Severe Hajdu‐Cheney syndrome with upper airway obstruction

Abstract

Hajdu-Cheney syndrome is an autosomal dominant disorder of acroosteolysis, skull deformities, characteristic facial abnormalities, osteoporosis, joint laxity, early loss of teeth, hearing loss, and a hoarse voice. We report on an 8 1/2-year-old boy with Hajdu-Cheney syndrome and cystic kidney disease, congenital heart disease, hydrocephalus, cleft lip and palate, hydrosyringomyelia, club feet, splenomegaly, hypospadias, vertebral anomalies, and upper airway obstruction. A review of 44 patients did not uncover any other patients with all of these manifestations, nor any patient with upper airway obstruction. Hajdu-Cheney syndrome appears to encompass a broader phenotype than previously recognized. The documentation of these additional anomalies is valuable because the findings of acroosteolysis and osteoporosis can present later in the course.

The developmental biology of genetic Notch disorders

“…Impaired Jag1 and Notch2 signaling also results in ventricular septation defects, aortic arch patterning defects and pulmonary artery stenosis, all of which are conditions present in individuals with Alagille syndrome (Manderfield et al, 2012;Varadkar et al, 2008). Another explanation for the congenital heart disease found in Hajdu-Cheney patients (Crifasi et al, 1997) is provided by the role of Notch2 in the formation of trabecular myocardium: under physiological conditions, Notch2 activity must be suppressed by Numb and Numbl to balance the formation of compact versus trabecular myocardium, and its overabundance causes hypertrabeculation, non-compactation and septation defects (Yang et al, 2012). Further studies are required to explain how Notch2 achieves these roles, when the developing myocardium is devoid of Notch2 mRNA expression (D'Amato et al, 2016b).…”