Alström syndrome is associated with short stature and reduced <scp>GH</scp> reserve

Romanò, Sara; Maffei, Pietro; Bettini, V; Milan, Gabriella; Favaretto, Francesca; Gardiman, Marina Paola; Marshall, Jan D.; Greggio, Nella Augusta; Pozzan, Giovanni Battista; Collin, Gayle B.; Naggert, Jürgen Κ.; Bronson, Roderick T.; Vettor, Roberto

doi:10.1111/cen.12180

Cited by 23 publications

(20 citation statements)

References 37 publications

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“…Hypothyroidism (range 11–36%) and sub-clinical hypothyroidism have been reported in patients with ALMS [ 19 , 25 , 44 , 45 ]. Hypothyroidism may be primary or secondary and it is related to autoimmunity in 20% of cases [ 45 ].…”

Section: Clinical Presentationmentioning

confidence: 99%

Consensus clinical management guidelines for Alström syndrome

Tahani

Maffei

Dollfus

et al. 2020

Orphanet J Rare Dis

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Alström Syndrome (ALMS) is an ultra-rare multisystem genetic disorder caused by autosomal recessive variants in the ALMS1 gene, which is located on chromosome 2p13. ALMS is a multisystem, progressive disease characterised by visual disturbance, hearing impairment, cardiomyopathy, childhood obesity, extreme insulin resistance, accelerated non-alcoholic fatty liver disease (NAFLD), renal dysfunction, respiratory disease, endocrine and urologic disorders. Clinical symptoms first appear in infancy with great variability in age of onset and severity. ALMS has an estimated incidence of 1 case per 1,000,000 live births and ethnically or geographically isolated populations have a higher-than-average frequency. The rarity and complexity of the syndrome and the lack of expertise can lead to delayed diagnosis, misdiagnosis and inadequate care. Multidisciplinary and multiprofessional teams of experts are essential for the management of patients with ALMS, as early diagnosis and intervention can slow the progression of multi-organ dysfunctions and improve patient quality of life. These guidelines are intended to define standard of care for patients suspected or diagnosed with ALMS of any age. All information contained in this document has originated from a systematic review of the literature and the experiences of the authors in their care of patients with ALMS. The Appraisal of Guidelines for Research & Evaluation (AGREE II) system was adopted for the development of the guidelines and for defining the related levels of evidence and strengths of recommendations. These guidelines are addressed to: a) specialist centres, other hospital-based medical teams and staffs involved with the care of ALMS patients, b) family physicians and other primary caregivers and c) patients and their families.

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Section: Clinical Presentationmentioning

confidence: 99%

Consensus clinical management guidelines for Alström syndrome

Tahani

Maffei

Dollfus

et al. 2020

Orphanet J Rare Dis

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“…Compound heterozygosity for a gene encoding a protein important for ciliary function (IFT172) can cause functional GHD, pituitary hypoplasia, and ectopic posterior pituitary (34), and also Alström syndrome, caused by a mutation of ALMS1 encoding a protein localized to the centrosomes and basal bodies of ciliated cells (35) is associated with GHD. GHD has also been documented in a congenital malformation syndrome associated with a paternal deletion of 6q24.2-q25.2 (36), complete generalized glucocorticoid resistance (37), and mitochondrial diseases (38).…”

Section: Gh Deficiencymentioning

confidence: 99%

MECHANISMS IN ENDOCRINOLOGY: Novel genetic causes of short stature

Wit

Oostdijk

Losekoot

et al. 2016

European Journal of Endocrinology

154

132

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The fast technological development, particularly single nucleotide polymorphism array, array-comparative genomic hybridization, and whole exome sequencing, has led to the discovery of many novel genetic causes of growth failure. In this review we discuss a selection of these, according to a diagnostic classification centred on the epiphyseal growth plate. We successively discuss disorders in hormone signalling, paracrine factors, matrix molecules, intracellular pathways, and fundamental cellular processes, followed by chromosomal aberrations including copy number variants (CNVs) and imprinting disorders associated with short stature. Many novel causes of GH deficiency (GHD) as part of combined pituitary hormone deficiency have been uncovered. The most frequent genetic causes of isolated GHD are GH1 and GHRHR defects, but several novel causes have recently been found, such as GHSR, RNPC3, and IFT172 mutations. Besides well-defined causes of GH insensitivity (GHR, STAT5B, IGFALS, IGF1 defects), disorders of NFkB signalling, STAT3 and IGF2 have recently been discovered. Heterozygous IGF1R defects are a relatively frequent cause of prenatal and postnatal growth retardation. TRHA mutations cause a syndromic form of short stature with elevated T 3 /T 4 ratio. Disorders of signalling of various paracrine factors (FGFs, BMPs, WNTs, PTHrP/IHH, and CNP/NPR2) or genetic defects affecting cartilage extracellular matrix usually cause disproportionate short stature. Heterozygous NPR2 or SHOX defects may be found in w3% of short children, and also rasopathies (e.g., Noonan syndrome) can be found in children without clear syndromic appearance. Numerous other syndromes associated with short stature are caused by genetic defects in fundamental cellular processes, chromosomal abnormalities, CNVs, and imprinting disorders.

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“…With respect to pituitary gland function in AS, GH functional deficiency has been observed in 50% of AS patients [9]; similarly hypogonadism [10] has been detected in half of male patients, suggesting the presence of a hypothalamic-pituitary-gonadic axis dysfunction. GH/sex hormone and pituitary gland abnormalities could represent the two sides (morphological and functional) of this axis dysfunction.…”

Section: Discussionmentioning

confidence: 99%