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.   

NDH syndrome is found to follow an autosomal recessive pattern of inheritance.  This disorder has been linked to mutations in the GLIS3 gene which encodes a transcription factor of the Kruppel-like zinc finger protein family.  GLIS3 is predicted to play a key role in cellular regulation of development and is associated with pancreatic endocrine development, beta-cell maintenance, and insulin regulation.  The most common GLIS3 mutations are partial gene deletions resulting in the absence of tissue-specific transcripts of the gene.  Other mutations include homozygous insertions that result in a frameshift and a truncated protein or transversions that result in amino acid substitutions at highly conserved residues of the protein.