Genetic forms of hypopituitarism and their manifestation in the neonatal period

Alatzoglou, Kyriaki S.; Dattani, Mehul

doi:10.1016/j.earlhumdev.2009.08.057

Cited by 125 publications

(86 citation statements)

References 102 publications

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“…Table 1 shows the gene defects that have been associated with GHD. Many of the proteins encoded by these genes are associated with GHD as part of combined pituitary hormone deficiency (CPHD), and function as pituitary transcription factors (for detailed information on associated clinical features and MRI appearances see (5,22,23,24)). A novel endocrine syndrome discovered by our group, immunoglobulin superfamily member 1 (IGSF1) deficiency syndrome, is primarily characterized by central hypothyroidism and macroorchidism, but can also present with hypoprolactinaemia and transient partial GHD (25,26).…”

Section: Genetic Defects Of the Gh-insulin-like Growth Factor 1 Axismentioning

confidence: 99%

MECHANISMS IN ENDOCRINOLOGY: Novel genetic causes of short stature

Wit

Oostdijk

Losekoot

et al. 2016

European Journal of Endocrinology

153

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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Section: Genetic Defects Of the Gh-insulin-like Growth Factor 1 Axismentioning

confidence: 99%

MECHANISMS IN ENDOCRINOLOGY: Novel genetic causes of short stature

Wit

Oostdijk

Losekoot

et al. 2016

European Journal of Endocrinology

153

132

View full text Add to dashboard Cite

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“…Interestingly, the posterior pituitary lobe has been consistently in a normal position in patients with mutations in transcription factors that act late, and expression is restricted to the Rathke's pouch, such as PROP1 and POU1F1 (PIT1) (Alatzoglou & Dattani 2009). …”

Section: Human Mutationsmentioning

confidence: 99%

Role of GLI2 in hypopituitarism phenotype

Arnhold¹,

França²,

Carvalho³

et al. 2015

Journal of Molecular Endocrinology

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GLI2 is a zinc-finger transcription factor involved in the Sonic Hedgehog pathway. Gli2 mutant mice have hypoplastic anterior and absent posterior pituitary glands. We reviewed the literature for patients with hypopituitarism and alterations in GLI2. Twenty-five patients (16 families) had heterozygous truncating mutations, and the phenotype frequently included GH deficiency, a small anterior pituitary lobe and an ectopic/undescended posterior pituitary lobe on magnetic resonance imaging and postaxial polydactyly. The inheritance pattern was autosomal dominant with incomplete penetrance and variable expressivity. The mutation was frequently inherited from an asymptomatic parent. Eleven patients had heterozygous non-synonymous GLI2 variants that were classified as variants of unknown significance, because they were either absent from or had a frequency lower than 0.001 in the databases. In these patients, the posterior pituitary was also ectopic, but none had polydactyly. A third group of variants found in patients with hypopituitarism were considered benign because their frequency was R0.001 in the databases. GLI2 is a large and polymorphic gene, and sequencing may identify variants whose interpretation may be difficult. Incomplete penetrance implies in the participation of other genetic and/or environmental factors. An interaction between Gli2 mutations and prenatal ethanol exposure has been demonstrated in mice dysmorphology. In conclusion, a relatively high frequency of GLI2 mutations and variants were identified in patients with congenital GH deficiency without other brain defects, and most of these patients presented with combined pituitary hormone deficiency and an ectopic posterior pituitary lobe. Future studies may clarify the relative role and frequency of GLI2 alterations in the aetiology of hypopituitarism.

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“…The most common symptoms include hypoglycemia (which may result in life-threatening seizures, apnea, or cyanosis), prolonged jaundice, or dysmorphic features on examination. 10 Dysmorphic features include midline defects, ocular and craniofacial anomalies, and microphallus in males with or without cryptorchidism. Birth size and weight are often normal or moderately reduced.…”

Section: Congenital Hypopituitarismmentioning

confidence: 99%

Necrotizing Enterocolitis in the Full-Term Infant

Chu¹,

Chiu²

2015

Pediatr Ann

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Necrotizing enterocolitis in full-term infants is relatively rare. When seen, it is usually associated with perinatal asphyxia, sepsis, or specific forms of congenital heart disease. It can also be associated with endocrinopathies. In this review, a full-term infant was found to have necrotizing enterocolitis and persistent hypoglycemia. Evaluation for hypoglycemia revealed pan-hypopituitarism, and magnetic resonance imaging confirmed this diagnosis. Timely evaluation and early initiation of hormone replacement therapy is essential to minimize long-term morbidities and mortality associated with pan-hypopituitarism. [Pediatr Ann. 2015;44(10):e237-e242.]

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Genetic forms of hypopituitarism and their manifestation in the neonatal period

Cited by 125 publications

References 102 publications

MECHANISMS IN ENDOCRINOLOGY: Novel genetic causes of short stature

MECHANISMS IN ENDOCRINOLOGY: Novel genetic causes of short stature

Role of GLI2 in hypopituitarism phenotype

Necrotizing Enterocolitis in the Full-Term Infant

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