Branding of subjects affected with genetic syndromes of severe short stature in developing countries

In Ecuador, a developing South American country, subjects affected with genetic syndromes of severe short stature are commonly referred to as dwarfs or midgets. Furthermore, and because in earlier studies some patients had evidenced mental retardation, such abnormality is assumed to exist in all affected subjects. Herein, we present two discrete instances in which this type of branding occurs. The first is that of individuals with Laron syndrome who are still called ‘dwarfs’ and considered as having a degree of mental retardation despite evidence showing otherwise. A similar problem, that of a girl affected with a genetic syndrome of short stature, which might include mental retardation, is also discussed. Considering that stigmatising is a form of discrimination, it concerns us all. Hence, the use of derogatory terms such as midget, dwarf or cretin, that might unintentionally occur even when delivering the best and most devoted medical care, must be eliminated.

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Branding of subjects affected with genetic syndromes of severe short stature in developing countries

Yearbook of Paediatric Endocrinology ◽

10.1530/ey.17.13.5 ◽

2020 ◽

Author(s):

Guevara-Aguirre J ◽

Guevara C ◽

Guevara A ◽

Gavilanes AA

Keyword(s):

Developing Countries ◽

Short Stature ◽

Genetic Syndromes ◽

Severe Short Stature

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Same Phenotype in Children with Growth Hormone Deficiency and Resistance

Case Reports in Pediatrics ◽

10.1155/2018/5902835 ◽

2018 ◽

Vol 2018 ◽

pp. 1-4

Author(s):

Irene Ioimo ◽

Carmen Guarracino ◽

Cristina Meazza ◽

Horacio M. Domené ◽

Mauro Bozzola

Keyword(s):

Short Stature ◽

Pcr Amplification ◽

Hormone Deficiency ◽

Saddle Nose ◽

Laron Syndrome ◽

First Case ◽

Igf I ◽

Undetectable Serum ◽

Type Ia ◽

Severe Short Stature

By definition, about 2.5% of children show a short stature due to several causes. Two clinical conditions are characterized by serum IGF-I low levels, idiopathic GH deficiency (IGHD), and GH insensitivity (GHI), and the phenotypic appearance of these patients may be very similar. We studied two children with short stature and similar phenotypes. The first case showed frontal bossing, doll face, acromicria, and truncal obesity, with a GH peak <0.05 ng/ml after stimuli and undetectable serum IGF-I levels. After PCR amplification of the whole GH1 gene, type IA idiopathic GHD was diagnosed. The second case had cranium hypoplasia, a large head, protruding forehead, saddle nose, underdeveloped mandible, and a micropenis. Basal GH levels were high (28.4 ng/ml) while serum IGF-I levels were low and unchangeable during the IGF-I generation test. Laron syndrome was confirmed after the molecular analysis of the GH receptor (GHR) gene. IGHD type IA and Laron syndrome is characterized by opposite circulating levels of GH, while both have reduced levels of IGF-I, with an overlapping clinical phenotype, lacking the effects of IGF-I on cartilage. These classical cases show the importance of differential diagnosis in children with severe short stature.

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Laron syndrome in three female siblings with the development of subclinical hypothyroidism and dyslipidemia in one case: first report of a Syrian family

Oxford Medical Case Reports ◽

10.1093/omcr/omab079 ◽

2021 ◽

Vol 2021 (9) ◽

Author(s):

Ahmad Chreitah ◽

Kheria Hijazia ◽

Leen Jamel Doya

Keyword(s):

Short Stature ◽

Subclinical Hypothyroidism ◽

Autosomal Recessive ◽

Index Case ◽

Autosomal Recessive Disorder ◽

Facial Features ◽

Laron Syndrome ◽

High Clinical Suspicion ◽

Facial Phenotype ◽

Severe Short Stature

ABSTRACT Laron syndrome (LS) is a rare autosomal recessive disorder characterized by dwarfism and typical facial phenotype. This report is the first to present three cases of Laron syndrome affecting three female siblings from Syria. The index case presented at age of 8.5 years with severe short stature: low level of Insulin-like growth factor 1 (IGF-1), elevated levels of fasting and post-stimulation growth hormone (GH), consistent with the diagnosis of Laron syndrome. At the age of 9.5 years, she developed non-autoimmune subclinical hypothyroidism treated with Levothyroxine, then she developed dyslipidemia at the age of 11.3 years. Later, we identified two female siblings of the patient with Laron syndrome. Laron syndrome is a rare genetic disease, reporting of new cases of this rare syndrome must encourage pediatricians to develop high clinical suspicion if faced with patients with very short stature and typical facial features.

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X-linked mental retardation and severe short stature with a novel mutation of the KDM5C gene

Clinical Pediatric Endocrinology ◽

10.1297/cpe.30.61 ◽

2021 ◽

Vol 30 (1) ◽

pp. 61-64

Author(s):

Fumika Kawano-Matsuda ◽

Tomoki Maeda ◽

Tadashi Kaname ◽

Kumiko Yanagi ◽

Kenji Ihara

Keyword(s):

Mental Retardation ◽

Short Stature ◽

Novel Mutation ◽

Severe Short Stature ◽

I Gene

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Severe short stature, hyperphalangy of the index fingers, mental retardation and facial dysmorphism

Clinical Dysmorphology ◽

10.1097/00019605-200009020-00007 ◽

2000 ◽

Vol 9 (2) ◽

pp. 111-114 ◽

Cited By ~ 3

Author(s):

K. Devriendt ◽

K. Keymolen ◽

L. Roelen ◽

G. Van Goethem ◽

J. Meireleire ◽

...

Keyword(s):

Mental Retardation ◽

Short Stature ◽

Facial Dysmorphism ◽

Severe Short Stature

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Language in mental retardation: Individual and syndromic differences, and neurogenetic variation 1Based on a keynote presentation at the Third European Conference on Psychological Theory and Research in Mental Retardation, Geneva, September 1st, 2000.

Swiss Journal of Psychology ◽

10.1024//1421-0185.60.3.161 ◽

2001 ◽

Vol 60 (3) ◽

pp. 161-178 ◽

Cited By ~ 23

Author(s):

Jean A. Rondal

Keyword(s):

Mental Retardation ◽

Language Development ◽

Oral Language ◽

Psychological Theory ◽

Genetic Syndromes ◽

Explanatory Variables ◽

Keynote Presentation ◽

Genetic Origins ◽

The Sixties ◽

The Individual

Predominantly non-etiological conceptions have dominated the field of mental retardation (MR) since the discovery of the genetic etiology of Down syndrome (DS) in the sixties. However, contemporary approaches are becoming more etiologically oriented. Important differences across MR syndromes of genetic origin are being documented, particularly in the cognition and language domains, differences not explicable in terms of psychometric level, motivation, or other dimensions. This paper highlights the major difficulties observed in the oral language development of individuals with genetic syndromes of mental retardation. The extent of inter- and within-syndrome variability are evaluated. Possible brain underpinnings of the behavioural differences are envisaged. Cases of atypically favourable language development in MR individuals are also summarized and explanatory variables discussed. It is suggested that differences in brain architectures, originating in neurological development and having genetic origins, may largely explain the syndromic as well as the individual within-syndrome variability documented. Lastly, the major implications of the above points for current debates about modularity and developmental connectionism are spelt out.

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Growth hormone therapy in a child with severe short stature due to Miller-McKusick-Malvaux (3M) syndrome-2

Bone Abstracts ◽

10.1530/boneabs.7.p139 ◽

2019 ◽

Author(s):

Sumudu Seneviratne ◽

Deepthi de Silva ◽

Emily Cottrell ◽

Piumi Kuruppu ◽

KSH de Silva ◽

...

Keyword(s):

Growth Hormone ◽

Hormone Therapy ◽

Short Stature ◽

Growth Hormone Therapy ◽

Severe Short Stature

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Autoimmunity and Genetic Syndromes: A Focus on Down Syndrome

Genes ◽

10.3390/genes12020268 ◽

2021 ◽

Vol 12 (2) ◽

pp. 268

Author(s):

Marta Ferrari ◽

Stefano Stagi

Keyword(s):

Down Syndrome ◽

Autoimmune Diseases ◽

Normal Population ◽

Underlying Mechanism ◽

Short Review ◽

Immune Dysregulation ◽

Infectious Complications ◽

Genetic Syndromes ◽

Genetic Syndrome

Within immune system-related diseases, autoimmunity has always represented a field of great interest, although many aspects remain poorly understood even today. Genetic syndromes associated with immunity disorders are common and represent an interesting model for a better understanding of the underlying mechanism of autoimmunity predisposition. Among these conditions, Down syndrome (DS) certainly deserves special attention as it represents the most common genetic syndrome associated with immune dysregulation, involving both innate and adaptive immunity. Autoimmunity represents a well-known complication of DS: it is estimated that people affected by this disease present a risk four to six times higher than the normal population to develop autoimmune diseases such as celiac disease, type 1 diabetes mellitus, and hypo- or hyperthyroidism. Several factors have been considered as possible etiology, including genetic and epigenetic modifications and immune dysregulation. In times in which the life expectancy of people with DS has been extremely prolonged, thanks to improvements in the diagnosis and treatment of congenital heart disease and infectious complications, knowledge of the mechanisms and proper management of autoimmune diseases within this syndrome has become essential. In this short review, we aim to report the current literature regarding the genetic, immune, and environmental factors that have been proposed as the possible underlying mechanism of autoimmunity in individuals with DS, with the intent to provide insight for a comprehensive understanding of these diseases in genetic syndromes.

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Mutations of uncertain significance in heterozygous variants as a possible cause of severe short stature: a case report

Molecular and Cellular Pediatrics ◽

10.1186/s40348-020-00104-6 ◽

2020 ◽

Vol 7 (1) ◽

Author(s):

Nami Mohammadian Khonsari ◽

Sahar Mohammad Poor Nami ◽

Benyamin Hakak-Zargar ◽

Tessa Voth

Keyword(s):

Growth Hormone ◽

Short Stature ◽

Hormone Receptors ◽

Bone Growth ◽

Synergistic Effects ◽

Signs And Symptoms ◽

Bone Age ◽

Pathogenic Mutation ◽

Paracrine Factors ◽

Severe Short Stature

Abstract Background Linear bone growth is achieved by the division of chondrocytes at the growth plate and is regulated by endocrine and paracrine factors such as growth hormone. Mutations that negatively affect chondrogenesis can be a contributor to short stature. One such mutation can occur in the ACAN gene, causing short stature and advanced bone age. Similarly, mutations in growth hormone receptors (GHR) can lead to Laron syndrome (LS), one of the several disorders that are collectively called growth hormone insensitivity syndrome (GHI). Another example is Floating-Harbor syndrome (FHS), a rare autosomal dominant due to mutations in the SRCAP gene that can also result in short stature. Case presentation We report the case of a 6-year-old female with concomitant mutations in the three genes mentioned above. The mutations reported here were found on genetic studies and are usually benign, causing a variant of undetermined significance. However, our patient’s phenotype could only be explained by the compounded effects of pathogenic mutations of these genes. Some of the same mutations were also found in the patient’s father and her paternal grandfather. Both also presented with short stature, though not to the same degree as our patient. While these mutations are often reported to be insignificant, they gave rise to severe short stature and a specific phenotype in the patient when presented together. We think that even though the GHI spectrum is inherited through an autosomal recessive pattern, the sum of these heterozygous mutations resulted in severe short stature despite the limited GHI seen in our patient, the father, and the grandfather, through a rare ACAN and SRCAP mutation that, to our knowledge, has not been previously reported as a pathogenic mutation in the literature. Conclusion We investigated the possible synergistic effects of these variations on exacerbation or masking of the signs and symptoms of GHI with the hope of providing a better understanding of these genes and their function through our rare case.

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