Growth Abnormalities Resulting in Short Stature in Genetic Syndromes

Background and Objectives: Diagnostic delay is common in attenuated Mucopolysaccharidosis Type I (MPS Ia) due to the rarity of the disease and the variability of clinical presentation. Short stature and impaired growth velocity are frequent findings in MPS Ia, but they rarely raise suspicion as paediatric endocrinologists are generally poorly trained to detect earlier and milder clinical signs of this condition. Materials and Methods: Following a consensus-based methodology, a multidisciplinary panel including paediatric endocrinologists, paediatricians with expertise in metabolic disorders, radiologists, and rheumatologists shared their experience on a possible clinical approach to the diagnosis of MPS Ia in children with short stature or stunted growth. Results: The result was the formation of an algorithm that illustrates how to raise the suspicion of MPS Ia in a patient older than 5 years with short stature and suggestive clinical signs. Conclusion: The proposed algorithm may represent a useful tool to improve the awareness of paediatric endocrinologists and reduce the diagnostic delay for patients with MPS Ia.

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Short stature in genetic syndromes: Selected issues

Advances in Clinical and Experimental Medicine ◽

10.17219/acem/67051 ◽

2018 ◽

Vol 27 (3) ◽

pp. 409-414 ◽

Cited By ~ 3

Author(s):

Izabela Laczmanska ◽

Justyna Kuliczkowska-Plaksej ◽

Agnieszka Stembalska

Keyword(s):

Short Stature ◽

Genetic Syndromes

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Endocrinology

General Pediatrics Board Review ◽

10.1093/med/9780190848712.003.0012 ◽

2020 ◽

pp. 249-267

Author(s):

Gina Capodanno ◽

Shylaja Srinivasan ◽

Christine T. Ferrara-Cook

Keyword(s):

Short Stature ◽

Delayed Puberty ◽

Genetic Syndromes ◽

Endocrine Disorder ◽

Abnormal Growth ◽

Endocrine Hormone ◽

Question And Answer ◽

Answer Format

Disruptions of growth and puberty are typically the first signs of an endocrine disorder. Using vignettes and a question-and-answer format, this chapter discusses common and uncommon cases of hormone dysfunction presenting from infancy through adolescence. Topics in the chapter include short stature, delayed puberty, obesity, diabetes, hypoglycemia, conditions of endocrine hormone deficiencies and excess and associated genetic syndromes. Challenges in distinguishing normal versus abnormal growth are also reviewed.

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Do you know this syndrome?

Anais Brasileiros de Dermatologia ◽

10.1590/abd1806-4841.20131934 ◽

2013 ◽

Vol 88 (4) ◽

pp. 664-666 ◽

Cited By ~ 3

Author(s):

Rogerio Nabor Kondo ◽

Ligia Márcia Mario Martins ◽

Vivian Cristina Holanda Lopes ◽

Rodrigo Antonio Bittar ◽

Fernanda Mendes Araújo

Keyword(s):

Differential Diagnosis ◽

Short Stature ◽

Noonan Syndrome ◽

Congenital Heart ◽

Heart Defects ◽

Facial Dysmorphism ◽

Genetic Syndromes ◽

Cardiac Defects ◽

Important Differential Diagnosis ◽

Dental Malocclusion

Noonan Syndrome is one of the most common genetic syndromes and also an important differential diagnosis in children presenting with syndromic facies similar to Turner's syndrome phenotype. This syndrome is characterized by facial dysmorphism, congenital heart defects, short stature and also a wide phenotypic variation. This article discusses the case of a 10 year-old patient with Noonan syndrome that presented typical facies, cardiac defects (pulmonary dilatation and mitral regurgitation), dental malocclusion, micrognatism, short stature and a certain degree of learning disability.

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Endocrine and Growth Abnormalities in 4H Leukodystrophy Caused by Variants in POLR3A, POLR3B, and POLR1C

The Journal of Clinical Endocrinology & Metabolism ◽

10.1210/clinem/dgaa700 ◽

2020 ◽

Cited By ~ 2

Author(s):

Félixe Pelletier ◽

Stefanie Perrier ◽

Ferdy K Cayami ◽

Amytice Mirchi ◽

Stephan Saikali ◽

...

Keyword(s):

Short Stature ◽

Hypogonadotropic Hypogonadism ◽

Autosomal Recessive Disorder ◽

Cross Sectional Study ◽

Delayed Puberty ◽

Cross Sectional ◽

Pathogenic Variants ◽

Neurological Features ◽

A Prospective Study ◽

Growth Abnormalities

Abstract Context 4H or POLR3-related leukodystrophy is an autosomal recessive disorder typically characterized by hypomyelination, hypodontia, and hypogonadotropic hypogonadism, caused by biallelic pathogenic variants in POLR3A, POLR3B, POLR1C, and POLR3K. The endocrine and growth abnormalities associated with this disorder have not been thoroughly investigated to date. Objective To systematically characterize endocrine abnormalities of patients with 4H leukodystrophy. Design An international cross-sectional study was performed on 150 patients with genetically confirmed 4H leukodystrophy between 2015 and 2016. Endocrine and growth abnormalities were evaluated, and neurological and other non-neurological features were reviewed. Potential genotype/phenotype associations were also investigated. Setting This was a multicenter retrospective study using information collected from 3 predominant centers. Patients A total of 150 patients with 4H leukodystrophy and pathogenic variants in POLR3A, POLR3B, or POLR1C were included. Main Outcome Measures Variables used to evaluate endocrine and growth abnormalities included pubertal history, hormone levels (estradiol, testosterone, stimulated LH and FSH, stimulated GH, IGF-I, prolactin, ACTH, cortisol, TSH, and T4), and height and head circumference charts. Results The most common endocrine abnormalities were delayed puberty (57/74; 77% overall, 64% in males, 89% in females) and short stature (57/93; 61%), when evaluated according to physician assessment. Abnormal thyroid function was reported in 22% (13/59) of patients. Conclusions Our results confirm pubertal abnormalities and short stature are the most common endocrine features seen in 4H leukodystrophy. However, we noted that endocrine abnormalities are typically underinvestigated in this patient population. A prospective study is required to formulate evidence-based recommendations for management of the endocrine manifestations of this disorder.

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

BMJ Case Reports ◽

10.1136/bcr-2019-231737 ◽

2020 ◽

Vol 13 (2) ◽

pp. e231737 ◽

Cited By ~ 1

Author(s):

Jaime Guevara-Aguirre ◽

Carolina Guevara ◽

Alexandra Guevara ◽

Antonio AWD Gavilanes

Keyword(s):

Developing Countries ◽

Mental Retardation ◽

Medical Care ◽

Short Stature ◽

South American ◽

Genetic Syndromes ◽

Laron Syndrome ◽

South American Country ◽

Genetic Syndrome ◽

Severe Short Stature

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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Y chromosome aberration in a patient with cloacal-bladder exstrophy-epispadias complex: an unusual finding

Arquivos Brasileiros de Endocrinologia & Metabologia ◽

10.1590/s0004-27302013000200009 ◽

2013 ◽

Vol 57 (2) ◽

pp. 148-152

Author(s):

Mirian Yumie Nishi ◽

Thais Cotrim Martins ◽

Elaine Maria Frade Costa ◽

Berenice Bilharinho Mendonca ◽

Amilcar Martins Giron ◽

...

Keyword(s):

Short Stature ◽

Y Chromosome ◽

Chromosome Aberration ◽

Bladder Exstrophy ◽

Genetic Syndromes ◽

Secondary Sexual Characteristics ◽

Brazilian Patient ◽

Sexual Characteristics ◽

Urogenital Malformation ◽

Secondary Sexual

Chromosome aberrations or genetic syndromes associated with cloacal-bladder exstrophy complex have rarely been reported. The aim of this report is to describe a 14 year-old female Brazilian patient with a complex urogenital malformation, short stature, lack of secondary sexual characteristics and Y chromosome aberration. A girl with cloacal bladder exstrophy complex was referred for evaluation of short stature and absence of secondary sexual characteristics. Pre-pubertal levels of gonadotropins and sex steroids were observed at the beginning of monitoring, but follow-up showed a progressive increase in testosterone levels. The patient underwent gonadectomy and testicular tissue was identified without dysgenetic characteristics. She had a 46,X,inv(Y)(p11.1q11.2) karyotype, normal SRY sequence, and no Y deletions. The pericentric inversion of Y chromosome apparently did not contribute to the development of the complex urogenital malformation in this patient. Currently, no teratogenic agent, environmental factor, or defective genes have been recognized as etiologic factors for this type of urogenital malformation.

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A novel de novo partial xq duplication in a girl with short stature, nonverbal learning disability and diminished ovarian reserve - effect of growth hormone treatment and fertility preservation strategies: a case report and up-to-date review

International Journal of Pediatric Endocrinology ◽

10.1186/s13633-019-0071-z ◽

2020 ◽

Vol 2020 (1) ◽

Author(s):

Francesca Parissone ◽

Mairi Pucci ◽

Emanuela Meneghelli ◽

Orsetta Zuffardi ◽

Rossana Di Paola ◽

...

Keyword(s):

Learning Disability ◽

Short Stature ◽

Fertility Preservation ◽

Ovarian Reserve ◽

De Novo ◽

Diminished Ovarian Reserve ◽

Nonverbal Learning Disability ◽

Genetic Syndromes ◽

Severe Scoliosis ◽

Nonverbal Learning

Abstract Background Xq duplication is a rare condition with a very variable phenotype, which could mimic other genetic syndromes involving the long arm of chromosome X. Sometimes short stature and diminished ovarian reserve (DOR) may be present. Treatments with rGH (Recombinant growth Hormon) or with fertility preservation strategies have not been previously described. Case presentation We present the case of a female with a novel de novo Xq partial duplication (karyotype: 46,Xder(X)(qter→q21.31::pter→qter) confirmed by array-CGH analysis. She presented with short stature, Nonverbal Learning Disability, developmental delay during childhood, severe scoliosis, spontaneous onset of menarche and irregular menstrual cycles. AMH (Anti-Müllerian Hormone) allowed detection of a preserved but severely diminished ovarian reserve with a POI (Premature Ovarian insufficiency) onset risk. She was effectively subjected to fertility preservation strategies and rGH therapy. We also reviewed other published cases with Xq duplication, reporting the main clinics characteristics and any adopted treatment. Conclusions rGH treatment and cryopreservation in a multidisciplinary approach are good therapeutic strategies for Xq duplication syndrome with short stature and premature ovarian failure.

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