involvement, although cardiac complications are possible. The neonatal forms result from new mutations are are generally severe.     

Do centimetres matter? Self‐reported versus estimated height measurements in parents

Aim: An impressive discrepancy between reported and measured parental height is often observed. The aims of this study were: (a) to assess whether there is a significant difference between the reported and measured parental height; (b) to focus on the reported and, thereafter, measured height of the partner; (c) to analyse its impact on the calculated target height range. Methods/Results: A total of 1542 individual parents were enrolled. The parents were subdivided into three groups: normal height (3–97th Centile), short (<3%) and tall (>97%) stature. Overall, compared with men, women were far better in estimating their own height (p < 0.001). Where both partners were of normal, short or tall stature, the estimated heights of their partner were quite accurate. Women of normal stature underestimated the short partner and overestimated the tall partner, whereas male partners of normal stature overestimated both their short as well as tall partners. Women of tall stature estimated the heights of their short partners correctly, whereas heights of normal statured men were underestimated. On the other hand, tall men overestimated the heights of their female partners who are of normal and short stature. Furthermore, women of short stature estimated the partners of normal stature adequately, and the heights of their tall partners were overestimated. Interestingly, the short men significantly underestimated the normal, but overestimated tall female partners. Conclusion: Only measured heights should be used to perform accurate evaluations of height, particularly when diagnostic tests or treatment interventions are contemplated. For clinical trails, we suggest that only quality measured parental heights are acceptable, as the errors incurred in estimates may enhance/conceal true treatment effects.     

Metacarpal index in short stature before and during growth hormone treatment

AIMS—To assess the usefulness of the metacarpal index (MCI) as a radiographic measure of the proportions of the metacarpals in the differential diagnosis of short stature. To investigate the significance of the MCI in following the longitudinal growth and proportions of individual long bones during growth hormone stimulated catch up growth in children with short stature with and without growth hormone deficiency.
SUBJECTS—124 children, including 65 children with short stature caused by growth hormone deficiency, 13 with familial short stature, 29 with idiopathic short stature, and 17 with Ullrich-Turner syndrome.
METHODS—Retrospective analysis of the MCI in five posterior-anterior radiographs of the left hand of all patients, which were performed sequentially for routine bone age determinations (Greulich and Pyle) before and during the first three years of growth hormone treatment.
RESULTS—The MCI was similar in all patient groups, resembled that of healthy children, and correlated significantly with chronological age, bone age, and height before and during growth hormone treatment. Despite a remarkable growth hormone stimulated catch up growth, the MCI did not change significantly during growth hormone treatment.
CONCLUSIONS—The role of the MCI is insignificant in the diagnosis of short stature, but the MCI can serve as an auxological measure of osseous proportions during longitudinal growth. Growth hormone treatment accelerates longitudinal growth without affecting the proportions of the long bones, indicating that growth hormone stimulated bone growth closely resembles spontaneous bone growth.

     

Radiographic findings in Shprintzen-Goldberg syndrome

We report the case of a Japanese boy whose dysmorphic features were consistent with those of Shprintzen-Goldberg syndrome. The radiological features were characterized by late-onset craniosynostosis, arachnodactyly, undermodeling of short tubular bones, mildly undermodeled and slightly bowed long bones, twisted ribs and tall vertebral bodies with elongated neural arches. Apart from the craniosynostosis, these skeletal changes resembled those of frontometaphyseal dysplasia, a well-known craniotubular dysplasia. Shprintzen-Goldberg syndrome also shares many clinical features with frontometaphyseal dysplasia.     

Fulminant acne in Klinefelter syndrome treated with testosterone. A side effect of anti-tallness therapy

Acne lesions usually do not occur in patients with Klinefelter's syndrome (47 XXXY). But a 19 year old patient with Klinefelter's syndrome, under therapy with testosteronenantat (500 mg every two weeks over a period of 18 months) for treatment of excessively tall stature developed acne fulminans. Following discontinuation of testosterone treatment and isotretinoin therapy over 16 weeks skin lesions healed almost completely although with severe scars. In conclusion, high doses testosterone-treatment in excessively tall boys needs the additional care of dermatologist when mostly after a 7 months period acne begins to develop under this treatment.     

Diagnostic approach and therapy of overgrowth and tall stature in childhood

Although referral for evaluation of tall stature is much less common than for short stature, early diagnosis in the paediatric age of clinical pictures leading to tall stature is crucial, both in order to detect conditions which can be properly treated and in order to limit excessive final heights; nowadays tall stature may be cause of psychosocial problems. This paper reviews different items related to tall stature in childhood. First of all, our review focuses on the definition of tall stature and the classification of the main clinical conditions associated with either tallness or excessive growth is discussed. Secondly, the clinical picture and the most recent breakthroughs of each of these conditions are reviewed. A diagnostic flow-chart meant to approach a patient presenting with tall stature is designed according to a few simple parameters such as chronological age, height age, bone age and growth velocity. The novel advances in the understanding of constitutional and secondary tall stature are presented and discussed, together with the hormonal treatment of constitutional tall stature and other related outstanding questions.     

Frequent growth disorders in puberty and adolescence

About 50% of our patients with concern about their actual or final height are adolescents (girls greater than 11 years, boys greater than 13 years). Growth data of 103 adolescent patients (70 boys, 33 girls) seen in 1988/89 are analysed. 85% of the patients (90% of the boys) complained of short stature (length less than 3rd centile) whereas tall stature (height greater than 97th centile) was more frequently concerning girls (9 out of 16 patients). Genetic short stature and constitutional delay of growth and adolescence (CDGA) were most often diagnosed in short stature patients. When retardation of physical maturation is a major concern in patients with CDGA, treatment with a low dose of sex steroids leads to an acceleration of growth and pubertal development. This advancement of maturation is important for reducing the psychosocial difficulties of the concerned adolescents. Constitutional tall stature was the most frequent diagnosis in our tall adolescent patients. If predicted final height is above 185 cm for girls or 200 cm for boys the administration of height dose sex steroids (ethinylo-estraidol or conjugated oestrogen for girls, testosteron for boys) for height reduction can be tried, since a reduction in height between 3.5 cm and 7.9 cm has been reported for girls and similar data exists for boys. Nevertheless a cautious approach must be advocated for the administration of oestrogens because possible long term hazards can not yet be excluded.     

Extreme Tall Stature in a Japanese Boy with a 48,XXYY Karyotype

We report an 18-yr-old Japanese boy with a 48,XXYY karyotype and extreme tall stature (194 cm). A GnRH test at 12.5 yr of age showed hypergonadotropism (LH, 4.2 → 72.2 mIU/mL; FSH, 28.9 → 61.7 mIU/mL), and an hCG test at 15.5 yr of age revealed a normal testosterone response (1.67 → 4.08 ng/mL). The tall stature is remarkable, because the mean adult height of Caucasian 48,XXYY patients is 181 cm. Although the underlying factors for the tall stature are unknown, this report indicates an association of the 48,XXYY karyotype with marked tall stature.     

Current concepts in tall stature and overgrowth syndromes

In this overview an update is given on the pathogenesis, classification and differential diagnosis of overgrowth syndromes. In addition, height prognosis and therapeutic modalities available for managing mainly constitutional tall stature are discussed. Constitutional tall stature comprises normal variants in which one or both parents are tall. Primary disorders may have a prenatal onset and may be of chromosomal or genetic origin. Secondary overgrowth syndromes are most often the result of hormonal disturbances. Height prediction plays a key role in the management of tall children. Prediction equation models have been developed based on the growth data of healthy tall children. There is general agreement that a favourable effect on reducing ultimate height is obtained using high doses of sex steroids (girls 100-300 microg ethinyloestradiol; boys testosterone (T) ester depot preparations 250-1000 mg/month), the height reduction being greater when the treatment is started at a lower chronological and/or bone age. An alternative is the induction of puberty with low doses of sex steroids (girls 5-50 microg ethinyloestradiol; boys T esters 25-50 mg/m2/3 wk). In addition orthopaedic procedures have been suggested, but there is limited experience. Although psychosocial factors constitute the main reason for treating tall stature, extensive psychological investigations before or during height limiting therapy are lacking. Moreover, there are no objective data indicating lifelong psychosocial damage resulting from being tall.     

Excessive growth

Tall stature and excessive growth syndrome are a relatively rare concern in pediatric practice. Nevertheless, it is important to identify abnormal accelerated growth patterns in children, which may be the clue in the diagnosis of an underlying disorder. We present a case of pituitary gigantism in a 2 1/2-year-old child and discuss the signs, symptoms, laboratory findings, and the treatment. Brief discussions on the differential diagnosis of excessive growth/tall stature have been outlined. Pituitary gigantism is very rare in the pediatrics age group; however, it is extremely rare in a child that is less than 3 years of age. The nature of pituitary adenoma and treatment options in children with this condition have also been discussed.     

Tentative evidence of Y-linked statural gene(s). Growth in the testicular feminization syndrome

The linear growth data of 48 XY individuals, presumed to be androgen-insensitive as a consequence of the testicular feminization syndrome, were found to be similar to normal male standards and tall for normal female standards. These data are interpreted as evidence for one or more Y-linked gene function(s) which augment stature independently of testosterone effects.     

Assessing tall stature

Children and adults are considered ‘tall’ when their height is above 98th centile for age i.e. 2 standard deviations (SD) above the mean. Tall stature is familial in most cases. In assessing children with tall stature the mid-parental height centile should always be calculated and this article gives advice on how to proceed with investigation and management for children who are unexpectedly tall. Other common causes of tall stature are obesity or early normal puberty. Precocious puberty, hyperthyroidism and GH excess are less common but these will also cause rapid height velocity at any age and precocious puberty should be excluded in every child presenting with tall stature. Where height centile exceeds mid-parental centile prediction it is helpful to look for genetic syndromes, metabolic conditions and sex chromosome abnormalities. Constitutional tall stature i.e. physiologically normal advanced growth and development is a diagnosis of exclusion and treatment is rarely required. Treatment options include early and accelerated induction of pubertal development with a physiological sex hormone regimen, or epiphysiodesis, but need to be considered before puberty onset. High dose sex steroids are no longer indicated.     

Difficulties in diagnosing Marfan's syndrome in childhood and adolescence

BACKGROUND: The diagnosis of Marfan's syndrome in childhood and adolescence is made by the criteria of the Gent nosology, which evaluates genetic data, family history and a spectrum of clinical criteria. Due to the age dependent manifestations of the clinical symptoms, combined with the extreme heterogeneity of Marfan's syndrome diagnosis in early childhood remains sometimes difficult. PATIENTS: Prospectively, we analyzed the clinical symptoms of all patients where Marfan's syndrome was suspected. We evaluated those patients between January 1997 and April 2002 by an interdisciplinary approach. METHODS: We compared the clinical datas of the patients by using the Gent nosology and the Berlin nosolgy. RESULTS: 34 patients underwent full follow-up. The median age was 10,32 years with a range of 0,01 to 37,31 years, 19 patients were male, 15 patients were female. In eight patients Marfan's syndrome could be rouled out, 9 of 26 patients (34,6 %) fullified the criteria of the Gent nosology, in 17 of 26 patients (65,4 %) Marfan's syndrome remained just suspected, but was not fullified by the criteria of the Gent nosology. Concerning the Berlin nosology 14 of 26 patients (53,8 %) fullified the criteria, 12 of 26 patients (46,2 %) failed. Due to the criteria of the Gent nosology 14 patients (53,8 %) fullified the criteria of skeletal involvement, 21 patients (80,8 %) fullified cardiovascular major manifestation, 6 patients (23,1 %) had an ophthalmic major manifestation, and 9 patients (34,6 %) had an affected first degree relative or were genetically determined. CONCLUSIONS: On the basis of the data of our patients the diagnosis of Marfan's syndrome in childhood and adolescence can be made more sensitive by the criteria of the Berlin nosology compared to the Gent nosology. This seems to be caused by the age dependent manifestations of the symptoms. Until diagnostic algorhythms of Marfan's syndrome in childhood remain suboptimal, continuous clinical follow-up for all cases even those only in the case of suspected Marfan's syndrome are necessary to exclude complicated course and to improve outcome.     

The spectrum of clinical paediatric endocrinology: 28 years of referrals to an individual consultant

Aim: To review referrals throughout the career of an individual paediatric endocrinologist. Methods: A retrospective cohort study in metropolitan clinics in Queensland analysed details of all 9062 patients aged <18 years referred between January 1980 and December 2007 to determine the proportion of diagnoses in major disease categories and changes in referral patterns over time. Results: Short stature (29%), type‐1 diabetes mellitus (20%) and pubertal disorders (12%) accounted for most cases, with thyroid disorders (7%), obesity (6%), tall stature (5%) and hypothalamic‐pituitary disorders (4%) the next commonest. An organic cause for short stature, early puberty, late puberty, tall stature and obesity was found in 39%, 32%, 19%, 15% and 6% of cases, respectively. Boys were more likely to present with short stature or delayed puberty, and girls with tall stature and early puberty. Substantially fewer boys than girls were diagnosed in infancy with congenital adrenal hyperplasia, suggesting that some may be dying undiagnosed. Comparisons between 1980 and 1984, and 2000–2004 revealed increases in the percentage of referrals for type‐1 diabetes mellitus (particularly in the young), early puberty, hypothalamic‐pituitary and bone disorders, and decreases in those for short and tall stature. Conclusions: Disorders of growth and puberty accounted for 52% of referrals and many have an organic cause. A neonatal screening programme for congenital adrenal hyperplasia is overdue. Changing attitudes to short and tall stature and a profound increase in new cases of diabetes mellitus indicate that substantially greater resources for treatment of childhood diabetes mellitus will be required in future.     

Tall stature as presenting symptom in a girl with triple X syndrome

An 11 year-old girl presented with 47,XXX karyotype. Our report emphasizes the fact that triple X syndrome has also to be considered in girls presenting with tall stature that is not explained by parental heights.     

Ventricular dysrhythmias in children with Marfan's syndrome

A teenager with Marfan's syndrome required resuscitation and was found to have multiform premature ventricular contractions and ventricular tachycardia. Of 24 children with Marfan's syndrome, eight (33.3%) were found to have ventricular dysrhythmias, including three with ventricular tachycardia. Six of these eight patients had mitral valve prolapse, and five had prolonged QT or QTU intervals corrected for heart rate. However, only two patients had severe mitral regurgitation, five had only mild heart disease, and one had no detectable heart lesion. The role of mitral valve prolapse and/or delayed repolarization in the development of ventricular dysrhythmia was explored. Delayed repolarization, especially when combined with mitral valve prolapse, is associated with occurrence of ventricular dysrhythmia. Serious ventricular dysrhythmia can occur in children with Marfan's syndrome with or without substantial valve disease, and the dysrhythmia appears to progress with age.     

Sotos syndrome presenting with epilepsy

A fourteen and a half year-old boy of tall stature presenting with epilepsy was diagnosed as having Sotos syndrome (cerebral gigantism) at the Hacettepe University Children's Hospital. Since EEG abnormalities are known manifestations in this syndrome, a case presenting with epilepsy is very rare. We believe that a presumed cerebral defect could create convulsions and would thus be the cause of cerebral gigantism whose etiology is still unclear. Thus patients with this syndrome should be followed up for the risk of epilepsy.     

Evolving phenotype of Marfan's syndrome

AIM: To examine evolution of the physical characteristics of Marfan's syndrome throughout childhood. METHODS: 40 children were ascertained during the development of a regional register for Marfan's syndrome. Evolution of the clinical characteristics was determined by repeat evaluation of 10 patients with sporadic Marfan's syndrome and 30 with a family history of the condition. DNA marker studies were used to facilitate diagnosis in those with the familial condition. RESULTS: Musculoskeletal features predominated and evolved throughout childhood. Gene tracking enabled early diagnosis in children with familial Marfan's syndrome. CONCLUSIONS: These observations may aid the clinical diagnosis of Marfan's syndrome in childhood, especially in those with the sporadic condition. Gene tracking has a role in the early diagnosis of familial Marfan's syndrome, allowing appropriate follow up and preventive care.