Growth without growth hormone and similar dysmorphic features in three patients with sporadic combined pituitary hormone deficiencies.
OBJECTIVE
Mutations in the HESX1 gene are associated with a broad spectrum of phenotypes: septo-optic dysplasia, midline defects, pituitary abnormalities with consequent hypopituitarism, isolated growth hormone (GH) deficiency or combined pituitary hormone deficiencies (CPHD). This study examined the prevalence of mutations in the HESX1 gene in patients with CPHD.


METHODS
Sixty patients with sporadic CPHD without septo-optic dysplasia were screened for mutations in HESX1.


RESULTS
Three patients were found to be heterozygous for the same Asn125Ser variant in the HESX1 gene. In all 3, panhypopituitarism was presented in the neonatal period, manifested by severe hypoglycemia and neonatal jaundice in 2 patients and respiratory distress in 1. Remarkable findings from physical examination included coarse face; prominent, large, low-set ears; and skeletal abnormalities. Magnetic resonance imaging, performed in 2 patients, revealed a hypoplastic anterior and ectopic posterior pituitary without other midline anomalies. Despite persistent GH deficiency and undetectable levels of insulin-like growth factor 1, all patients had normal linear growth along the 10-25th percentile without GH therapy.


CONCLUSIONS
The present study expands the clinical picture of HESX1 mutations by demonstrating that patients heterozygous for Asn125Ser may have a severe endocrinologic and neuroradiologic phenotype and similar dysmorphic features appearing very early in life.
The Jesse Z and Sara Lea Shafer Institute for Endocrinology and Diabetes, National Center for Childhood Diabetes, Schneider Children's Medical Center of Israel, and Felsenstein Medical Research Center, IL-49202 Petach Tikva, Israel.
G
G
Gat-Yablonski
L
L
Lazar
M
M
Bar
L
L
de Vries
N
N
Weintrob
M
M
Phillip
D000293:Adolescent; D004252:DNA Mutational Analysis; D005146:Facial Asymmetry / Q000150:complications* / Q000235:genetics; D006128:Growth / Q000502:physiology*; D006130:Growth Disorders / Q000150:complications* / Q000235:genetics; D018398:Homeodomain Proteins / Q000235:genetics; D019382:Human Growth Hormone / Q000172:deficiency; D006801:Humans; D008297:Male; D008875:Middle Aged; D010900:Pituitary Diseases / Q000150:complications* / Q000235:genetics / Q000503:physiopathology; D010907:Pituitary Hormones / Q000172:deficiency*
C489736:HESX1 protein, human; D018398:Homeodomain Proteins; D010907:Pituitary Hormones; D019382:Human Growth Hormone