Growth charts for cri-du-chat syndrome: an international collaborative study

Low birth weight and slow growth are frequently observed in the patients with cri-du-chat syndrome. To provide a growth reference standard for children with cri-du-chat syndrome, syndrome-specific growth charts have been developed from a combination of cross-sectional and longitudinal measurements on 374 patients from North America, Italy, Australia, and the British Isles. The data were obtained from pediatric records, parent reporting, and personal examinations at national 5p- parent support group meetings in the U.S., Italy, U.K., and Australia. The growth curves include height and weight measurements for patients ages 0 to 18 years and head circumference measurements for patients ages 0 to 15 years. Birth weight was above the 5th percentile of general population in 50% of cases: mean weight 2.8 kg +/- 1.85 SD for males and 2.6 kg +/- 1.51 SD for females. Growth curve medians were usually at or below the 5th centile of reference populations throughout life. The median head circumference falls below the 2nd centile, and this change increases with age. The charts show that compared with the standard population, most children with cri-du-chat syndrome are small at birth and as they grow most, but not all, have significant microcephaly and compromised weight for age, and to a lesser extent, compromised height for age. Am. J. Med. Genet. 94:153-162, 2000.     

Growth charts for cri‐du‐chat syndrome: An international collaborative study

Low birth weight and slow growth are frequently observed in the patients with cri‐du‐chat syndrome. To provide a growth reference standard for children with cri‐du‐chat syndrome, syndrome‐specific growth charts have been developed from a combination of cross‐sectional and longitudinal measurements on 374 patients from North America, Italy, Australia, and the British Isles. The data were obtained from pediatric records, parent reporting, and personal examinations at national 5p‐ parent support group meetings in the U.S., Italy, U.K., and Australia. The growth curves include height and weight measurements for patients ages 0 to 18 years and head circumference measurements for patients ages 0 to 15 years. Birth weight was above the 5th percentile of general population in 50% of cases: mean weight 2.8 kg ± 1.85 SD for males and 2.6 kg ± 1.51 SD for females. Growth curve medians were usually at or below the 5th centile of reference populations throughout life. The median head circumference falls below the 2nd centile, and this change increases with age. The charts show that compared with the standard population, most children with cri‐du‐chat syndrome are small at birth and as they grow most, but not all, have significant microcephaly and compromised weight for age, and to a lesser extent, compromised height for age. Am. J. Med. Genet. 94:153–162, 2000. © 2000 Wiley‐Liss, Inc.     

Fetal biometry in the Brachmann-de Lange syndrome

The Brachmann-de Lange syndrome (BDLS) is diagnosed in children on the basis of a distinctive clinical phenotype which includes retarded physical growth. Because there are no genetic or biochemical tests at present, the antenatal detection of the syndrome may depend upon identification of some aspect of the phenotype in the fetus using ultrasound imaging. We studied the growth of 23 subsequently diagnosed fetuses with the BDLS using standard biometric parameters defined by prenatal ultrasound imaging. Sonographic studies were obtained through a national parents' group, the Cornelia de Lange Syndrome Foundation. Assessment of fetal growth was made using four standardized measurements: the biparietal diameter, head circumference, femur length, and abdominal circumference. These values were compared to established tables of normal fetal growth and established rations of fetal body proportions. The cross-sectional growth curve derived using all measurements collected as a composite group indicates that growth retardation would be first detected as early as 25 weeks. In five fetuses with measurements both before and after 25 weeks of gestation, longitudinal growth curves indicated that the diagnosis of “small for gestational age” would have been suggested between 20 and 25 weeks. The mean fetal weight estimates closely followed the fifth centile curve of normal fetuses both before and after 25 weeks. Cephalic indices in BDLS fetuses indicated either frank brachycephaly (25%), or were at the upper portion of the normal range. Femur lengths were relatively short (less than 90% of their expected length ) in 4 of the 11 fetuses where such information could be obtained. BDLS fetuses demonstrate early and symmetric intrauterine growth retardation. We conclude that fetal biometry can provide a valuable index in the assessment of a pregnancy suspected to be at risk for a severely affected BDLS child. © 1993 Wiley-Liss, Inc.     

Growth charts for individuals with Coffin‐Siris syndrome

Coffin‐Siris syndrome (CSS; OMIM #135900) is a rare, multisystem syndrome caused by pathogenic variants in genes encoding the BRG‐1 associated factors complex (BAF). Individuals with CSS often present with feeding difficulties and failure to thrive during infancy, in addition to a number of variable congenital anomalies. Nutritional interventions are used to support growth in this population, and growth hormone therapy has been reported in a limited number of cases. The purpose of this study was to construct CSS‐specific growth charts to better characterize the growth in this population. Anthropometric data were collected from 99 individuals enrolled in the CSS/BAF pathway international registry via a retrospective chart review. All measurements obtained after the first exposure to growth hormone therapy were excluded from this analysis. Sex‐specific centiles (5th, 50th, and 95th) were estimated for height, weight, and head circumference from birth to age 10. Cubic smoothing splines were then fit to the centile estimates and superimposed on normative male and female growth curves for comparison. The CSS patients in this cohort exhibited normal growth parameters at birth. By age 10, the weight and head circumference of the CSS cohort began to approach normal parameters. Stature, however, remained shortened at 10 years of age.     

Fragile X syndrome: growth, development, and intellectual function

We collected data on growth, psychomotor development, speech and language development, and intellectual function on a cohort of 100 males with the fragile X chromosome and 95 carrier females. The data include information on prenatal growth (33 males), growth during the preadult years (32 males), psychomotor development during the first 2 years (25 males), speech and language development (15 males and 5 females), and intellectual function (93 males, 33 females, and 10 obligate carriers who were cytogenetically normal). Birth measurements appeared normal when plotted on the Usher/McLean curves of newborn infants (mean head circumference - OFC - at 40th centile, length at 60th centile and weight at 55th centile). Following birth, OFC rose above the 50th percentile and continued above average throughout the preadult years, whereas average length was above average for the first 5 years only and weight did not deviate from the normal mean. Psychomotor development lagged behind the norm from birth with affected males requiring nearly twice as long as expected to sit alone, walk unassisted, and say first words clearly. All males and females studied had significant language delay; all except one male had abnormalities of articulation. All on whom a clear voice sample was obtained had low voice pitch, and 80% had a hoarse or harsh quality of voice. Five males had word repetitions or perseverative speech during the preadult years. The mean IQ of the 93 males studied was 33 and regression analysis demonstrated a decrease in intellectual performance with age. Four fifths of the female carriers who expressed the fra(X) had intellectual performance in the mentally retarded range and showed similar decrease in performance with age. Obligate female carriers who did not express the fra(X) site had normal IQs (IQ 102 +/- 13.3).     

De Lange syndrome: subjective and objective comparison of the classical and mild phenotypes.

Classical de Lange syndrome presents with a striking face, pronounced growth and mental retardation, and variable limb deficiencies. Over the past five years, a mild variant has been defined, with less significant psychomotor retardation, less marked pre- and postnatal growth deficiency, and an uncommon association with major malformations, although mild limb anomalies may be present. We have evaluated 43 subjects with de Lange syndrome, 30 with classical features, aged from birth to 21 years, and 13 with the mild phenotype, aged from 18 months to 30 years. In addition to assessment of gestalt and facial change with time, detailed craniofacial measurements have been obtained on each subject and composite pattern profiles compiled. The characteristic face of classical de Lange syndrome is present at birth and changes little throughout life, although there is some lengthening of the face with age and the jaw becomes squared. In mild de Lange syndrome, the characteristic classical appearance may be present at birth, but in some subjects it may be two or three years before the typical face is obvious. In general, the overall impression is less striking, perhaps because of increased facial expression and greater alertness. With age, the face loses the characteristic appearance, the nasal height increases, the philtrum does not seem as long, and the upper vermilion is full and everted, although the crescent shaped mouth with downturned corners remains. Eyebrows may be full and bushy. Objective comparison of the face in mild and classical de Lange syndrome, through the use of craniofacial pattern profiles, shows marked similarity of patterns at 4 to 9 years; both groups have microbrachycephaly, but the individual dimensions of the mild group are slightly closer to normal than their classical counterparts. The correlation coefficient is high (0.83). In the adult groups, similarity of patterns remains but is less marked. The normalisation of scores in the mild group is more dramatic. The correlation coefficient is lower (0.71). These objective findings substantiate clinical impressions of a phenotypic dichotomy. Early in life, the craniofacial features in mild de Lange syndrome may be indistinguishable from the classical phenotype and alternative discriminators must be sought in order to identify those subjects in whom the prognosis is more optimistic. Birth weight of more than 2500 g and absence of major limb anomalies may help in this regard.     

Growth pattern in the Apert syndrome

In this paper, we demonstrate that a discernible and unique growth pattern characterizes the Apert syndrome. The keys to understanding Apert newborn measurement values are brain size and cranial configuration. Both true megalencephaly and coronal synostosis are present at birth. Thus, the head is unusually heavy and the cranium is disproportionately high. Mean newborn length and weight are above the normal 50th centile. Of our newborn patients, 16% exceeded 4,000 g in weight. Preterm infants were appropriate or slightly large for gestational age. A biphasic linear growth pattern was found. In childhood, deceleration of linear growth occurs so that most values fall between the 5th and 50th centiles. From adolescence to adulthood, deceleration becomes more pronounced. This 2-step linear growth deceleration results in large measure from rhizomelic shortness of the lower limbs. Puberty takes place within the normal time frame. Although a disproportionate amount of the megalencephaly accounts for the dramatic increase in head height, the widely patent midline calvarial de fect, allowing the brain to expand anteriorly into the metopic area, and some increase in the head breadth permit the mean head circumference at birth to normalize slightly above the 50th centile. During the growth period, the head circumference was studied in surgically unoperated Apert patients from the 1960s and earlier. The natural history of the growing cranium consists of gradual deceleration in head circumference from slightly above the 50th centile at birth to within or at ?2 SD later on. © 1993 Wiley-Liss, Inc.     

Head circumference of children with Williams-Beuren syndrome

Head circumference is considered an important parameter of brain growth and development. Syndrome-specific standards for head circumference in Williams-Beuren syndrome (WBS) are not available to date, although mental retardation is a leading manifestation in the syndrome. Therefore, we investigated head growth in 63 girls (251 measurements) and 88 boys (298 measurements) with WBS between birth and adulthood. Most measurements in both sexes were from the first 4 years of life (n = 162 in girls and n = 189 in boys). Mean (±SD) head circumference at birth was 33.39 ± 1.38 cm and 34.02 ± 1.44 cm for term girls and boys, respectively. Although head growth in WBS girls and boys was at a slower velocity, the pattern of head circumference was similar to that in the normal population. After the age of 3 months, head circumference started to fall below the normal mean in girls (0.5–2 cm). In boys, mean head circumference was below the normal mean already at 1 month of age (2 cm). The deficit increased to 3 cm from 6 months to 4 years. Adult OFC was 52.85 ± 1.75 cm (n = 16) compared to 55.70 ± 1.83 cm (n = 46; P < 0.00001) in WBS women and 55.51 ± 1.68 cm (n = 30) compared to 57.87 ± 1.29 cm (n = 31; P < 0.00001) in WBS men. During development, microcephaly is only seen in about one third of WBS patients. © 1994 Wiley-Liss, Inc.     

Growth from birth to two years of rich urban and poor rural Iranian children compared with Western norms

1.Length, weight and head circumference were measured from birth to age 2 in 63 boys and 68 girls of a high-income Iranian group living in Shiraz in economic and cultural conditions similar to high income groups in Western Europe and North America. The 10th, 50th and 90th centiles of the measurements were very similar to the London and Boston standards.

2.The high-income Iranian group was compared with racially similar village and poor urban groups in Shiraz and the nearby countryside. The 50th centiles of these groups for length and weight were at or below the 3rd centile of the high-income group from 3 to 24 months; head circumference 50th centile was at the 10th to 3rd centile.

3.It is concluded that the growth potential of Iranian children is no less than that of West Europeans, though the majority of the population grow along a very much lower curve.     

Non-parametric estimation of age-related centiles over wide age ranges

A new method for estimating age-related centile curves has been developed, which is suitable for measurement covering a wide age range. The method was used to calculate weight centile curves of 8995 children from birth to 6 years obtained by the Collaborating Centre for Physical Growth and Psychosocial Development of Children in Shanghai, China.     

Clinical features in 27 patients with Angelman syndrome resulting from DNA deletion.

We report the clinical features in 27 Australasian patients with Angelman syndrome (AS), all with a DNA deletion involving chromosome 15(q11-13), spanning markers from D15S9 to D15S12, about 3 center dot 5 Mb of DNA. There were nine males and 18 females. All cases were sporadic. The mean age at last review (end of 1994) was 11 center dot 2 years (range 3 to 34 years). All patients were ataxic, severely retarded, and lacking recognisable speech. In all patients, head circumference (HC) at birth was normal but skewed in distribution, with 62 center dot 5% at the 10th centile. At last review HC was around the 50th centile in three patients (12 center dot 5%) while 15 had poor postnatal head growth. Short stature was not invariable, 5/26 (19%) were on or above the 50th centile. Hypotonia at birth was recorded in 15/24 (63%) and neonatal feeding difficulties were recorded in 20/26 (77%). Epilepsy was present in 26/27 (96%) with onset by the third year of life in 20 patients (83%). Improvement in epilepsy was reported in 11/16 patients (69%) with age. An abnormal EEG was reported in 25/25 patients. Hypopigmentation was present in 19/26 (73%). One patient had oculocutaneous albinism. Five patients could not walk independently. Of the remaining 22 who could walk, age of onset of walking ranged from 2 to 8 years. Disrupted sleep patterns were present in 18/21 patients (86%), with improvement in 9/12 patients (75%) over 10 years of age. The clinical features in this group of deletional AS patients were similar to previous reports, but these have not separated patients into subgroups based on DNA studies. In our group of deletional cases, 100% showed severe mental retardation, ataxic movements, absent language, abnormal EEG, happy disposition (noted in infancy in 95%), normal birth weight and head circumference at birth, and a large, wide mouth. These features occurred with a higher frequency than in AS patients as a whole. Our study also provided information on the evolution of the phenotype. The data can act as a benchmark for comparisons of AS resulting from other genetic mechanisms.     

Neurofibromatosis type 1 growth charts

Growth abnormalities such as macrocephaly and short stature have been described and are considered a consistent finding in neurofibromatosis type 1 (NF1), one of the most common autosomal dominant disorders in man. We present here a clinical study on the growth profile of a sample of NF1 patients collected through a population-based registry that covers three contiguous regions of North-East Italy (NEI-NF Registry). Auxometric traits of 528 NF1 patients have been measured with the aim of drawing growth charts for height, weight, and head circumference (OFC). Height velocity charts were based on a subset of 143 children who underwent multiple measurements. No differences in height were apparent between NF1 and normal subjects up to age 7 (girls) and 12 (boys) years; subsequently, the 50th centile of NF1 subjects tends to overlap with the 25th centile of normal subjects, and the 3rd centile is much lower in NF1 subjects than in normal subjects, mainly during adolescence. The negatively skewed distribution of height seems to indicate that height growth impairment affects only a proportion of NF1 subjects; height growth impairment does not seem related to disease severity. As for weight, our data suggest that slight overweight is a characteristic of adult NF1 subjects (mainly among males), independent of disease severity. Height growth velocity is normal during childhood for both sexes, whereas the pubertal spurt is slightly anticipated and reduced in NF1 boys but not in girls. Our data confirm previous observations that macrocrania affects most NF1 subjects; the shape of the head growth curve is similar in NF1 and normal girls, whereas NF1 boys present an OFC pubertal growth spurt much more pronounced and delayed than normal boys. The disproportion between OFC and height seems to be related to disease severity in boys but not in girls. Growth charts presented here can be useful in neurofibromatosis clinics for the identification of the effects of secondary growth disorders, for growth prognosis, and for the evaluation of the effects of a therapy such as GH therapy after radiotherapy for optic glioma.     

Anthropometric study with emphasis on hand and foot measurements in the Prader-Willi syndrome: sex, age and chromosome effects

Age, sex and chromosome effects on weight, height, sitting height, three head dimensions, and five hand and three foot measurements were analyzed from 57 patients (35 males and 22 females) with the Prader-Willi syndrome (PWS). No significant differences were observed in anthropometric data between PWS patients with the 15q chromosome deletion and those with normal chromosomes. Preschool children were found to have dolichocephaly, while hand and foot measurements, stature and sitting height were within normal range, although foot size was smaller than hand size in females when compared with PWS males. However, anthropometric measurements, excluding weight, head length and ankle breadth, were less than -2 SD in adult patients. Abnormal growth patterns apparently exist with significant negative correlations with age, particularly in PWS males, for height, sitting height, head circumference, and hand and foot measurements, but a significant positive correlation for weight was found in patients below 10 years of age.     

Macrocephaly, epilepsy, autism, dysmorphic features, and mental retardation in two sisters: a new autosomal recessive syndrome?

We report two sisters with macrocephaly, epilepsy, and severe mental retardation. The first child was a 14 year old girl born at term after a normal pregnancy, with birth weight 3600 g and occipitofrontal circumference (OFC) 36 cm (75th centile). Her head size increased markedly during the first six months of life, and was later stable at 2-3 cm above the 97.5th centile. Her development was characterised by psychomotor delay, epilepsy, and autistic features. Her face appeared mildly dysmorphic with a large forehead, short philtrum, and bushy eyebrows. Her younger sister was also born at term with birth weight 2600 g and OFC 34 cm (25th centile). She also developed postnatal macrocephaly with OFC 2 cm above the 97.5th centile and the same mild dysmorphic facial features as her sister. Her development was also characterised by psychomotor delay, autistic features, and epilepsy. In addition, she suffered from coeliac disease. She died unexpectedly at the age of 5 years, probably from an epileptic attack. Necropsy confirmed megalencephaly but no other pathological changes were found. The clinical features in these two sisters do not fit with any known syndrome and may represent a previously unrecognised autosomal recessive disorder.     

Leg length,sitting height,and body proportions references for achondroplasia: New tools for monitoring growth

Achondroplasia is the most common form of inherited disproportionate short stature. We report leg length, sitting height, and body proportion curves for achondroplasia. Seven centile format of sitting height, leg length, sitting height/leg length ratio, sitting height/height ratio, and head circumference/height ratio were estimated by the LMS method. The Q‐test was applied to assess the goodness of fit. For comparison, centiles of sitting height and leg length were graphed using Argentine national growth references for achondroplasia and non‐achondroplasia populations. The sample consisted of 342 children with achondroplasia (171 males, 171 females) aged 0–18 years. The median (interquartile range) number of measurements per child was 6 (3, 12) for sitting height and 8 (3, 13) for head circumference. Median leg length increased from 14 cm at age 1 week to 44 and 40 cm (males and females, respectively) in achondroplasia adolescents which is 3.5 cm shorter than non‐achondroplasia children at age 1 week and, 38 cm shorter at adolescence. Median sitting height increased from 34 cm at birth to 86 and 81 in adolescents’ boys and girls respectively, only 5 cm shorter than non‐achondroplasia children. Sitting height/leg length decreased from 2.61 at birth to approximately 1.90 at adolescent. Median head circumference/height ratio decreased from 0.79 at birth to 0.46 at 18 years in both sexes. Growth of lower limbs is affected early in life and becomes more noticeable throughout childhood. The disharmonic growth between the less affected trunk and the severely affected limbs determine body disproportion in achondroplasia.

     

Brachmann-de Lange syndrome with normal IQ

The Brachmann-de Lange syndrome is a disorder with a high degree of clinical variability, generally associated with moderate to severe mental retardation. To date, 7 previous cases of Brachmann-de Lange syndrome with normal intelligence (IQ > 70) have been described. We report the eighth case of Brachmann-de Lange syndrome with normal intelligence. In reviewing thr literature, consistent clinical menifestations seen in these 8 patients that are of prognostic value are the absence of significant limb anomalies and birth weight > 2,500 g. © 1993 Wiley-Liss, Inc.     

Down syndrome birth weight in England and Wales: Implications for clinical practice

The aim of this study was to determine if syndrome‐specific birth weight charts were beneficial for babies with Down syndrome in England and Wales. Birth weights of 8,825 babies with Down syndrome born in England and Wales in 1989–2010 were obtained from the National Down Syndrome Cytogenetic Register. Birth weight centiles for 30–42 weeks gestation by sex were fitted using the LMS method and were compared to those for unaffected babies from the UK‐WHO growth charts. For babies born with Down syndrome the median birth weight from 37 to 42 weeks was 2,970 g (10th–90th centile: 2,115–3,680) for boys and 2930 g (2,100–3,629) for girls, and the modal age of gestation was 38 weeks, 2 weeks earlier than for unaffected babies. At 38 weeks gestation they were only slightly lighter than unaffected babies (159 g for boys and 86 g for girls). However at 40 weeks gestation the shortfall was much greater (304 g and 239 g, respectively). In neonates with Down syndrome there is little evidence of growth restriction before 38 weeks gestation, so up to this age it is appropriate to use the UK‐WHO birth weight charts. Thereafter birth weight is below that of unaffected babies and it should be plotted on the UK Down syndrome growth charts. © 2015 The Authors. American Journal of Medical Genetics Part A Published by Wiley Periodicals, Inc.     

Twins: measures of birth size at different gestational ages

Means, standard deviations, and empirical centile values are given for birth weight, length and head circumference for twins born at gestational ages 31+ to 42+ weeks. The data are compared with recent results for singletons, and the twins show a deficit that becomes greater as gestational age increases. Although weight may be slightly more affected than the other two measures, the relative growth suppression for twins is quite similar in all three dimensions. Comparatively, the average size of twins born at 33+ weeks gestational age is equal to the 36th centile for singletons; but at 40+ weeks gestational age, the average size for twins is below the 5th centile for singletons.     

Growth and maturation in Marfan syndrome

Understanding the growth pattern in Marfan syndrome is important for prediction of expected growth, prevention of excessive growth by hormone therapy, timing of surgical epiphysiodesis for cessation of growth, and instituting brace treatment for scoliosis. In this study, we analyze growth patterns and generate growth charts for persons with Marfan syndrome. From the charts of 180 clinically diagnosed Marfan patients, longitudinal height and weight measurements were obtained. From this data, growth charts and growth velocity charts were generated for males and females. Skeletal maturation was studied by determining the Risser signs from the x-rays of 71 males and 56 females. From 22 female patients, age of menarche was available and retrieved either by reviewing the charts or contacting the patients. Mean length at birth was 53 +/- 4.4 cm for males and 52.5 +/- 3.5 cm for females. Mean final height was 191.3 +/- 9 cm for males and 175.4 +/- 8.2 cm for females. Mean birth weight was 3.51 +/- 0.74 kg for males and 3.48 +/- 0.68 kg for females. The puberty-associated peak in growth velocity was 2.4 years earlier than the gender-matched general population for males with Marfan syndrome and 2.2 years earlier for females. Age of menarche was 11.7 +/- 2 years of age, which is also early compared to the general population. This study suggests that the growth spurt and pubertal skeletal maturation occur early in Marfan syndrome. The growth curves generated should help more accurately predict adult stature, as well as monitor progression toward it.     

The hand profile on de Lange syndrome: diagnostic criteria.

The hand pattern profiles of 18 previously published and 10 new cases of de Lange syndrome were compared to those of cases referred as suspects, but judged clinically and by numerical taxonomic methods not to have de Lange syndrome (non-de Lange). Based on a Poznanski metacarpophalangeal profile of the 2 groups of patients, a simple scoring system using 11 measurements was devised using the 16 most marked differences within and between metacarpals and phalanges. Of the metacarpals, the first is shorter than the second, third, fourth, or fifth; and the second and fifth are shorter than the third or fourth. Of the middle phalanges, the third and fourth are shorter than the respective metacarpal and than the second and fifth middle phalanx. Of the distal phalanges, the fifth is shorter than the second. The mean Z score for these 11 measurements is further below normal in the de Lange group than in the non-de Lange group. All 11 non-de Lange patients had a score less than 17, and all 28 de Lange patients had a score of 18 or more.