Williams syndrome (WS) is a well-recognized neurodevelopmental disorder manifested by both connec... more Williams syndrome (WS) is a well-recognized neurodevelopmental disorder manifested by both connective tissue and CNS abnormalities. The study depicts the 8-y experience and follow-up of 50 Greek children with the clinical diagnosis of WS. Clinical data on the facial features and cardiovascular, endocrinologic, and neurodevelopmental evaluation are presented. The most consistent findings were dysmorphic features (100%), followed by dental anomalies (90%) and hyperacousis (90%). Only eight of 50 children had severe cardiovascular defects that required surgical intervention during the first year of life. Supravalvular aortic stenosis was less frequent (28%) than shown in the literature. Severe hypertension was noticed in 22% of our patients, and infantile hypercalcemia was noticed in 6%. Twelve percent of our patients showed an elevation of CPK. Most children presented with moderate to severe mental retardation with IQ ranging from 20 to 85. Elastin hemizygosity was detected by fluorescence in situ hybridization. Dinucleotide repeat polymorphism analysis was performed in an attempt to correlate phenotype with genotype. The origin of deletions was more frequently maternal (59%), and a more severe phenotype seemed to be associated with those deletions. This is the first report on WS patients in the Greek population. (Pediatr Res 57: 789-795, 2005) Abbreviations BMI, body mass index DNRP, dinucleotide repeat polymorphism FISH, fluorescence in situ hybridization LCR, low-copy repeat PS, pulmonary stenosis RFLP, restriction fragment length polymorphism SVAS, supravalvular aortic stenosis WS, Williams syndrome
A case of a novel in-frame FLNB deletion in familiar Larsen syndrome of a newborn, with a clinica... more A case of a novel in-frame FLNB deletion in familiar Larsen syndrome of a newborn, with a clinical appearance of dislocated bilateral hip joints, knee joints, elbows and equinovarus foot deformities. Patient underwent both conservative treatment and surgical treatment in sequence of severity as indicated, while in parallel genetic counseling with subsequent DNA testing revealed the familiar extent of the syndrome and a novel mutation first reported today. Patient follow up is presented until adulthood giving a great insight to the impact of the treatment chosen at presentation.
Mutations and deletions of the NSD1 gene, located on chromosome 5q35, are responsible for over 90... more Mutations and deletions of the NSD1 gene, located on chromosome 5q35, are responsible for over 90% of cases of Sotos syndrome. Fluorescent in situ hybridization analysis (FISH), MLPA or multiplex quantitative PCR allow detection of total/partial NSD1 deletions and direct sequencing allows detection of NSD1 mutations. We describe two boys with Sotos syndrome in whom PCR amplification and direct sequencing of the NSD1 gene identified two novel mutations not previously described: c.4736dupG in exon 12 and c.3938_3939insT in exon 7. In addition to the cardinal and major features of the syndrome (abnormal facial appearance, overgrowth, cardiac anomalies, renal anomalies, hypotonia, neonatal jaundice, seizures and brain MRI abnormalities) in both patients, one boy also had cryptorchidism and vertebral anomalies, features considered not common. Despite the wide range of possible combinations of phenotypic features, molecular analysis can correctly identify Sotos syndrome.
Journal of Pediatric Endocrinology and Metabolism, Jan 28, 2016
The 22q13 deletion syndrome or Phelan-McDermid syndrome is a neurodevelopmental disorder associat... more The 22q13 deletion syndrome or Phelan-McDermid syndrome is a neurodevelopmental disorder associated with developmental delay, hypotonia, delayed or absent speech, autistic-like behavior, normal to accelerated growth and dysmorphic faces. We report the occurrence of central precocious puberty in a boy diagnosed with Phelan-McDermid syndrome. At the age of 1 year, our patient presented with increased testicular volume for his age, bone age advancement and growth acceleration. Stimulated gonadotropin levels demonstrated a premature activation of the hypothalamic-pituitary-gonadal (HPG) axis. Central precocious puberty was treated with gonadotropin-releasing hormone (GnRH) analog. Molecular diagnosis with array-comparative genomic hybridization (CGH) revealed a major deletion of 5.8 Mb at the 22q13 chromosomal region and a 25 kb duplication at the 9q34.3 region that included the NOTCH-1 gene. On the background of 22q13 deletion syndrome and data from animals on the effect of abnormal NOTCH-1 gene expression on kisspeptin neuron formation, we discuss the probable role of Notch signaling in the premature activation of the HPG axis.
Goldenhar (GS) syndrome is a well-recognised developmental disorder involving first and second br... more Goldenhar (GS) syndrome is a well-recognised developmental disorder involving first and second branchial arches and characterized by considerable phenotypic variability. The present study presents clinical data on the morphologic features, hearing, ophthalmologic, orthopaedic, neurological, cardiovascular, genitourinary and gastrointestinal evaluation of 17 Greek patients (one pair of monozygotic twins) aged 20 days to 23 years with the clinical diagnosis of GS and with a normal karyotype. The most consistent findings were auricular defects (94%), followed by facial (76%) and ocular anomalies (65%), 70% unilateral, mainly right-sided. In the majority of our patients (90%) mandibular hypoplasia was ipsilateral to the dysplastic ear or the most severely affected ear in bilateral cases. Hearing loss, mainly conductive, was noted in 76% of our patients. Skeletal defects were evident in 23%, while cardiovascular, genitourinary and gastrointestinal in 18%, 23% and 12% respectively. The most frequent neurological manifestation was facial nerve paralysis (12%), while the incidence of mental retardation was higher (23%) than reported in the literature, presumably attributed to the severe hearing and vision loss. In a pair of monozygotic twins of our study discordance of clinical findings was noted. Precise evaluation of GS patients and multidisciplinary care management is necessary to avoid possible complications of many systems and to offer appropriate genetic counselling to the family.
... Helen Fryssira1 Artemis Tsitsika, MD2 Athanassia Lourida Nina Manolaki2 1Medical Genetics, Un... more ... Helen Fryssira1 Artemis Tsitsika, MD2 Athanassia Lourida Nina Manolaki2 1Medical Genetics, University of Athens Medical School, “Aghia Sophia” Children's Hospital; 21st Department of Pediatrics, University of Athens, “Aghia Sophia” Children's Hospital, Athens, Greece. ...
Cohen syndrome is a rare genetic disorder consisting of truncal obesity, hypotonia, mental retard... more Cohen syndrome is a rare genetic disorder consisting of truncal obesity, hypotonia, mental retardation, characteristic facial appearance and ocular anomalies. Other diagnostic clinical features include narrow hands and feet, low growth parameters, neutropenia and chorioretinal dystrophy. We describe the similarities in the clinical and developmental pro®le of two siblings with Cohen syndrome, providing evidence for autosomal recessive inheritance in this condition. Conclusion The diagnosis of Cohen syndrome should be suspected in mentally retarded children with the above characteristics. Neutropenia and ocular anomalies with highgrade myopia and chorioretinal dystrophy are also considered important ®ndings and can aid in the clinical diagnosis especially at an early age.
Noonan syndrome (NS) is a common multiple congenital anomaly entity, the diagnosis of which, on c... more Noonan syndrome (NS) is a common multiple congenital anomaly entity, the diagnosis of which, on clinical grounds, is based on a comprehensive scoring system in order to select patients for molecular confirmation. Our aim was to evaluate the phenotypic characteristics in the light of PTPN11 mutations. The study revealed 80 patients who were referred with initial indication of NS or Noonan-like syndrome (NLS) and further assessed by a clinical geneticist; 60/80 index patients, mean age 5.9 ± 5.3 years, fulfilled the NS criteria. Molecular analysis of PTPN11 gene (exons and their flanking regions) of the total population revealed mutations in 17/80 patients, all belonging in the group of the patients screened with the scoring system. All mutations were heterozygous missense changes, mostly clustering in exon 3 (8/17), followed by exons 13 (3/17), 8 (2/17), 7 (2/17), 2 (1/17) and 4 (1/17). We conclude that (a) most of our clinically diagnosed NS cases were sporadic (b) PTPN11 analysis should be limited to those fulfilling the relevant NS criteria (c) Cardiovascular evaluation should comprise all NS patients, while pulmonary stenosis, short stature, and thorax deformities prevailed among those with PTPN11 mutations.
In SMA, unusual findings such as deletions restricted only to SMN1 exon 8, inspite of honozygous ... more In SMA, unusual findings such as deletions restricted only to SMN1 exon 8, inspite of honozygous SMN1 exons 7e8 deletions in the family, may obscure final diagnosis. Application of a modified PCR procedure allowed discrimination between a deletion or a gene conversion event in a case of prenatal diagnosis.
Facioscapulohumeral Muscular Dystrophy (FSHD) is a genetic myopathy with a remarkable intra-and i... more Facioscapulohumeral Muscular Dystrophy (FSHD) is a genetic myopathy with a remarkable intra-and inter-familial clinical heterogeneity. This study reports the clinical and genetic analysis of 133 individuals from 71 unrelated Greek families based on a revised Clinical Severity Score (rCSS) index which was developed for clinical assessment regarding the disease progression. A high ratio (31/62, 50%) of probands' family members was found to be asymptomatic or minimally affected gene carriers of a contracted 4q allele. Moreover, a notable clinical variability of FSHD is reported concerning the detection of an identical de novo 13 kb EcoRI fragment in monozygotic twins, as well as indications of founder effect. This is the first survey that presents data of FSHD families from an East Mediterranean country supporting the speculation that the prevalence of disease might be significantly underestimated and that synergistic factors could play an essential role on the progression of the disease.
Non-Hodgkin lymphoma in an 8-year-old boy with Williams syndrome is reported. Molecular DNA analy... more Non-Hodgkin lymphoma in an 8-year-old boy with Williams syndrome is reported. Molecular DNA analysis showed a maternal deletion at 7q11.23, the locus of elastin and several other genes, including the BCL7B gene, involved in early development. To our knowledge, this is the second reported case of a lymphoma in a Williams syndrome patient and the first in a child.
Journal of Autism and Developmental Disorders, Apr 9, 2019
Myhre syndrome (MS) is a connective tissue disorder with multisystem involvement with or without ... more Myhre syndrome (MS) is a connective tissue disorder with multisystem involvement with or without intellectual disability. In most cases SMAD4 mutations are reported. To date, 55 individuals have been molecularly confirmed. Autism has been proposed among associate clinical features of MS but no standardized diagnosis was available in previous cases. We report a case of a 25-year-old man with a pathogenic heterozygous SMAD4 missense mutation affecting residue Arg 496 (SMAD4:p. Arg496Cys). Clinical findings are consistent with MS, commorbid with affective disorder and High Functioning Autism Spectrum Disorder confirmed by a standardized assessment procedure. The thorough clinical assessment of cases with syndromes such as MS can extend our knowledge on both the phenotypic characteristics of the syndrome and the genetic basis of autism. Keywords Myhre syndrome • SMAD4 mutation • High functioning autism spectrum disorder • Affective disorder Myhre et al. (1981) were the first to report two unrelated males with mental retardation, facial dysmorphism, short stature, brachydactyly, muscle hypertrophy, decreased joint mobility, mixed hearing loss, and cleft lip and palate in one of them. Facial dysmorphism included short palpebral fissures, maxillary hypoplasia, prognathism, short philtrum, and small mouth. Le Goff et al. (2012) identified missense SMAD4 heterozygous mutations, affecting the conserved Ile 500 residue as a cause in 11 individuals with Myhre syndrome (MS). Shortly after Caputo et al. (2012) reported another eight MS cases with similar SMAD4 mutations. To date, 55 individuals have been molecularly confirmed with MS (Starr et al. 2017). The syndrome is considered a
Journal of Pediatric Endocrinology and Metabolism, 2005
Pre- and postnatal growth retardation of unknown pathogenesis is a common clinical feature in pat... more Pre- and postnatal growth retardation of unknown pathogenesis is a common clinical feature in patients with Williams-Beuren syndrome (WBS). However, growth hormone deficiency (GHD) has not been considered a major cause of growth retardation. There is only one patient in the literature with confirmed GHD who responded well to human growth hormone (hGH) therapy. We report a female infant with confirmed WBS who, through provocative testing, was found to have GHD and who responded satisfactorily to hGH therapy. Height SDS was -4.2 at the age of 12 months when hGH was initiated and increased to -0.8 at the age of 4.25 years. The pathogenesis of GHD in our patient is unclear. Nevertheless, the elevated levels of prolactin and the response of hGH to growth hormone releasing hormone (GHRH) administration are indicative of a hypothalamic rather than pituitary defect. In conclusion, GH deficiency might contribute to the growth failure in a number of patients with WBS and in such cases hGH therapy will most likely improve final height.
Williams syndrome (WS) is a well-recognized neurodevelopmental disorder manifested by both connec... more Williams syndrome (WS) is a well-recognized neurodevelopmental disorder manifested by both connective tissue and CNS abnormalities. The study depicts the 8-y experience and follow-up of 50 Greek children with the clinical diagnosis of WS. Clinical data on the facial features and cardiovascular, endocrinologic, and neurodevelopmental evaluation are presented. The most consistent findings were dysmorphic features (100%), followed by dental anomalies (90%) and hyperacousis (90%). Only eight of 50 children had severe cardiovascular defects that required surgical intervention during the first year of life. Supravalvular aortic stenosis was less frequent (28%) than shown in the literature. Severe hypertension was noticed in 22% of our patients, and infantile hypercalcemia was noticed in 6%. Twelve percent of our patients showed an elevation of CPK. Most children presented with moderate to severe mental retardation with IQ ranging from 20 to 85. Elastin hemizygosity was detected by fluorescence in situ hybridization. Dinucleotide repeat polymorphism analysis was performed in an attempt to correlate phenotype with genotype. The origin of deletions was more frequently maternal (59%), and a more severe phenotype seemed to be associated with those deletions. This is the first report on WS patients in the Greek population. (Pediatr Res 57: 789-795, 2005) Abbreviations BMI, body mass index DNRP, dinucleotide repeat polymorphism FISH, fluorescence in situ hybridization LCR, low-copy repeat PS, pulmonary stenosis RFLP, restriction fragment length polymorphism SVAS, supravalvular aortic stenosis WS, Williams syndrome
A case of a novel in-frame FLNB deletion in familiar Larsen syndrome of a newborn, with a clinica... more A case of a novel in-frame FLNB deletion in familiar Larsen syndrome of a newborn, with a clinical appearance of dislocated bilateral hip joints, knee joints, elbows and equinovarus foot deformities. Patient underwent both conservative treatment and surgical treatment in sequence of severity as indicated, while in parallel genetic counseling with subsequent DNA testing revealed the familiar extent of the syndrome and a novel mutation first reported today. Patient follow up is presented until adulthood giving a great insight to the impact of the treatment chosen at presentation.
Mutations and deletions of the NSD1 gene, located on chromosome 5q35, are responsible for over 90... more Mutations and deletions of the NSD1 gene, located on chromosome 5q35, are responsible for over 90% of cases of Sotos syndrome. Fluorescent in situ hybridization analysis (FISH), MLPA or multiplex quantitative PCR allow detection of total/partial NSD1 deletions and direct sequencing allows detection of NSD1 mutations. We describe two boys with Sotos syndrome in whom PCR amplification and direct sequencing of the NSD1 gene identified two novel mutations not previously described: c.4736dupG in exon 12 and c.3938_3939insT in exon 7. In addition to the cardinal and major features of the syndrome (abnormal facial appearance, overgrowth, cardiac anomalies, renal anomalies, hypotonia, neonatal jaundice, seizures and brain MRI abnormalities) in both patients, one boy also had cryptorchidism and vertebral anomalies, features considered not common. Despite the wide range of possible combinations of phenotypic features, molecular analysis can correctly identify Sotos syndrome.
Journal of Pediatric Endocrinology and Metabolism, Jan 28, 2016
The 22q13 deletion syndrome or Phelan-McDermid syndrome is a neurodevelopmental disorder associat... more The 22q13 deletion syndrome or Phelan-McDermid syndrome is a neurodevelopmental disorder associated with developmental delay, hypotonia, delayed or absent speech, autistic-like behavior, normal to accelerated growth and dysmorphic faces. We report the occurrence of central precocious puberty in a boy diagnosed with Phelan-McDermid syndrome. At the age of 1 year, our patient presented with increased testicular volume for his age, bone age advancement and growth acceleration. Stimulated gonadotropin levels demonstrated a premature activation of the hypothalamic-pituitary-gonadal (HPG) axis. Central precocious puberty was treated with gonadotropin-releasing hormone (GnRH) analog. Molecular diagnosis with array-comparative genomic hybridization (CGH) revealed a major deletion of 5.8 Mb at the 22q13 chromosomal region and a 25 kb duplication at the 9q34.3 region that included the NOTCH-1 gene. On the background of 22q13 deletion syndrome and data from animals on the effect of abnormal NOTCH-1 gene expression on kisspeptin neuron formation, we discuss the probable role of Notch signaling in the premature activation of the HPG axis.
Goldenhar (GS) syndrome is a well-recognised developmental disorder involving first and second br... more Goldenhar (GS) syndrome is a well-recognised developmental disorder involving first and second branchial arches and characterized by considerable phenotypic variability. The present study presents clinical data on the morphologic features, hearing, ophthalmologic, orthopaedic, neurological, cardiovascular, genitourinary and gastrointestinal evaluation of 17 Greek patients (one pair of monozygotic twins) aged 20 days to 23 years with the clinical diagnosis of GS and with a normal karyotype. The most consistent findings were auricular defects (94%), followed by facial (76%) and ocular anomalies (65%), 70% unilateral, mainly right-sided. In the majority of our patients (90%) mandibular hypoplasia was ipsilateral to the dysplastic ear or the most severely affected ear in bilateral cases. Hearing loss, mainly conductive, was noted in 76% of our patients. Skeletal defects were evident in 23%, while cardiovascular, genitourinary and gastrointestinal in 18%, 23% and 12% respectively. The most frequent neurological manifestation was facial nerve paralysis (12%), while the incidence of mental retardation was higher (23%) than reported in the literature, presumably attributed to the severe hearing and vision loss. In a pair of monozygotic twins of our study discordance of clinical findings was noted. Precise evaluation of GS patients and multidisciplinary care management is necessary to avoid possible complications of many systems and to offer appropriate genetic counselling to the family.
... Helen Fryssira1 Artemis Tsitsika, MD2 Athanassia Lourida Nina Manolaki2 1Medical Genetics, Un... more ... Helen Fryssira1 Artemis Tsitsika, MD2 Athanassia Lourida Nina Manolaki2 1Medical Genetics, University of Athens Medical School, “Aghia Sophia” Children's Hospital; 21st Department of Pediatrics, University of Athens, “Aghia Sophia” Children's Hospital, Athens, Greece. ...
Cohen syndrome is a rare genetic disorder consisting of truncal obesity, hypotonia, mental retard... more Cohen syndrome is a rare genetic disorder consisting of truncal obesity, hypotonia, mental retardation, characteristic facial appearance and ocular anomalies. Other diagnostic clinical features include narrow hands and feet, low growth parameters, neutropenia and chorioretinal dystrophy. We describe the similarities in the clinical and developmental pro®le of two siblings with Cohen syndrome, providing evidence for autosomal recessive inheritance in this condition. Conclusion The diagnosis of Cohen syndrome should be suspected in mentally retarded children with the above characteristics. Neutropenia and ocular anomalies with highgrade myopia and chorioretinal dystrophy are also considered important ®ndings and can aid in the clinical diagnosis especially at an early age.
Noonan syndrome (NS) is a common multiple congenital anomaly entity, the diagnosis of which, on c... more Noonan syndrome (NS) is a common multiple congenital anomaly entity, the diagnosis of which, on clinical grounds, is based on a comprehensive scoring system in order to select patients for molecular confirmation. Our aim was to evaluate the phenotypic characteristics in the light of PTPN11 mutations. The study revealed 80 patients who were referred with initial indication of NS or Noonan-like syndrome (NLS) and further assessed by a clinical geneticist; 60/80 index patients, mean age 5.9 ± 5.3 years, fulfilled the NS criteria. Molecular analysis of PTPN11 gene (exons and their flanking regions) of the total population revealed mutations in 17/80 patients, all belonging in the group of the patients screened with the scoring system. All mutations were heterozygous missense changes, mostly clustering in exon 3 (8/17), followed by exons 13 (3/17), 8 (2/17), 7 (2/17), 2 (1/17) and 4 (1/17). We conclude that (a) most of our clinically diagnosed NS cases were sporadic (b) PTPN11 analysis should be limited to those fulfilling the relevant NS criteria (c) Cardiovascular evaluation should comprise all NS patients, while pulmonary stenosis, short stature, and thorax deformities prevailed among those with PTPN11 mutations.
In SMA, unusual findings such as deletions restricted only to SMN1 exon 8, inspite of honozygous ... more In SMA, unusual findings such as deletions restricted only to SMN1 exon 8, inspite of honozygous SMN1 exons 7e8 deletions in the family, may obscure final diagnosis. Application of a modified PCR procedure allowed discrimination between a deletion or a gene conversion event in a case of prenatal diagnosis.
Facioscapulohumeral Muscular Dystrophy (FSHD) is a genetic myopathy with a remarkable intra-and i... more Facioscapulohumeral Muscular Dystrophy (FSHD) is a genetic myopathy with a remarkable intra-and inter-familial clinical heterogeneity. This study reports the clinical and genetic analysis of 133 individuals from 71 unrelated Greek families based on a revised Clinical Severity Score (rCSS) index which was developed for clinical assessment regarding the disease progression. A high ratio (31/62, 50%) of probands' family members was found to be asymptomatic or minimally affected gene carriers of a contracted 4q allele. Moreover, a notable clinical variability of FSHD is reported concerning the detection of an identical de novo 13 kb EcoRI fragment in monozygotic twins, as well as indications of founder effect. This is the first survey that presents data of FSHD families from an East Mediterranean country supporting the speculation that the prevalence of disease might be significantly underestimated and that synergistic factors could play an essential role on the progression of the disease.
Non-Hodgkin lymphoma in an 8-year-old boy with Williams syndrome is reported. Molecular DNA analy... more Non-Hodgkin lymphoma in an 8-year-old boy with Williams syndrome is reported. Molecular DNA analysis showed a maternal deletion at 7q11.23, the locus of elastin and several other genes, including the BCL7B gene, involved in early development. To our knowledge, this is the second reported case of a lymphoma in a Williams syndrome patient and the first in a child.
Journal of Autism and Developmental Disorders, Apr 9, 2019
Myhre syndrome (MS) is a connective tissue disorder with multisystem involvement with or without ... more Myhre syndrome (MS) is a connective tissue disorder with multisystem involvement with or without intellectual disability. In most cases SMAD4 mutations are reported. To date, 55 individuals have been molecularly confirmed. Autism has been proposed among associate clinical features of MS but no standardized diagnosis was available in previous cases. We report a case of a 25-year-old man with a pathogenic heterozygous SMAD4 missense mutation affecting residue Arg 496 (SMAD4:p. Arg496Cys). Clinical findings are consistent with MS, commorbid with affective disorder and High Functioning Autism Spectrum Disorder confirmed by a standardized assessment procedure. The thorough clinical assessment of cases with syndromes such as MS can extend our knowledge on both the phenotypic characteristics of the syndrome and the genetic basis of autism. Keywords Myhre syndrome • SMAD4 mutation • High functioning autism spectrum disorder • Affective disorder Myhre et al. (1981) were the first to report two unrelated males with mental retardation, facial dysmorphism, short stature, brachydactyly, muscle hypertrophy, decreased joint mobility, mixed hearing loss, and cleft lip and palate in one of them. Facial dysmorphism included short palpebral fissures, maxillary hypoplasia, prognathism, short philtrum, and small mouth. Le Goff et al. (2012) identified missense SMAD4 heterozygous mutations, affecting the conserved Ile 500 residue as a cause in 11 individuals with Myhre syndrome (MS). Shortly after Caputo et al. (2012) reported another eight MS cases with similar SMAD4 mutations. To date, 55 individuals have been molecularly confirmed with MS (Starr et al. 2017). The syndrome is considered a
Journal of Pediatric Endocrinology and Metabolism, 2005
Pre- and postnatal growth retardation of unknown pathogenesis is a common clinical feature in pat... more Pre- and postnatal growth retardation of unknown pathogenesis is a common clinical feature in patients with Williams-Beuren syndrome (WBS). However, growth hormone deficiency (GHD) has not been considered a major cause of growth retardation. There is only one patient in the literature with confirmed GHD who responded well to human growth hormone (hGH) therapy. We report a female infant with confirmed WBS who, through provocative testing, was found to have GHD and who responded satisfactorily to hGH therapy. Height SDS was -4.2 at the age of 12 months when hGH was initiated and increased to -0.8 at the age of 4.25 years. The pathogenesis of GHD in our patient is unclear. Nevertheless, the elevated levels of prolactin and the response of hGH to growth hormone releasing hormone (GHRH) administration are indicative of a hypothalamic rather than pituitary defect. In conclusion, GH deficiency might contribute to the growth failure in a number of patients with WBS and in such cases hGH therapy will most likely improve final height.
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Papers by Helen Fryssira