Alternating Hemiplegia of Childhood: neurological comorbidities and intrafamilial variability.

BACKGROUND: Alternating of Childhood (AHC) is an uncommon and complex disorder characterized by age of onset before 18 months with recurrent hemiplegia of one or either sides of the body or quadriplegia. The disorder is mainly caused by mutations in ATP1A3 gene, and to a lesser extent in ATP1A2 gene. In AHC neurological co-morbidities are various and frequently reported including developmental delay, epilepsy, tonic or dystonic spells, nystagmus,autonomic manifestations with intrafamilial variability. CASE PRESENTATION: Clinical and genetic findings of a couple of twins (Family 1: Case 1 and Case 2) and a couple of siblings (Family 2: Case 3 and Case 4) coming from two different Italian families affected by AHC were deeply examined. In twins of Family 1, a pathogenic variant in ATP1A3 gene (c.2318A>G) was detected. In siblings of Family 2, the younger brother showed a novel GRIN2A variant (c.3175 T > A), while the older carried the same GRIN2A variant, and two missense mutations in SCNIB (c.632 > A) and KCNQ2 (1870 G > A) genes. Clinical manifestations of the four affected children were reported along with cases of AHC drawn from the literature. CONCLUSIONS: Hemiplegic episode is only a sign even if the most remarkable of several and various neurological comorbidities in AHC affected individuals. Molecular analysis of the families here reported showed that clinical features of AHC may be also the result of an unexpected genetic heterogeneity.

Development and validation of the Pediatric-Youth Hyperphagia Assessment for Prader-Willi syndrome.

OBJECTIVES: Hyperphagia is a highly stressful, life-threatening feature of Prader-Willi syndrome (PWS). It is important to assess this complex behavior accurately over time. This study aimed to develop and validate the Pediatric-Youth Hyperphagia Assessment for Prader-Willi syndrome (PYHAP) as a tool targeting children and adolescents. METHODS: After an extensive literature review and qualitative interviews, the final version of the PYHAP with 14 questions in 3 domains (verbal [5], behavior [4], and social [5]) was developed and tested at Samsung Medical Center in Seoul, Korea from July 2018 to September 2019. Exploratory factor analysis and confirmatory factor analysis (CFA) were performed to confirm construct validity. The correlations between the PYHAP and the Korean Children's Eating Behavior Questionnaire (K-CEBQ) were calculated to evaluate convergent and discriminant validity. Criterion validity and the validity of the response categories were also tested. RESULTS: Cronbach's alpha coefficient of the PYHAP was 0.91. The fit indices for CFA were good (comparative fit index, 0.87; standardized root mean squared residual, 0.08). The domains of the PYHAP were closely correlated with the relevant domains of the K-CEBQ. The accuracy of the PYHAP score for predicting uncontrolled hyperphagia was good (area under the curve, 0.75; 95% confidence interval, 0.65 to 0.85). CONCLUSIONS: The PYHAP was confirmed to be a reliable and valid tool to evaluate hyperphagia in children and adolescents with PWS via caregivers' assessments. It is recommended to use the PYHAP to communicate with parents or caregivers about patients' hyperphagia or to monitor and manage extreme behaviors in children with PWS.

Appropriate Age for Height Control Treatment in Patients With Marfan Syndrome.

Objective: This study aimed to determine the most appropriate age for height control treatment in patients with Marfan syndrome (MFS). Materials and Methods: This retrospective study included patients with MFS who underwent height control treatment with estradiol valerate. The estrogen dose was increased according to the height change. The cut-off age for the maximum difference between the expected height and actual final height was evaluated. Results: Seventeen patients were included in this study. The difference between the height predicted by the growth curve and the final height (gcHtD) and that predicted by the bone age and the final height (baHtD) was the largest in the 10.5 years age group (p=0.0045 and p=0.0237, respectively). The gcHtD was 10.6 (10.2, 13.5) cm for patients aged ≤10.5 years, whereas it was 0.6 (-3.65, 5.85) cm for patients aged >10.5 years. The baHtD was 10.1 (7.31, 11.42) cm for patients aged ≤10.5 years, while it was 3.83 (0.84, 6.4) cm for patients aged >10.5 years. When height change was observed for a minimum of 6 months after completion of estrogen treatment, the average growth was 0.6 (0.2, 2.1) cm. Conclusion: Initiating height control treatment before the age of 10.5 years is effective in female patients with MFS.

Clinical characteristics, treatment outcomes, and occurrence of diabetes mellitus after pancreatic resection of solid pseudopapillary tumor in children and adolescents: A single institution experience with 51 cases.

BACKGROUND: Solid pseudopapillary tumors (SPTs) are rare, but they comprise the majority of pediatric pancreatic neoplasms. However, studies on these conditions in pediatric patients are lacking. The aim of this study was to investigate the clinical characteristics and treatment outcomes in children and adolescents with SPTs. METHODS: This retrospective study included 51 patients with SPTs who had undergone pancreatic tumor resection before the age of 19 years at Samsung Medical Center in Korea (from November 1994 to August 2020). We investigated the postoperative outcomes. RESULTS: Of the 51 patients with SPTs (female, 88.2%), the median age at diagnosis was 14 years (range, 8-19). The most common symptom was abdominal pain (60.8%), and 14 patients (27.5%) were asymptomatic. The median maximal tumor diameter was 7 cm (range, 1.4-14), and the pancreatic body and/or tail were involved in 68.6% of patients. The short-term complication rate was 21.5%, and the recurrence rate was 5.9%. New-onset diabetes mellitus (NODM) occurred in four patients. CONCLUSIONS: The ideal treatment for SPTs is complete resection of the tumor; however, long-term postoperative complications including NODM should be monitored carefully, particularly in children and adolescents.

The First Korean Family with Aarskog-Scott Syndrome Harboring a Novel Mutation in FGD1 Diagnosed via Targeted Gene Panel Sequencing.

Aarskog-Scott syndrome (AAS), also known as faciogenital dysplasia (FGD, OMIM # 305400), is an X-linked recessive inheritance, characterized by short stature, facial dysmorphism, and skeletal abnormalities. We report the clinical and molecular analysis of a family with ASS. A 31-month-old boy and his cousin were initially mistaken for having Noonan syndrome owing to short stature and facial dysmorphism. Considering the family history, we suspected the possibility of an X-linked genetic disease and performed targeted gene panel sequencing; a novel hemizygous variant c.1192-1 G>A in FGD1 was identified in both the proband and his cousin. This is the first report of ASS in Korea. Targeted gene panel sequencing can be an effective tool for diagnosing rare complex syndromes, including ASS.

Clinical, Hormonal, and Neuroradiological Characteristics and Therapeutic Outcomes of Prolactinomas in Children and Adolescents at a Single Center.

Background/Purpose: A prolactinoma is the most common pituitary adenoma, but it is relatively rare in childhood and adolescence. There is only limited research about the clinical spectrum, treatment, and outcomes of prolactinomas in childhood and adolescence. In this single-center cohort study, we assessed the clinical, hormonal, and neuroradiological characteristics and therapeutic outcomes of children and adolescents with prolactinomas. Methods: This retrospective cohort study included 25 patients with prolactinomas diagnosed before 19 years of age, who presented at Samsung Medical Center during a 15-year period (March 2005 to August 2019). Results: The median age at diagnosis was 16.9 (range 10.1-18.5) years, and 80% of the patients were female. The common clinical manifestations at diagnosis were galactorrhea (10/20, 50%) and amenorrhea (9/20, 45%) among females and visual field defects (3/5, 60%) and headaches (2/5, 40%) among males. In our cohort, macroadenomas accounted for 56% of cases, and the rate of overall responsiveness to dopamine agonists (DAs) was 56% (10/18). Male gender, the prolactin (PRL) level at diagnosis, and the presence of panhypopituitarism were positively correlated with maximum tumor diameter (r = 0.443, P = 0.026; r = 0.710, P < 0.001; and r = 0.623, P = 0.001, respectively). After the trans-sphenoidal approach (TSA), 53% (8/15) of patients showed normalization of the PRL level. Three patients, who underwent gamma knife surgery (GKS) owing to either resistance or intolerance to DAs or recurrence after the TSA, achieved a normal PRL level accompanied with marked tumor reduction and symptom remission. Conclusions: A macroprolactinoma is more prevalent than a microprolactinoma in children and adolescents than in adults. Male gender, increased PRL levels, and the presence of panhypopituitarism at diagnosis are closely related to macroprolactinomas in children and adolescents.

Clinical Presentation and Treatment Outcomes of Children and Adolescents With Pheochromocytoma and Paraganglioma in a Single Center in Korea.

Purpose: Pheochromocytoma (PCC) and paraganglioma (PGL) (PPGL) are rare neuroendocrine tumors, and data on managing these conditions in children and adolescents are lacking. The objective of this study was to demonstrate the clinical presentation and treatment outcomes in children and adolescents with PPGL in a single tertiary care center in Korea. Methods: This retrospective study included 23 patients diagnosed with PCC (n = 14) and PGL (n = 9) before the age of 21 at Samsung Medical Center (from June 1994 to June 2019). We describe age, gender, family history, clinical characteristics, laboratory findings, pathologic findings, therapeutic approaches, and treatment outcomes. Results: Of the 23 patients, 14 had PCC and nine had PGL. The median age at diagnosis was 16.8 years (range, 6.8-20.8 years). The common presenting symptoms were hypertension (n = 10), headache (n = 9), palpitation (n = 4), and sweating (n = 4). The plasma or 24-hour urine catecholamine and/or metabolite concentrations were markedly elevated in 22 patients with PPGL, but were normal in one patient with carotid body PGL. All tumors were visualized on computed tomography. Genetic tests were performed in 15 patients, and seven patients showed mutations in RET (n = 3), SDHB (n = 3), and VHL (n = 1). All patients underwent surgery, and complete excision was performed successfully. Three patients with metastasis underwent postoperative adjuvant therapy. Conclusion: This study suggests that pediatric PPGL tends to be extra-adrenal and bilateral and shows a higher potential for genetic mutations. Considering the hereditary predisposition of pediatric PPGL, genetic screening tests are strongly recommended, and lifelong follow-up is needed to detect recurrence and metastasis. Further research with a larger sample size and routine genetic screening is needed to better understand the genetic conditions and long-term prognosis of PPGL.

Identification of a novel mutation in EXT2 in a fourth-generation Korean family with multiple osteochondromas and overview of mutation spectrum.

Multiple osteochondromas (MOs) or hereditary multiple exostoses is a rare autosomal-dominant disease characterized by growths of MOs, which are benign cartilage-capped bone tumors that grow away from the growth plates. Almost 90% of MOs have a molecular explanation and 10% are unexplained. MOs are genetically heterogeneous with two causal genes on 8q24.11 (EXT1) and 11p12 (EXT2), with a higher frequency in EXT1. MO is a very rare genetic disorder, and the genotype-phenotype of MO with EXT2 mutation has not been well investigated in Korea. We present the clinical radiographic and molecular analysis of a four-generation Korean family with 11 MO-affected members (seven males and four females). The affected members from the third generation available for molecular analysis and their detailed medical histories showed moderate-to-severe phenotypes (clinical classes II-III), including bony deformities and limb misalignment with pain requiring surgical correction. The x-rays showed MOs in multiple sites. A novel EXT2 frameshift mutation (c.590delC, p.P197Qfs*73) was revealed by targeted exome sequencing in the affected members of this family. In this article, we not only expand the phenotypic-genotypic spectrum of MOs but also highlight the phenotypic heterogeneity in a family with the same mutation. In addition, we compiled the mutation spectrum of EXT2 from a literature review and identified that exon 2 of EXT2 is a mutation hot spot. Early medical attention with diagnosis of MO through careful examination of the clinical manifestations and genetic analysis can provide the opportunity to establish coordinated multispecialty management of the patient.

Clinical Characteristics of Autosomal Dominant GJA1 Missense Mutation Linked to Oculodentodigital Dysplasia in a Korean Family.

PURPOSE: We aimed to present a comprehensive assessment of the ophthalmic characteristics of genetically confirmed oculodentodigital dysplasia (ODDD) in 4 members of a single Korean family across 3 generations. PATIENTS AND METHODS: The characteristics of 4 affected ODDD patients were evaluated. Comprehensive ophthalmic and medical examinations were performed in 3 patients including the proband, together with genetic analysis, and retrospective chart review was conducted for an affected ancestor. For genetic analysis, targeted gene panel sequencing was conducted using genomic DNA extracted from peripheral blood. RESULTS: All affected individuals in this family showed shared ophthalmic abnormalities of microcornea, microphthalmia, elevated intraocular pressure, and shallow anterior chamber, all of which have been reported as typical ocular features of ODDD. Myopic refractive error despite short axial length and thick cornea were highlighted as new findings of ODDD. Facial abnormalities were common in all affected members, but their fingers were normal. Severity of glaucoma was different among the affected individuals and seemed to depend on elevation of intraocular pressure, which occurred in narrow, but open-angle. Genetic analysis revealed the presence of c.119C>T (p.Ala40Val) in GJA1, which is responsible for ODDD, but not found in the control population. CONCLUSIONS: This report describes detailed ocular characteristics in a genetically confirmed ODDD family, including unreported findings of thick cornea and myopic refractive error despite short axial length. The ocular features derived from the A40V mutation in GJA1 showed complete penetrance, suggesting a possible role of Cx43 in regulation of IOP and pathogenesis of glaucoma.

Etiological trends in male central precocious puberty.

PURPOSE: In the present study, the etiological trends in male central precocious puberty (CPP) were examined, and annual distribution was evaluated. METHODS: Seventy-one male CPP subjects who started puberty before 9 years of age were included in this study. All individuals were diagnosed as having CPP at Samsung Medical Center between 2001 and 2016. Chronological age at puberty onset, diagnosis of CPP, bone age, weight (kg), height (cm), puberty stage, brain magnetic resonance imaging findings, testosterone level, basal gonadotropin level, and gonadotropin level after gonadotropin releasing hormone stimulation were analyzed. RESULTS: The 71 patients were divided into 2 groups: idiopathic (group I) and organic (group II) when the lesion was identified as associated with the central nervous system (CNS) or when the patient received chemotherapy for non-CNS tumors before CPP diagnosis, respectively. Forty-four cases (62%) were idiopathic, and 27 (38%) were organic. The proportion of idiopathic CPP was higher than that of organic CPP during the study period. In 51.9% of organic cases, puberty started before 8 years of age, whereas it started after that age in 93.2% of the idiopathic cases. CONCLUSION: In the present study, among all male CPP cases, 62% were idiopathic. The probability of idiopathic CPP prevalence was higher in males when the puberty onset was after 8 years of age with no history of cranial radiotherapy or chemotherapy.

Pycnodysostosis: Novel Variants in CTSK and Occurrence of Giant Cell Tumor.

Pycnodysostosis is an autosomal recessive skeletal dysplasia caused by pathogenic variants in the cathepsin K ( CTSK ) gene. We report seven patients from four unrelated families with this condition in whom we have identified three novel pathogenic variants, c.120 + 1G > T in intron 2, c.399 + 1G > A in intron 4, and c.148T > G (p.W50G) in exon 2, and a known variant, c.568C > T (p.Q190*) in exon 5 of CTSK . We present the clinical, radiographic, and molecular findings of all individuals with molecularly proven pycnodysostosis from the present cohort. We also report the occurrence of giant cell tumor in the skull of a patient with this condition.

A novel de novo mosaic mutation in PHEX in a Korean patient with hypophosphatemic rickets.

X-linked hypophosphatemic rickets is caused by loss-of-function mutations in PHEX, which encodes a phosphate-regulating endopeptidase homolog. We report a 26-year-old man with X-linked hypophosphatemic rickets who showed decreased serum phosphate accompanied by bilateral genu valgum and short stature. He had received medical treatment with vitamin D (alfacalcidol) and phosphate from the age of 3 to 20 years. He underwent surgery due to valgus deformity at the age of 14 and 15. Targeted gene panel sequencing for Mendelian genes identified a nonsense mutation in PHEX (c.589C>T; p.Gln197Ter) and a mosaic pattern where only 38% of sequence reads showed the variant allele. This mutation was not found in his mother, who had a normal phenotype. This is a case of a sporadic nonsense mutation in PHEX and up to date, this is the first case of a mosaic mutation in PHEX in Korea.

Oculodentodigital Dysplasia with a Novel Mutation in GJA1 Diagnosed by Targeted Gene Panel Sequencing: A Case Report and Literature Review.

Oculodentodigital dysplasia (ODDD; MIM #164200), a rare genetic disorder characterized by abnormal craniofacial, dental, ocular, and digital features, is caused by mutations in the gap junction alpha-1 (GJA1) gene. We report a case of a 6-year-old male who presented with dysmorphic facial features (short palpebral fissure, thin nose with hypoplastic alae nasi, and flat face), bilateral syndactyly, abnormal dentition, and proportionate short stature with growth hormone deficiency. A novel de novo heterozygous missense mutation (c.221A>C, p.H74P) in GJA1 was identified by targeted gene panel sequencing. This is the first case report of a novel ODDD-causing mutation in GJA1 confirmed by genetic analysis in Korea.

HDR syndrome with a novel mutation in GATA3 mimicking a congenital X-linked stapes gusher: a case report.

BACKGROUND: Hypoparathyroidism, sensorineural hearing loss, and renal disease (HDR) syndrome, also known as Barakat syndrome, is a rare genetic disorder with high phenotypic heterogeneity caused by haploinsufficiency of the GATA3 gene on chromosome 10p14-p15. For these reasons, the diagnosis of HDR syndrome is challenging and requires a high index of suspicion as well as genetic analysis. CASE PRESENTATION: A 14-month-old boy, with sensorineural hearing loss in both ears, showed typical radiological features of X-linked stapes gusher on preoperative temporal bone computed tomography (CT) for cochlear implantations. Then after his discharge from hospital, he suffered a hypocalcemic seizure and we discovered a renal cyst during investigation of hypocalcemia. He was finally diagnosed with HDR syndrome by clinical findings, which were confirmed by molecular genetic testing. Direct sequencing of the GATA3 gene showed a heterozygous 2-bp deletion (c.1201_1202delAT), which is predicted to cause a frameshift of the reading frame (p.Met401Valfs*106). CONCLUSIONS: To our knowledge, this is the first case of HDR syndrome with a novel de novo variant mimicking a congenital X-linked stapes gusher syndrome. Novel mutations and the diversity of clinical manifestations expand the genotypic and phenotypic spectrum of HDR syndrome. Diagnosis of HDR syndrome is still challenging, but clinicians should consider it in their differential diagnosis for children with a wide range of clinical manifestations including hypocalcemia induced seizures and deafness. We hope that this case will contribute to further understanding and studies of HDR-associated GATA3 mutations.

Further delineation of COG8-CDG: A case with novel compound heterozygous mutations diagnosed by targeted exome sequencing.

Congenital disorders of glycosylation (CDG) are a rapidly expanding group of inherited metabolic disorders with highly variable clinical presentations caused by deficient glycosylation of proteins and/or lipids. CDG-IIh is a very rare subgroup of CDG caused by mutations in the conserved oligomeric Golgi (COG) complex gene, COG8, and so far, only two cases have been reported in the medical literature. Here, we describe an 8-year-old Korean boy with psychomotor retardation, hypotonia, failure to thrive, elevated serum liver enzymes, microcephaly, and talipes equinovarus. A liver biopsy of the patient showed only interface hepatitis with mild lobular activity, and brain magnetic resonance imaging revealed cerebellar atrophy. Compared with the previous two reported cases, our patient showed relatively mild psychomotor retardation without a seizure history. The transferrin isoelectric focusing profiles in the patient showed a CDG type II pattern with increased disialo- and trisialo-transferrin. Targeted exome sequencing was performed to screen all CDG type II-related genes, and two novel frameshift mutations were found: c.171dupG (p.Leu58Alafs*29) and c.1656dupC (p.Ala553Argfs*15) in COG8. The parents were heterozygous carriers of each variant. CDG should be included in the initial differential diagnosis for children with a suspected unknown syndrome or unclassified inherited metabolic disorder or children with diverse clinical presentations, such as psychomotor retardation, hypotonia, skeletal deformity, microcephaly, cerebellar atrophy, and unexplained transient elevated liver enzyme.

Clinical and endocrine characteristics and genetic analysis of Korean children with McCune-Albright syndrome: a retrospective cohort study.

BACKGROUND: McCune-Albright syndrome (MAS) is a rare disease defined by the triad of fibrous dysplasia (FD), café au lait spots, and peripheral precocious puberty (PP). Because of the rarity of this disease, only a few individuals with MAS have been reported in Korea. We describe the various clinical and endocrine manifestations and genetic analysis of 14 patients with MAS in Korea. METHODS: Patients' clinical data-including peripheral PP, FD, and other endocrine problems-were reviewed retrospectively. In addition, treatment experiences of letrozole in five patients with peripheral PP were described. Mutant enrichment with 3'-modified oligonucleotides - polymerase chain reaction (MEMO-PCR) was performed on eight patients to detect mutation in GNAS using blood. MEMO-PCR is a simple and practical method that enables the nondestructive selection and enrichment of minor mutant alleles in blood. RESULTS: The median age at diagnosis was 5 years 2 months (range: 18 months to 16 years). Eleven patients were female, and three were male. Thirteen patients showed FD. All female patients showed peripheral PP at onset, and three patients subsequently developed central PP. There was a significant decrease in estradiol levels after two years of letrozole treatment. However, bone age was advanced in four patients. Two patients had clinical hyperthyroidism, and two patients had growth hormone (GH) excess with pituitary microadenoma. c.602G > A (p.Arg201His) in GNAS was detected in two patients in blood, and c.601C > T (p.Arg201Cys) in GNAS was detected in one patient in pituitary adenoma. CONCLUSIONS: This study described the various clinical manifestations of 14 patients with MAS in a single center in Korea. This study first applied MEMO-PCR on MAS patients to detect GNAS mutation. Because a broad spectrum of endocrine manifestations could be found in MAS, multiple endocrinopathies should be monitored in MAS patients. Better treatment options for peripheral PP with MAS are needed.

BGN Mutations in X-Linked Spondyloepimetaphyseal Dysplasia.

Spondyloepimetaphyseal dysplasias (SEMDs) comprise a heterogeneous group of autosomal-dominant and autosomal-recessive disorders. An apparent X-linked recessive (XLR) form of SEMD in a single Italian family was previously reported. We have been able to restudy this family together with a second family from Korea by segregating a severe SEMD in an X-linked pattern. Exome sequencing showed missense mutations in BGN c.439A>G (p.Lys147Glu) in the Korean family and c.776G>T (p.Gly259Val) in the Italian family; the c.439A>G (p.Lys147Glu) mutation was also identified in a further simplex SEMD case from India. Biglycan is an extracellular matrix proteoglycan that can bind transforming growth factor beta (TGF-ß) and thus regulate its free concentration. In 3-dimensional simulation, both altered residues localized to the concave arc of leucine-rich repeat domains of biglycan that interact with TGF-ß. The observation of recurrent BGN mutations in XLR SEMD individuals from different ethnic backgrounds allows us to define "XLR SEMD, BGN type" as a nosologic entity.

Arnold Chiari Malformation With Sponastrime (Spondylar and Nasal Changes, With Striations of the Metaphyses) Dysplasia: A Case Report.

SPOndylar and NAsal changes, with STRIations of the Metaphyses (SPONASTRIME) dysplasia (SD) is a dwarfing autosomal recessive syndrome, characterized by a variety of clinical and radiographic features, which form the basis for diagnosis. We describe the presentation of an Arnold Chiari malformation in a patient with a clinical diagnosis of SD. The malformation was successfully treated by decompression of the foramen magnum and elevation of the cerebellum, with complete resolution of pain.We report a rare case of Arnold Chiari malformation in a patient presenting with clinical and radiographic features strongly suggestive of SD and be successfully treated.

Estrogen-mediated Height Control in Girls with Marfan Syndrome.

This study evaluated the efficacy of a stepwise regimen of estradiol valerate for height control in girls with Marfan syndrome. Eight girls with Marfan syndrome who had completed estrogen treatment for height control were included. Estradiol valerate was started at a dose of 2 mg/day, and then was increased. The projected final height was estimated using the initial height percentile (on a disease-specific growth curve for Korean Marfan syndrome [gcPFHt]), and the initial bone age (baPFHt). After the estrogen treatment, the projected final height was compared to the actual final height (FHt). The median baseline chronological and bone age were 10.0 and 10.5 years, respectively. After a median of 36.5 months of treatment, the median FHt (172.6 cm) was shorter than the median gcPFHt (181.0 cm) and baPFHt (175.9 cm). In the six patients who started treatment before the age of 11 years, the median FHt (171.8 cm) was shorter than the median gcPFHt (181.5 cm) and baPFHt (177.4 cm) after treatment. The median differences between the FHt and gcPFHt and baPFHt were 9.2 and 8.3 cm, respectively. In two patients started treatment after the age of 11, the differences between FHt and gcPFHt, and baPFHt after treatment were -4 and 1.4 cm, and -1.2 and 0 cm for each case, respectively. A stepwise increasing regimen of estradiol valerate may be an effective treatment for height control in girls with Marfan syndrome, especially when started under 11 years old.