Genetic testing of children with familial tall stature: is it worth doing?

CONTEXT: Familial tall stature (FTS) is considered to be a benign variant of growth with a presumed polygenic etiology. However, monogenic disorders with possible associated pathological features could also be hidden under the FTS phenotype. OBJECTIVES: To elucidate the genetic etiology in families with FTS and to describe their phenotype in detail. DESIGN, SETTINGS AND PATIENTS: Children with FTS (height in both the child and his/her taller parent >2 SD) referred to the Endocrinology center of Motol University Hospital were enrolled to the study. Their DNA was examined cytogenetically and via next-generation sequencing panel of 786 genes associated with growth. The genetic results were evaluated by the American College of Molecular Genetics and Genomics guidelines. All of the participants underwent standard endocrinological examination followed by specialized anthropometric evaluation. RESULTS: In total, 34 children (19 girls) with FTS were enrolled in the study. Their median height and their taller parent's height were 3.1 SD and 2.5 SD, respectively. The genetic cause of FTS was elucidated in 11/34 (32.4%) children (47, XXX and 47, XYY karyotypes, SHOX duplication, and causative variants in NSD1 [in 2], SUZ12 [in 2], FGFR3, CHD8, GPC3, and PPP2R5D genes). Ten children had absent syndromic sings and 24 had dysmorphic features. CONCLUSION: Monogenic (and cytogenetic) etiology of FTS can be found among children with FTS. Genetic examination should be considered in all children with FTS regardless of the presence of dysmorphic features.

Tall stature and gigantism in adult patients with acromegaly.

OBJECTIVES: Increased height in patients with acromegaly could be a manifestation of growth hormone (GH) excess before epiphysis closure. The aim of this study was to evaluate the relationship between the height of adult patients with GH excess related to mid-parental height (MPH) and population mean and to find whether taller patients with acromegaly come from tall families. METHODS: This is a single-centre, observational study involving 135 consecutive patients with acromegaly diagnosed as adults and no family history of GH excess. We established three categories for height for patients with acromegaly: normal stature, tall stature (TS, height above the 97th percentile (1.88 standard deviations (SD)) to <3 SD for gender- and country-specific data or as a height which was greater than 1.5 SD but less than 2 SD above the MPH) and gigantism (height which was greater than 3 SD) above the gender- and country-specific mean or greater than 2 SD above MPH). RESULTS: Thirteen percent (17/135) of patients (53% females) met the criteria for gigantism, 10% (14/135) fulfilled the criteria for TS (57% females). Parents and adult siblings were not taller than the population mean. CONCLUSION: In a group of 135 consecutive adult patients with acromegaly, 23% had increased height based on country-specific and MPH data: 13% presented with gigantism while 10% had TS. The frequency of gigantism and TS in patients diagnosed with GH excess as adults is not higher in males than in females. Patients with acromegaly come from normal-stature families.

Epigenetic Causes of Overgrowth Syndromes.

Human overgrowth disorders are characterized by excessive prenatal and/or postnatal growth of various tissues. These disorders often present with tall stature, macrocephaly, and/or abdominal organomegaly and are sometimes associated with additional phenotypic abnormalities such as intellectual disability and increased cancer risk. As the genetic etiology of these disorders have been elucidated, a surprising pattern has emerged. Multiple monogenic overgrowth syndromes result from variants in epigenetic regulators: variants in histone methyltransferases NSD1 and EZH2 cause Sotos syndrome and Weaver syndrome, respectively, variants in DNA methyltransferase DNMT3A cause Tatton-Brown-Rahman syndrome, and variants in chromatin remodeler CHD8 cause an autism spectrum disorder with overgrowth. In addition, very recently, a variant in histone reader protein SPIN4 was identified in a new X-linked overgrowth disorder. In this review, we discuss the genetics of these overgrowth disorders and explore possible common underlying mechanisms by which epigenetic pathways regulate human body size.

Tall stature and gigantism in transition age: clinical and genetic aspects-a literature review and recommendations.

PURPOSE: Tall stature is defined as height greater than the threshold of more than 2 standard deviations above the average population height for age, sex, and ethnicity. Many studies have described the main aspects of this condition during puberty, but an analysis of the characteristics that the physician should consider in the differential diagnosis of gigantism-tall stature secondary to a pituitary tumour-during the transition age (15-25 years) is still lacking. METHODS: A comprehensive search of English-language original articles was conducted in the MEDLINE database (December 2021-March 2022). We selected all studies regarding epidemiology, genetic aspects, and the diagnosis of tall stature and gigantism during the transition age. RESULTS: Generally, referrals for tall stature are not as frequent as expected because most cases are familial and are usually unreported by parents and patients to endocrinologists. For this reason, lacking such experience of tall stature, familiarity with many rarer overgrowth syndromes is essential. In the transition age, it is important but challenging to distinguish adolescents with high constitutional stature from those with gigantism. Pituitary gigantism is a rare disease in the transition age, but its systemic complications are very relevant for future health. Endocrine evaluation is crucial for identifying conditions that require hormonal treatment so that they can be treated early to improve the quality of life and prevent comorbidities of individual patient in this age range. CONCLUSION: The aim of our review is to provide a practical clinical approach to recognise adolescents, potentially affected by gigantism, as early as possible.

Exome Sequencing Identifies Multiple Genetic Diagnoses in Children with Syndromic Growth Disorders.

OBJECTIVE: To evaluate the presence of multiple genetic diagnoses in syndromic growth disorders. STUDY DESIGN: We carried out a cross-sectional study to evaluate 115 patients with syndromic tall (n = 24) or short stature (n = 91) of unknown cause from a tertiary referral center for growth disorders. Exome sequencing was performed to assess germline single nucleotide, InDel, and copy number variants. All variants were classified according to ACMG/AMP guidelines. The main outcome measured was the frequency of multiple genetic diagnoses in a cohort of children with syndromic growth disorders. RESULTS: The total diagnostic yield of the cohort was 54.8% (63/115). Six patients had multiple genetic diagnoses (tall stature group = 2; short stature group = 4). The proportion of multiple diagnoses within total cases was 5.2% (6/115), and within solved cases was 9.5% (6/63). No characteristics were significantly more frequent when compared with patients with single or multiple genetic findings. Among patients with multiple diagnoses, 3 had syndromes with overlapping clinical features, and the others had syndromes with distinct phenotypes. CONCLUSION: Recognition of multiple genetic diagnoses as a possibility in complex cases of syndromic growth disorders opens a new perspective on treatment and genetic counseling for affected patients, defying the medical common sense of trying to fit all findings into one diagnosis.

Identification of novel genes including NAV2 associated with isolated tall stature.

Very tall people attract much attention and represent a clinically and genetically heterogenous group of individuals. Identifying the genetic etiology can provide important insights into the molecular mechanisms regulating linear growth. We studied a three-generation pedigree with five isolated (non-syndromic) tall members and one individual with normal stature by whole exome sequencing; the tallest man had a height of 211 cm. Six heterozygous gene variants predicted as damaging were shared among the four genetically related tall individuals and not present in a family member with normal height. To gain insight into the putative role of these candidate genes in bone growth, we assessed the transcriptome of murine growth plate by microarray and RNA Seq. Two (Ift140, Nav2) of the six genes were well-expressed in the growth plate. Nav2 (p-value 1.91E-62) as well as Ift140 (p-value of 2.98E-06) showed significant downregulation of gene expression between the proliferative and hypertrophic zone, suggesting that these genes may be involved in the regulation of chondrocyte proliferation and/or hypertrophic differentiation. IFT140, NAV2 and SCAF11 have also significantly associated with height in GWAS studies. Pathway and network analysis indicated functional connections between IFT140, NAV2 and SCAF11 and previously associated (tall) stature genes. Knockout of the all-trans retinoic acid responsive gene, neuron navigator 2 NAV2, in Xenopus supports its functional role as a growth promotor. Collectively, our data expand the spectrum of genes with a putative role in tall stature phenotypes and, among other genes, highlight NAV2 as an interesting gene to this phenotype.

Analysis of the distribution of adult height standard deviation scores in relation to prepubertal height standard deviation scores using longitudinal growth data: -Investigation of the catch-up rates of children with short stature to attain normal adult height.

Using the longitudinal growth data of 13,809 individuals in the Akita Prefecture, the percentage distributions of their adult height (AH) standard deviation scores (SDS) in relation to their prepubertal height SDS were obtained. The AH SDS increased with negative prepubertal height SDS and decreased with positive prepubertal height SDS, showing that a greater amount of change was associated with a greater interval of the prepubertal height SDS from the mean. The proportions of individuals who achieved normal AH stratified by prepubertal height SDS were as follows: 67.1%, in the group with prepubertal height SDS of -2.5 < to ≤ -2.0 SD, 46.0% in the group with -3.0 < to ≤ -2.5 SD, 75.2% in the group with +2.0 ≤ to < +2.5 SD, and 55.1% in the group with +2.5 ≤ to < +3.0 SD. Of all participants with short stature at prepuberty, 58.4%, 33.8%, 8.3%, and 0% of those with prepubertal height SDS of ≤ -2.0 SD, ≤ -2.5 SD, ≤ -3.0 SD, and ≤ -3.5 SD attained normal AH, respectively. On average, it is difficult for children with prepubertal height SDS of ≤ -2.5 SD to attain normal AH.

TGF-ß and BMP Signaling Pathways in Skeletal Dysplasia with Short and Tall Stature.

The transforming growth factor ß (TGF-ß) and bone morphogenetic protein (BMP) signaling pathways play a pivotal role in bone development and skeletal health. More than 30 different types of skeletal dysplasia are now known to be caused by pathogenic variants in genes that belong to the TGF-ß superfamily and/or regulate TGF-ß/BMP bioavailability. This review describes the latest advances in skeletal dysplasia that is due to impaired TGF-ß/BMP signaling and results in short stature (acromelic dysplasia and cardiospondylocarpofacial syndrome) or tall stature (Marfan syndrome). We thoroughly describe the clinical features of the patients, the underlying genetic findings, and the pathomolecular mechanisms leading to disease, which have been investigated mainly using patient-derived skin fibroblasts and mouse models. Although no pharmacological treatment is yet available for skeletal dysplasia due to impaired TGF-ß/BMP signaling, in recent years advances in the use of drugs targeting TGF-ß have been made, and we also discuss these advances.

Novel duplication of the cell adhesion molecule L1-like gene in an individual with cognitive impairment, tall stature, and obesity: A case report.

The gene that codes for the close homolog of L1 (CHL1 gene) is located in the 3p26.3 cytogenetic band in the distal portion of the 3p chromosome. This gene is highly expressed in the central nervous system and plays an important role in brain formation and plasticity. Complete or partial CHL 1 gene-deficient mice have demonstrated neurocognitive deficits. In humans, mutations of the CHL 1 gene are infrequent with most mutations described in the literature as deletions. This case report describes an individual with a duplication in the CHL 1 and a presentation consistent with a syndromic form of neurocognitive impairment. To the best of our knowledge, this mutation has not been previously described in the literature.

Clinical and genetic features of luscan-lumish syndrome associated with a novel de novo variant of SETD2 gene: Case report and literature review.

Introduction: Luscan-Lumish syndrome (LLS) is currently recognized as a rarely-observed condition featured with overgrowth, macrocephaly, obesity, type I Chiari malformation, and linguistic retardation. So far, there have been only a few LLS cases registered worldwide, but with none of them reported from China. To acquire a deeper understanding on the clinical and genetic features of this disease, a Chinese boy with LLS caused by a heterozygous variant in SETD2 gene was investigated in the present study. Methods: The patient was clinically examined and the medical history of his family was collected. Genetic testing was performed to determine the genetic etiology. Results: The proband was a boy aged 5-year-7-month-old, who was referred to our hospital due to "being a slow learner in kindergarten". The child had a history of delayed motor and language development in comparison to his peers. After admission, physical examination revealed tall stature and macrocephaly as the major manifestation, in addition to a relatively lower rating in intelligence assessment as well as abnormal MRI images showing a slightly shorter corpus callosum accompanied by a mildly thinner corpus callosum body. Whole exome sequencing (WES) revealed a heterozygous c.2514_2516delTAG (p.Ser838del) variant in SETD2 gene, which was subsequently identified as a novel de novo variant. According to the standardized genetic variant classification published by the American College of Medical Genetics and Genomics (ACMG), the variant, with a pathogenicity analysis result indicating PS2 + PM2_Supporting + PM4, was determined to be likely pathogenic. Through literature review, the clinical phenotypes of the 15 LLS cases were summarized, including 8 cases of overgrowth (53%), 13 cases of macrocephaly (87%), 11 cases of developmental delay (73%), 8 cases of autism (53%), and 7 cases of special facial features (47%). Besides, abnormal craniocerebral MRI findings were noticed in 7 cases. Despite that the mutation sites of the 15 patients varied from case to case, they showed a uniformly distributed pattern throughout the whole SETD2 gene, including 5 missense mutations, 5 frameshift mutations and 5 non-sense mutations. Conclusion: LLS, not having been recognized till recent years, is identified as an autosomal dominant syndrome triggered by SETD2 gene mutation. As the first report of LLS in China, the case in our study was proved to be associated with a unique type of SETD2 gene mutation that has never been reported previously, which is believed to enrich the mutation spectrum of SETD2 gene and also, deepening the clinicians' understanding on the disease.

Comparison of Commonly Used Methods to Predict the Final Height in Constitutional Tall Stature

Objective: To determine the accuracy of adult height prediction in children with constitutional tall stature. Methods: The medical records of 138 non-syndromatic prepubertal and early pubertal children (52 male, 86 female) with a height of ≥90th percentile born between the years 1975 and 1988 were included in this study. Using the Bayley-Pinneau (BP) and Tanner-Whitehouse I (TWI) prediction methods, their height standard deviation score (SDS) at referral was compared with their height SDS at age 17 years when measured at the IDF conscription center. Results: While remaining tall, the height SDS at age 17 years was lower than that at referral decreasing from 2.13±1 to 1.65±1.21 in boys and from 2.48±1 to 2.15±1 in girls. Conclusion: The prediction by the BP and TWI methods can be useful for estimating adult height in constitutional tall stature even in the prepubertal and early pubertal period. However, the fallibility of these methods should be kept in mind during clinical practice. We think that this study will shed light on these issues.

Aromatase deficiency in a tall man: Case report of two novel mutations and review of literature.

Aromatase (CYP19A1) is the only enzyme known to catalyse the conversion of androgen to estrogen. Aromatase deficiency occurs due to mutation in CYP19A1gene which has an autosomal recessive inheritance pattern. It leads to decrease in estrogen synthesis and delayed epiphyseal closure, eunuchoid habitus and osteopenia. We are presenting here, a 24 years old male, with history of progressive increase in height and knock knees. X-ray showed open wrist and knee epiphysis. The serum testosterone level was normal and serum estradiol level was undetectable. Semen analysis showed azoospermia. Clinical exome sequencing gave two novel mutations in CYP19A1. The first variant was a novel single nucleotide deletion of thiamine at 570th base of the cDNA (c.570delT) of CYP19A1 gene. The second variant detected was again a novel one in the same gene in Exon 5 corresponding 344th base of the cDNA (c344G>A) resulting in a missense mutation of 115th arginine to glutamine in the protein. Sanger sequencing showed that the later mutation was inherited from the father. The patient was started on oral estradiol valerate for epiphyseal closure to prevent further increase in height. Only 15 mutations have been reported in the aromatase gene in males till date, our report of these novel mutations will be an add-on to the literature.

Genetic diagnosis for adult patients at a genetic clinic.

Clinical utility of genetic testing has rapidly increased in the past decade to identify the definitive diagnosis, etiology, and specific management. The majority of patients receiving testing are children. There are several barriers for genetic tests in adult patients; barriers may arise from either patients or clinicians. Our study aims to realize the detection rate and the benefits of genetic tests in adults. We conducted a prospective study of 10 adult patients who were referred to a genetic clinic. Exome sequencing (ES) was pursued in all cases, and chromosomal microarray (CMA) was performed for six cases. Our result is impressive; six cases (60%) received likely pathogenic and pathogenic variants. Four definitive diagnosis cases had known pathogenic variants in KCNJ2, TGFBR1, SCN1A, and FBN1, whereas another two cases revealed novel likely pathogenic and pathogenic variants in GNB1 and DNAH9. Our study demonstrates the success in genetic diagnosis in adult patients: four cases with definitive, two cases with possible, and one case with partial diagnosis. The advantage of diagnosis is beyond obtaining the diagnosis itself, but also relieving any doubt for the patient regarding any previous questionable diagnosis, guide for management, and recurrence risk in their children or family members. Therefore, this supports the value of genetic testing in adult patients.

Preliminary results of two novel devices for epiphysiodesis in the reduction of excessive predicted final height in tall stature.

BACKGROUND: In the treatment of tall stature, the reduction of excessive predicted final height can either be achieved by hormonal treatment or surgically by temporary (tED) or permanent (pED) epiphysiodesis. The present study evaluates the preliminary results of two novel devices for tED and pED around the knee to reduce the predicted final height. MATERIALS AND METHODS: A retrospective analysis was performed to evaluate the clinical and radiographic outcome after bilateral epiphysiodesis for the treatment of tall stature. A cohort of 34 patients (16 girls, 18 boys) who underwent either tED or pED between 2015 and 2020 were eligible for analysis based on the electronic patient records and picture archiving and communication system of our orthopaedic teaching hospital. tED was conducted in 11 patients (32%) through bilateral implantation of four RigidTacks™ (Merete, Berlin, Germany) around the knee. Twenty-three patients (68%) received pED, performed with an EpiStop™ trephine (Eberle, Wurmberg, Germany). The mean overall follow-up time was 2.9 years. RESULTS: The mean age at surgery was 12.3 years in girls and 13.2 years in boys. Patients had a mean body height of 175.2 cm in girls and 184.7 cm in boys at surgery. The mean predicted final height was 191.4 cm in girls and 210.4 cm in boys. At the last follow-up, 26 patients (76.5%) had achieved skeletal maturity. The mean height of skeletally mature patients was 187.2 cm in girls and 198.5 cm in boys. A mean reduction of the predicted final height of 5.9 cm in girls and 8.7 cm in boys was achieved, corresponding to a reduction in remaining growth of 46% in girls and 38% in boys. Secondary frontal plane deformities of the knee were detected in 5/11 patients (45.5%) in the tED group and 1/23 treatments (4.3%) in the pED group. CONCLUSIONS: tED and pED have both proven to be efficient at achieving growth inhibition to reduce excessive predicted height. However, tED has been associated with an increased risk of secondary angular deformities of the knee. Furthermore, the risk of implant-related complications and the necessity of a subsequent surgical intervention for implant removal have led our study group to abandon tED when treating tall stature. Long-term results of both procedures are pending.

Postoperative growth rate affects time to growth arrest after percutaneous physiodesis: A radiostereometric analysis.

Purpose: The aim of this study was to determine the time at which physeal arrest is achieved after percutaneous physiodesis, and whether immediate postoperative growth rate affects the time to reach physeal arrest. Methods: Radiostereometric analysis, with implantation of tantalum balls as radiographic markers on each side of the physes, was used to measure residual longitudinal growth in 21 children (10 boys and 11 girls) after percutaneous physiodesis for leg length discrepancy or extreme tall stature. In total, 25 femoral and 20 tibial physes were operated on. Median age at surgery was 13.9 years (range = 11.4-16.1). Radiostereometric analysis was performed postoperatively and after 3, 6, 9, 12, 26, and 52 weeks. Longitudinal growth rate <50 µm per week was defined as physeal arrest. Descriptive statistics were used for evaluation. Results: Physeal arrest was obtained in 19 of the 21 children (40 physes) within 12 weeks postoperatively. One child was reoperated on in three out of four physes because of continued growth, and in one child, delayed physeal arrest was present at 26 weeks postoperatively. Time to physeal arrest was longer in physes with a higher immediate postoperative growth rate. Conclusion: Postoperative follow-up with radiostereometric analysis at 12 and 15 weeks can determine whether physeal arrest has been achieved. The immediate postoperative growth rate after physiodesis seems to affect the time to physeal arrest. This implies that the risk for complications is greater for children during an accelerated growth period, for example, in boys, younger children and in distal femoral physes. Level of evidence: level III.

Broadening the Spectrum of Loss-of-Function Variants in NPR-C-Related Extreme Tall Stature.

CONTEXT: Natriuretic peptide receptor-C (NPR-C, encoded by NPR3) belongs to a family of cell membrane-integral proteins implicated in various physiological processes, including longitudinal bone growth. NPR-C acts as a clearance receptor of natriuretic peptides, including C-type natriuretic peptide (CNP), that stimulate the cGMP-forming guanylyl cyclase-coupled receptors NPR-A and NPR-B. Pathogenic variants in CNP, NPR2, and NPR3 may cause a tall stature phenotype associated with macrodactyly of the halluces and epiphyseal dysplasia. OBJECTIVE: Here we report on a boy with 2 novel biallelic inactivating variants of NPR3. METHODS: History and clinical characteristics were collected. Biochemical indices of natriuretic peptide clearance and in vitro cellular localization of NPR-C were studied to investigate causality of the identified variants. RESULTS: We identified 2 novel compound heterozygous NPR3 variants c.943G>A p.(Ala315Thr) and c.1294A>T p.(Ile432Phe) in a boy with tall stature and macrodactyly of the halluces. In silico analysis indicated decreased stability of NPR-C, presumably resulting in increased degradation or trafficking defects. Compared to other patients with NPR-C loss-of-function, the phenotype seemed to be milder: pseudo-epiphyses in hands and feet were absent, biochemical features were less severe, and there was some co-localization of p.(Ile432Phe) NPR-C with the cell membrane, as opposed to complete cytoplasmic retention. CONCLUSION: With this report on a boy with tall stature and macrodactyly of the halluces we further broaden the genotypic and phenotypic spectrum of NPR-C-related tall stature.

Presentation of Congenital Portosystemic Shunts in Children.

BACKGROUND: Congenital portosystemic shunts (CPSS) are rare vascular anomalies resulting in communications between the portal venous system and the systemic venous circulation, affecting an estimated 30,000 to 50,000 live births. CPSS can present at any age as a multi-system disease of variable severity mimicking both common and rare pediatric conditions. CASE PRESENTATIONS: Case A: A vascular malformation was identified in the liver of a 10-year-old girl with tall stature, advanced somatic maturation, insulin resistance with hyperinsulinemia, hyperandrogenemia and transient hematuria. Work-up also suggested elevated pulmonary pressures. Case B: A young girl with trisomy 8 mosaicism with a history of neonatal hypoglycemia, transient neonatal cholestasis and tall stature presented newly increased aminotransferase levels at 6 years of age. Case C: A 3-year-old boy with speech delay, tall stature and abdominal pain underwent abdominal ultrasound (US) showing multiple liver nodules, diagnosed as liver hemangiomas by hepatic magnetic resonance imaging (MRI). Management and outcome: After identification of a venous malformation on liver Doppler US, all three patients were referred to a specialized liver center for further work-up within 12 to 18 months from diagnosis. Angio-computed tomography (CT) scan confirmed the presence of either an intrahepatic or extrahepatic CPSS with multiples liver nodules. All three had a hyperintense signal in the globus pallidus on T1 weighted cerebral MRI. Right heart catheterization confirmed pulmonary hypertension in cases A and C. Shunts were closed either using an endovascular or surgical approach. Liver nodules were either surgically removed if there was a risk of malignant degeneration or closely monitored by serial imaging when benign. CONCLUSION: These cases illustrate most of the common chief complaints and manifestations of CPSS. Liver Doppler US is the key to diagnosis. Considering portosystemic shunts in the diagnostic work-up of a patient with unexplained endocrine, liver, gastro-intestinal, cardiovascular, hematological, renal or neurocognitive disorder is important as prompt referral to a specialized center may significantly impact patient outcome.

Approach to the Patient With Pseudoacromegaly.

Pseudoacromegaly encompasses a heterogeneous group of conditions in which patients have clinical features of acromegaly or gigantism, but no excess of GH or IGF-1. Acromegaloid physical features or accelerated growth in a patient may prompt referral to endocrinologists. Because pseudoacromegaly conditions are rare and heterogeneous, often with overlapping clinical features, the underlying diagnosis may be challenging to establish. As many of these have a genetic origin, such as pachydermoperiostosis, Sotos syndrome, Weaver syndrome, or Cantú syndrome, collaboration is key with clinical geneticists in the diagnosis of these patients. Although rare, awareness of these uncommon conditions and their characteristic features will help their timely recognition.

Fetal weight estimation in tall women: is ultrasound more accurate than clinical assessment? A prospective trial.

PURPOSE: Estimated fetal weight (EFW) is crucial for clinical decision-making during pregnancy and labor. Maternal habitus impacts its accuracy. This study compared the accuracy of clinical versus ultrasound EFW in tall pregnant women (height ≥ 172 cm, 90th percentile). METHODS: In this prospective study, tall pregnant women at term, who arrived for a prenatal visit and delivered within a week, underwent clinical and ultrasound assessments of estimated fetal weight. Each woman served as her own control. After delivery, birth weight was compared to the clinical and ultrasound EFW. The primary outcome was the accuracy of each method in predicting the actual birth weight. RESULTS: All 100 women included in this trial underwent clinical and ultrasound estimations of fetal weight. Mean maternal height was 175.7 ± 3.3 (172-185) cm. More clinical EFW swere inaccurate compared to ultrasound (25 (25%) vs. 6 (6%), respectively, p < 0.001). Both clinical (3583 g) and ultrasound (3490 g) evaluations underestimated the fetal weights compared to the birth weights (3664 g, p < 0.001). In the macrosomic fetal group, both the clinical (3983 g) and ultrasound (3767 g) estimates were significantly inaccurate compared to the birth weights (4237 g, p < 0.001). CONCLUSION: Among tall women, ultrasound EFW is more accurate than clinical EFW. TRIAL REGISTRATION NUMBER AND DATE OF REGISTRATION: IRB-0016-17-MMC, Clinical-Trials.gov identifier NCT03206281.