doi: 10.1016/S0022-3476(95)70347-0, 12. Mentzel HJ, Vilser C, Eulenstein M, Schwartz T, Vogt S, Bottcher J, et al. [2], In the United States, bone age is usually determined by comparing an x-ray of the patient's left hand and wrist to a set of reference images contained in the Greulich and Pyle atlas. doi: 10.1093/bmb/lds014. Br J Sports Med. J Pediatr. Hand Bone Age. Peak height velocity (PHV) occurs at the average age of 11 years for girls and at the average age of 13 years for boys. Eur J Endocrinol. New technology for bone age determination includes computer-automated readings and assessments obtained from alternative imaging modalities. (2015) 16:2015. There is a chart for males and another for females with possible bone ages ranging from 1 month to 5 years. 5. As kids grow, their growth plates look thinner on X-rays and eventually disappear (called "closed growth plates"). In multiple linear regression analysis, advanced bone age was most strongly associated with higher Tanner stage of sexual development, and higher weight, height or BMI percentile. doi: 10.1159/000184848, Keywords: skeletal development, height, X ray, children, bone age, Citation: Cavallo F, Mohn A, Chiarelli F and Giannini C (2021) Evaluation of Bone Age in Children: A Mini-Review. Degree of a person's skeletal development, Evaluation of the bones of the hand and wrist. p. 293753. Bol Med Hosp Infant Mex. doi: 10.1111/j.1754-4505.2008.00020.x. Skeletal maturation in children with Cushing syndrome is not consistently delayed: the role of corticotropin, obesity, and steroid hormones, and the effect of surgical cure. In the latest episode of our podcast series, Jessica L. Peck, DNP, APRN, CPNP-PC, CNE, CNL, FAANP, FAAN shares why she got into medicine, the myths of pediatric, and what the future may hold for the specialty. doi: 10.1002/1520-6300(200009/10)12:5<610::AID-AJHB5>3.0.CO;2-D. 82. To note, usually the first ossification center to appear is in the contest of Capitate and Hamate at the second month in females and around the fourth month in males. Evaluation may also be needed in a child who has a normal height, but a projected height more than two standard deviations from the midparental height. Bone age may be used either in normal variants of delayed growth patterns with delayed puberty and accelerated growth patterns with early puberty, where it may be more consistent with height age and adult height prediction may be more consistent with genetics. It is based on a computerized system obtained from a series of measurements provided by a large reference population. Woods CP, Argese N, Chapman M, Boot C, Webster R, Dabhi V, et al. According to a recent study, the BoneXpert method is affected by obesity to a lesser extent than the GreulichPyle method. (2007) 51:5003. Loder RT, Estle DT, Morrison K, Eggleston D, Fish DN, Greenfield ML, et al. Pediatrics. (2016) 170:16370. Spec Care Dentist. In order to achieve a greater accuracy and diagnostic reproducibility, it is important that bone age determination has the lowest intra- and interoperator variability. Nemours Children's Health and KidsHealth are registered trademarks of The Nemours Foundation. World Health Organization growth charts should be used for children younger than two years, and the Centers for Disease Control and Prevention growth charts should be used for children older than two years. 4. After puberty, all carpals, metacarpals, and phalanges are completely developed, their physes are closed, and the assessment of skeletal maturity is based on the degree of epiphyseal fusion of the ulna and radius (8082). Puberty usually occurs early, leading to a near-normal height.19, Obese children are tall for their age.19 However, these children often have an early onset of puberty and therefore a near-normal final height.20, Intervention is usually not needed in children with tall stature. De Sanctis V, Soliman AT, Di Maio S, Bedair S. Are the new automated methods for bone age estimation advantageous over the manual approaches? Currently, hand and wrist X-ray is the gold standard to assess children's bone age. doi: 10.1016/j.forsciint.2014.02.030. This software is validated for different ethnic groups and for children with different endocrine disorders (132134). The images obtained by hand and wrist X-ray reflect the maturity of different bones. Further, there can be moderate levels of variability in the bone ages assigned to the same patient by different assessors. Buken B, Safak AA, Yazici B, Buken E, Mayda AS. Satoh M. Bone age: assessment methods and clinical applications. Nat Rev Endocrinol. Discussion. In this study of prepubertal children with and without obesity and/or PA, obesity was highly associated with BA advancement. doi: 10.1016/S0022-3476(78)81071-3, 139. [42][43] The bones of the limbs form and lengthen through endochondral ossification beginning by the 12th week after fertilization.[41]. The image in the reference atlas that most closely resembles the patient's x-ray is then used to assign a bone age to the patient. J Pediatr. (2004). (2010) 126:93844. Vignolo M, Milani S, DiBattista E, Naselli A, Mostert M, Aicardi G. Modified Greulich-Pyle, Tanner-Whitehouse, and Roche-Wainer-Thissen (knee) methods for skeletal age assessment in a group of Italian children and adolescents. Bone age in the 21st century: is Greulich and Pyle's atlas accurate for Israeli children? For infants and toddlers, weight, length, and head circumference should be plotted on a growth curve at every visit. doi: 10.1016/j.ajodo.2006.07.037, 99. A small amount of spinal growth concludes an adolescent's growth. For specific medical advice, diagnoses, and treatment, consult your doctor. This determination is based on the presence of particular centers of bone formation as well as the dimension and structure of the bones (3, 58). Bone age (BA) is a measure of the skeletal maturity of an individual and tells us about the growth potential of a child. Therefore, the bone maturation process can be better characterized by the evaluation of the knee region in children under the age of 3, while in those older than 3 years, the assessment of hand and wrist bones is the most appropriate (8082). Medical, statistical, ethical and human rights considerations in the assessment of age in children and young people subject to immigration control. Short or tall parents may themselves have a pathologic reason for their height, especially if they are more than two standard deviations from the adult norm.68, Growth velocity is a measurement of growth rate. (1975) 64:8538. Harel S, Hursh BE, Chan ES, Avinashi V, Panagiotopoulos C. Adrenal suppression in children treated with oral viscous budesonide for eosinophilic esophagitis. In a study conducted by King and collaborators in which bone aging was performed by three different operators using either GP or TW method, there was a significant intraindividual variability with values equal to 0.96 and 0.74 years, respectively (94). Pearson's correlation analysis revealed that was strong . Growth Horm IGF Res. [17][20] Finally, only the wrist and hand are imaged out of a desire to minimize the amount of potentially harmful ionizing radiation delivered to a child. Bone age advancement in prepubertal children with obesity and premature adrenarche: possible potentiating factors. (2006) 29:2416; discussion 8690. During this stage of development, the ossification centers for the epiphyses increase in width and thickness, becoming as wide as the metaphyses. As well, height prediction methods might be affected by ethnicity-related differences, thus either underestimating or overestimating adult height, with wide variations in accuracy. In addition, children with PA appeared to be affected by a BA . Multiple regression equations for predicting the adult height of boys and girls from height and bone age at ages 4 and upwards are presented. Introduction. The bones on the X-ray image are compared with X-rays images in a standard atlas of bone development, which . Girls: 8 to 12 cm (3 to 5 in) Boys: 10 to 14 cm (4 to 6 in) However, in children with certain conditions (e.g., growth hormone deficiency), normal . [2][5], To assign a bone age to the patient under review, a radiologist compares the patient's hand and wrist x-ray to images in the Greulich and Pyle atlas. Among the different procedures proposed, BonAge system represents an ultrasound machine that includes a probe connected to a main unit. Children with familial short stature or idiopathic short stature have a bone age equivalent to their chronologic age, and children with constitutional delay of growth and puberty or endocrine disorders have a bone age that is less than their chronologic age. The bibliographies of review articles and textbook chapters were also reviewed for original research articles. FCa has written the first draft of the manuscript. (1994) 331:62936. (2010) 7:26674. Thodberg HH, Kreiborg S, Juul A, Pedersen KD. 93. Congenital adrenal hyperplasia. doi: 10.1002/ajhb.1310010413, 125. Moreover, according to recent studies, BoneXpert computer-automated bone age determination method showed a significant positive correlation with chronological age and GreulichPyle. 78. Arch Dis Child. doi: 10.1016/0197-0070(87)90048-9, 84. The height age (HA) refers to the CA at which a child's height would be at the 50th percentile for age and sex. defects in bone mineralization process (commonly found in osteochondrodysplasia). All rights reserved. (1996) 45 Suppl 2:535. (2019) 49:118591. J Obstet Gynaecol Res. Tanner JM. The middle finger axis should be in line with the forearm axis, and the center of the X-ray tube should be over the distal end of the third metacarpus. Softer body tissues, such as the skin and muscles, allow the X-ray beams to pass through them. Garn SM, Rohmann CG. 1988, $57.50. (2014) 12:2005. doi: 10.1016/j.legalmed.2011.01.004, 123. doi: 10.1016/S0022-3476(52)80205-7, 138. N Engl J Med. (1973) 83:2336. Not only hormones but also gender might affect this process. Every 6-12 months, height and bone age should be assessed. Many devices approved for pediatric use were not tested in a clinical trial involving children. Meet the board: Jessica L. Peck, DNP, APRN, CPNP-PC, CNE, CNL, FAANP, FAAN. Intestinal inflammatory chronic conditions. In children, bone age serves as a measure of physiological maturity and aids in the diagnosis of growth abnormalities, endocrine disorders, and other medical conditions. 3rd ed. doi: 10.1093/ajcn/36.3.527, 27. Any child with bone age more than 2 years advanced or delayed, or whose growth pattern deviates from their genetic potential should bereferred to endocrinology for assessment, she noted. Therefore, chronological age differs from bone age, so the two indexes need to be distinguished: chronological age is defined as the age in years between birth and the evaluation of a subject; bone age is defined by the age expressed in years that corresponds to the level of maturation of bones. The bone ages of hand and elbow were different at puberty, and the elbow was a more reliable location for bone-age assessment at puberty. [1][2][3] As a person grows from fetal life through childhood, puberty, and finishes growth as a young adult, the bones of the skeleton change in size and shape. doi: 10.1016/j.jpeds.2013.11.065, 23. (1994) 7:1415. The Pediatric Endocrine Society website was searched for consensus statements and clinical guidelines. Then, the remaining centers progressively appear (Figure 1) (80). (1978) 93:74955. 106. p. 70932. Author disclosure: No relevant financial affiliations. However, bone age itself cannot be considered the only absolute and incontrovertible datum to define the chronological age (6879); therefore, limits and accuracy of this examination in predicting chronological age, especially in relation to different ethnic groups and underlying diseases, need to be considered. Correlation of bone age, dental age, and chronological age in survivors of childhood acute lymphoblastic leukaemia. 5 to 5.5 cm (2 to 2.2 in) Pubertal growth spurt. These methods differ according to the technique of the procedure and particularly to peculiar advantages and disadvantages (Table 1). Assessment of bone age is often required during international immigration programs (68, 69). Aicardi G, Vignolo M, Milani S, Naselli A, Magliano P, Garzia P. Assessment of skeletal maturity of the hand-wrist and knee: a comparison among methods. doi: 10.1111/j.1365-263X.2007.00892.x, 39. Springfield, IL: Blackwell Scientific Publications (1962). Although this method is very accurate and allows doctors to estimate children's bone age even when they are <1 year old, the Fels method is too complex, thus minimizing its daily use. doi: 10.1530/EJE-15-0608, 60. Recent studies show that organs like the liver can also be used to estimate age and sex, because of the unique feature of liver. London: Academic Press (1983). 1995-2023. Horm Res. [4] Other uses of bone age measurements include assisting in the diagnosis of medical conditions affecting children, such as constitutional growth delay, precocious puberty, thyroid dysfunction, growth hormone deficiency, and other causes of abnormally short or tall stature. Thereafter, the pisiform and the sesamoid become recognizable. The next version (TW3) takes into consideration only RUS bones, and it can be used through a software. Braz Oral Res. A boy has reached 99% of his adult height at a bone age of 17 years and has a small amount of height growth left from this point on. These changes can be seen by x-ray and other imaging techniques. King DG, Steventon DM, O'Sullivan MP, Cook AM, Hornsby VP, Jefferson IG, et al. Acta Radiol. 90. Medical treatment, either oral or dermal, can affect pubertal effects on bone age. doi: 10.1111/j.1365-2265.2010.03799.x, 33. Forensic Sci Int. In Italy, a multidisciplinary approach is suggested to evaluate bone age using the GreulichPyle TW3 methods for a complete characterization of chronological age of the refugee. Khan K, Elayappen AS. We did online searches of The New England Journal of Medicine, Pediatrics, American Family Physician, Pediatrics in Review, and the British Medical Journal to identify additional relevant articles. 2015;24(4):143-152. doi:10.1297/cpe.24.143. [16][22] The TW methods consist of evaluating individual bones and assigning a letter grade to each bone based on its degree of maturation. William Walter Greulich and Sarah Idell Pyle published the first edition of their standard reference atlas of x-ray images of the left hands and wrists of boys and girls in 1950. GH treatment and its effect on bone mineral density, bone maturation and growth in short children born small for gestational age: 3-year results of a randomized, controlled GH trial. (1982) 52:88112. doi: 10.1038/oby.2010.305, 51. This system allows the computer to perform reading operations. Chronological age and bone age were 8.7 4.0 and 8.8 4.3 years, respectively, for the entire population. Clin Immunol. A bone age study helps doctors estimate the maturity of a child's skeletal system. 69. This method is very simple and fast, needing roughly 1.4 min for the evaluation (10, 107), thus explaining why it is preferred by 76% of pediatric endocrinologists and radiologists (10). (2003) 349:77688. However, data obtained from the assessment of bone age can be widely used both in medical or nonmedical settings. (2010) 23:85561. These images were performed in 355 male and 322 female children born between 1928 and 1974, from the first month of life up to the age of 22 years (124). It is a safe and painless procedure that uses a small amount of radiation. doi: 10.1001/archpedi.1993.02160360071022, 96. Instead, the variability among different operators (intervariability) is defined by the degree of variability in the interpretation of same data made by two different operators at the same time. 104. J Pediatr Endocrinol. [36], Bone maturation is delayed with the variation of normal development termed constitutional delay of growth and puberty, but delay also accompanies growth failure due to growth hormone deficiency and hypothyroidism.[37][38]. Bone age assessment: a large scale comparison of the Greulich and Pyle, and Tanner and Whitehouse (TW2) methods. ( p =0.67). doi: 10.3923/pjbs.2009.702.706. (2012) 102:1742. In many European countries, the increase in illegal immigration and above all the immigration of children and adolescents unaccompanied by parents and without identity documents posed important doubts and stressed the need for new procedures aimed at ensuring a better assistance and protection for young people. [7][8][16], The two most common techniques for estimating bone age are based on a posterior-anterior x-ray of a patient's left hand, fingers, and wrist. Bone age may be affected by several factors, including gender, nutrition, as well as metabolic, genetic, and social factors and either acute or chronic diseases, including endocrine dysfunction (39). Pediatr Res. Pinhas-Hamiel O, Benary D, Mazor-Aronovich K, Ben-Ami M, Levy-Shraga Y, Boyko V, et al. Zachmann M, Sobradillo B. Bayley-Pinneau, Roche-Wainer-Thissen, and Tanner height predictions in normal children and in patients with various pathologic conditions. Nemours Kids Health. Magiakou MA, Mastorakos G, Oldfield EH, Gomez MT, Doppman JL, Cutler GB, et al. A difference between a child's bone age and their chronological age might indicate a growth problem. doi: 10.1007/s00247-004-1385-3, 136. Vaska AI, Benson J, Eliott JA, Williams J. Your body age is a measure of how healthy and typical your physical condition is compared to what is expected for your chronological age. Moradi M, Sirous M, Morovatti P. The reliability of skeletal age determination in an Iranian sample using Greulich and Pyle method. Advanced bone age and hyperinsulinemia in overweight and obese children. (TW 2 method). (1998) 13:5007. Effect of a gluten-free diet on bone mineral density in children with celiac disease. Few pediatric devices were approved after a clinical trial involving children. Age, height, weight, BMI z-score, and BA/CA were similar in the PA and control groups . A renal anomaly? In the case of too much growth hormone, a child may have a bone age that is older than their chronological age suggesting that they are growing abnormally fast. [24] Then, a radiologist counts the number of ossification centers present and uses a chart to convert the sum of ossification centers to a bone age. (2000) 94:2128. Children with short stature and no identified cause and children with certain other identifiable causes of short stature should be referred to a pediatric endocrinologist. Other causes include renal, hepatic, and gastrointestinal diseases, and other genetic syndromes.1015, The initial evaluation of short stature (Figure 1) should include a history and physical examination, accurate growth assessment, calculation of the growth velocity and midparental height, and radiography to evaluate bone age.16 Drugs known to cause short stature include steroids (chronic use), attention-deficit/hyperactivity disorder medications, and anticonvulsants. Consequently, when a naturally short child has an advanced bone age, it stunts their growth at an early age leaving them even shorter than they would have been. (1988) 77:15460. Most children with short or tall stature have normal variants of growth. Bergeron MF, Bahr R, Bartsch P, Bourdon L, Calbet JA, Carlsen KH, et al. Several endocrine diseases might induce changes in bone age (10). A person viewing it online may make one printout of the material and may use that printout only for his or her personal, non-commercial reference. 7. (2010) 13:35560. doi: 10.1136/bjsports-2012-091296. A comparison of radiation dose of two strategies for skeletal age estimation", "Bone age assessment of children using a digital hand atlas", "Traditional and New Methods of Bone Age Assessment-An Overview", "Book Review: Skeletal Maturity. This test is usually ordered by pediatricians or pediatric endocrinologists. These systems use different algorithms; thus, no standardized and universally accepted indexes have been proposed so far (130, 131). Clin Pediatr Endocrinol. Tall stature is defined as a height more than two standard deviations above the mean for age (greater than the 97th percentile). [39] Liver weight increases with age and is different between males and females. A score is assigned to each bone based on maturation and sex of the patient. Of these, 5477 participants (2975 female [54.3%]) had bone measurements from at least 1 age after peak height velocity . London. In clinical trials, the most common adverse reactions involved the implant site and included discomfort, bruising, soreness, pain . Olesen T, Egeblad M, Dige-Petersen H, Ahlgren P, Nielsen AM, Vesterdal J. Somatic manifestations in children suspected of having been maltreated. Stature and skeletal maturation of two cohorts of Australian children and young adults over the past two decades. Skeletal maturation is based on the activation and interaction of a complex series of physiological mechanisms. However, the bone age was significantly different from each other ( p =0001). Greulich WW. (2014) 23:2734. Therefore, newer methods, such as artificial intelligence, might be used with the aim to guide endocrinologists and radiologists in the daily routine approach. During growth, biological maturity is defined by several parameters, including the characterization of skeletal maturity, sexual maturity, dental elements eruption, menarche, spermarche, deepening of the voice, growth spurt, and the achievement of 95% of the adult height (13). There are also exceptions with people who have a delayed bone age (bone age is younger than chronological age) due to being a late bloomer (someone starting puberty and hitting PHV later than average), being a late bloomer with delayed puberty, or having another condition. Roche AF CW, Thissen D. Growth Maturation and Body Composition: The Fels Longitudinal Study 1929-1991. 22. J Pediatr. (2011) 13:12033. The other primary skeletal component of height is the spine and skull. When the bone age reaches 16 years in females and 18 years in males, growth in height is over, and they have reached their full adult height. The bone age will determine the maturity of your child's bones, compared to your child's chronological (actual or "birthday") age. CG has written sections of the manuscript. A table of possible causes of abnormal stature and the expected bone age associated with each condition is provided below. doi: 10.1016/j.forsciint.2011.09.022, 101. Short stature is defined as a height more than two standard deviations below the mean for age (less than the 3rd percentile). (2013) 54:10249. (1989) 1:493494. Children with normal variants of height tend to have a normal growth velocity (5 cm [2 in] per year for children between five years of age and puberty) after catch-up or catch-down growth. Hochberg Z. Endocrine Control of SkeletalMaturation. In the last 20 years, newer methods have also been studied with the principal aim to mainly eliminate the variability related to interpretation according to the different methods. It's usually done by taking a single X-ray of the left wrist, hand, and fingers. (2001). Gupta N, Lustig RH, Kohn MA, Vittinghoff E. Determination of bone age in pediatric patients with Crohn's disease should become part of routine care. Gilsanz V, Kovanlikaya A, Costin G, Roe TF, Sayre J, Kaufman F. Differential effect of gender on the sizes of the bones in the axial and appendicular skeletons. To note, a proper assessment of bone age must always take into account differences between ethnic groups, sex, and any present pathological conditions. Growth at Adolescence. [Paternal height (cm) 13 cm + maternal height (cm)] 2, [Paternal height (in) 5 in + maternal height (in)] 2, [Paternal height (cm) + 13 cm + maternal height (cm)] 2, [Paternal height (in) + 5 in + maternal height (in)] 2, Constitutional delay of growth and puberty, Normal growth velocity, history of delayed puberty in parents, History and physical examination, bone age, Short parents, projected height consistent with midparental height, normal growth velocity, Midparental height, growth velocity, bone age; consider targeted laboratory evaluation, Height < 2 standard deviations below the mean for age with no identified pathology, normal growth velocity and bone age, Abdominal pain, malabsorption, anemia; short stature may be the only symptom, Tissue transglutaminase and total immunoglobulin A measurements; consider referral for endoscopy and biopsy, History of renal disease, poor weight gain, Abdominal pain, bloody stool, poor weight gain, Erythrocyte sedimentation rate and C-reactive protein measurements, referral for endoscopy and biopsy, Short limbs; long, narrow trunk; large head with prominent forehead, History of head trauma or cranial irradiation, central nervous system infection, IGF-1 and IGFBP-3 measurements, referral for growth hormone stimulation, other pituitary function tests, Hypoglycemia, birth length may be normal, height and bone age progressively delayed; jaundice, microphallus, midline craniofacial abnormalities, IGF-1 and IGFBP-3 measurements; referral for growth hormone stimulation, magnetic resonance imaging, other pituitary function tests, Mental retardation if not identified early, Newborn screening, thyroid-stimulating hormone and free thyroxine (T4) measurements, Born small for gestational age, normal height not achieved by 2 to 4 years of age, Focused laboratory testing to evaluate organic causes, consider referral to pediatric endocrinologist, History of poor nutrition, weight loss precedes height loss, Short stature, webbed neck, characteristic facies, short metacarpals, broad chest with widely spaced nipples, hyperconvex fingernails and toenails; may be normal appearing; decreased growth velocity and delayed puberty, Follicle-stimulating hormone, karyotyping, Erythrocyte sedimentation rate, C-reactive protein, Thyroid-stimulating hormone, free thyroxine (T4), Tissue transglutaminase and total immunoglobulin A, Serum luteinizing hormone, follicle-stimulating hormone, testosterone, Children with intrauterine growth retardation who do not catch up to the growth curve by 2 years of age, Height more than 3 standard deviations below the mean for age, No onset of puberty by 14 years of age for boys or 13 years of age for girls, Projected height more than 2 standard deviations (10 cm [4 in]) below the midparental height, Bone age more than 2 standard deviations below chronologic age, Diagnosis of conditions approved for recombinant growth hormone therapy, Family history of early puberty, bone age greater than chronologic age, Projected height within 5 cm (2 in) of midparental height, bone age greater than chronologic age, normal growth velocity after catch-up growth, Rapid childhood growth, goiter, tachycardia, hypertension, diarrhea, fine tremor, exophthalmos, Thyroid-stimulating hormone and free thyroxine (T4) measurements, Body mass index greater than the 95th percentile, slightly early onset of puberty, modest overgrowth/tall stature, minimally advanced bone age, Pituitary gigantism (excess growth hormone), Coarse facial features, mandibular prominence, broad root of nose, broad hands and feet, excessive sweating, hypertension, glucose intolerance, Measurement of insulinlike growth factor 1 and insulinlike growth factor binding protein 3, brain/pituitary magnetic resonance imaging, glucose suppression test, Girls: breast development before 8 years of age, Measurements of luteinizing hormone, follicle-stimulating hormone, estradiol, and testosterone, Boys: testicular enlargement (> 3 mL) before 9 years of age, Measurement of 17-hydroxyprogesterone, human chorionic gonadotropin, dehydroepiandrosterone, estradiol, and testosterone; bone age, Macrocephaly, macroglossia, ear pits, renal abnormality, omphalocele, umbilical hernia, hepatosplenomegaly, Insulin and glucose measurements, advanced bone age, karyotyping, renal ultrasonography, echocardiography, Marfan-like habitus, developmental delay, inferior subluxation of lens, Homocysteine and methionine measurements, dilated eye examination, Delayed puberty; infertility; small, firm testes; gynecomastia; high-pitched voice; learning disability, Measurements of luteinizing hormone, follicle-stimulating hormone, and testosterone; karyotyping, Increased arm span, thin extremities, superior subluxation of lens, hypotonia, kyphoscoliosis, cardiac valvular deformities, aortic root dilation, Clinical diagnosis using Ghent criteria, testing for, Large, protruding ears; long face; high-arched palate; hyperextensible fingers; pes planus; soft skin; macro-orchidism, Clinical suspicion based on dysmorphic features, testing for, Large head; long, thin face; broad forehead; prominent, narrow jaw; downward slanting palpebral fissures; feeding difficulties from birth; facial flushing; hypotonia, Clinical suspicion based on dysmorphic features, renal ultrasonography, echocardiography, advanced bone age, Small chin, broad forehead, hypertelorism, long philtrum, camptodactyly, Clinical suspicion based on dysmorphic features, renal ultrasonography, brain magnetic resonance imaging, advanced bone age (from birth).
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