NDH syndrome is a rare disorder that has so far been reported in less than 20 individuals worldwide. It is characterized by intrauterine growth retardation, non-immune neonatal diabetes mellitus, congenital hypothyroidism and mild facial dysmorphism. Symptoms usually manifest in the first few weeks of life. Facial anomalies include a long philtrum, low set ears, epicanthal folds, a flat nasal bridge and a thin upper lip. Depending on the severity of the disorder, symptoms may also include polycystic kidneys, congenital glaucoma, hepatic fibrosis, osteopenia and sensorineural deafness.
Treatment of the disorder is based on stabilizing glucose and thyroid hormone levels by administering insulin and oral levothyroxine respectively. While severe forms of the disorder have led to the death of some patients in early childhood, patients with milder phenotypes have survived into adulthood.
Senee et al. (2006) studied two consanguineous families from Saudi Arabia with individuals affected by NDH syndrome. The first family had three affected individuals with neonatal diabetes, intrauterine growth retardation, congenital hypothyroidism and facial dysmorphism. The patients also presented with congenital glaucoma, polycystic kidneys and hepatic fibrosis. All three patients died in early childhood. The second family had one affected child who showed similar symptoms but did not have any liver or kidney manifestations. The syndrome was mapped to chromosome 9p using linkage analysis. Further investigations revealed a homozygous 426 kb deletion in the GLIS3 gene in the affected individual from the second family and a homozygous insertion 2067insC in the same gene in the affected individual from the first family.