Growth hormone deficiency with advanced bone age: phenotypic interaction between GHRH receptor and CYP21A2 mutations diagnosed by sanger and whole exome sequencing

SUMMARY Isolated growth hormone deficiency (IGHD) is the most common pituitary hormone deficiency and, clinically, patients have delayed bone age. High sequence similarity between CYP21A2 gene and CYP21A1P pseudogene poses difficulties for exome sequencing interpretation. A 7.5 year-old boy born to second-degree cousins presented with severe short stature (height SDS −3.7) and bone age of 6 years. Clonidine and combined pituitary stimulation tests revealed GH deficiency. Pituitary MRI was normal. The patient was successfully treated with rGH. Surprisingly, at 10.8 years, his bone age had advanced to 13 years, but physical exam, LH and testosterone levels remained prepubertal. An ACTH stimulation test disclosed a non-classic congenital adrenal hyperplasia due to 21-hydroxylase deficiency explaining the bone age advancement and, therefore, treatment with cortisone acetate was added. The genetic diagnosis of a homozygous mutation in GHRHR (p.Leu144His), a homozygous CYP21A2 mutation (p.Val282Leu) and CYP21A1P pseudogene duplication was established by Sanger sequencing, MLPA and whole-exome sequencing. We report the unusual clinical presentation of a patient born to consanguineous parents with two recessive endocrine diseases: non-classic congenital adrenal hyperplasia modifying the classical GH deficiency phenotype. We used a method of paired read mapping aided by neighbouring mis-matches to overcome the challenges of exome-sequencing in the presence of a pseudogene.

Congenital hypopituitarism: Monitoring after coronary artery bypass grafting.

Cardiovascular disease in patients with congenital hypopituitarism is not rare; however, there is a lack of reports referring to cardiac interventions in such patients. We present a 76-year-old man with complete pituitary hormone deficiency, who presented with recurrent events of unstable angina. He had a significant stenosis of the left anterior descending artery and he underwent off-pump coronary artery bypass. Our aim is to present the successful management of this patient with congenital hypopituitarism who underwent cardiac surgery and to review the relevant literature.

Basal encephalocele associated with morning glory syndrome: case report

The basal encephaloceles refer to rare entities and they correspond to herniation of brain tissue through defects of skull along the cribiform plate or the sphenoid bone. A rare morning glory syndrome, with characteristic retinal defect has been reported in association with basal encephaloceles. Hypophysis hormonal deficiencies may occur. We accounted for a pituitary dwarfism with delayed diagnosed transsphenoidal encephalocele associated with morning glory syndrome, showing the alterations found in retinography, computed tomography and magnetic resonance imaging.

As encefaloceles basais são entidades raras e correspondem a herniações do tecido cerebral através de um defeito do crânio, ao longo da lâmina crivosa etmoidal ou do osso esfenoidal. A rara síndrome morning glory, com alterações de fundo de olho características pode apresentar-se associada à encefalocele basal. Deficiências hormonais hipofisárias podem ocorrer. Relatamos caso de nanismo hipofisário com encefalocele transesfenoidal de diagnóstico tardio associada à síndrome de morning glory, mostrando as alterações na retinografia, tomografia computadorizada e ressonância magnética.

Gingival fibromatosis and growth hormone deficiency syndrome--report of a rare case and review of literature.

Oikarinen et al in 1989 reported a syndrome associated with generalized gingival fibromatosis and growth hormone deficiency. This is a case report of a 15-year-old female patient who presented to the Government Dental College, Chennai with generalized gingival fibromatosis and growth hormone deficiency. Interestingly, the histopathology of the excised gingival overgrowth showed dense collagenous connective tissue in which were strewn calcified structures that resembled cementum. This syndrome is being reported for the second time after its first case report in 1989 by Oikarinen et al. We are herewith reporting this case for its rarity with a brief review of literature of syndromes associated with generalized gingival fibromatosis.