OMIM ID:
Cataracts, Growth Hormone Deficiency, and Skeletal Dysplasia
Alternate Names
Defective Genes
Clinical Characteristics
Ocular Features
Lens opacities can be seen in infancy or childhood and may be congenital in onset. Nystagmus has been noted in one patient.
Systemic Features
There is considerable clinical heterogeneity in the phenotype. Motor milestones may be slightly delayed. Dysmorphic features in at least some individuals include bushy eyebrows, a prominent forehead, and a small mouth. Thoracic scoliosis and genu valgum may be present. Physical growth is reduced during infancy and childhood resulting in a short stature in adulthood. Growth hormone and cortisol deficiency have been documented. Episodic hypoglycemia has been documented. The pituitary adenohypophysis appears atrophied on MRI.
Neurosensory hearing loss has been diagnosed in the first two years of life. A distal sensory neuropathy with loss of pain, temperature and touch sensation may be present late in the first decade of life. There are no cognitive deficits and patients can live independently.
Genetics
Inheritance
This is likely an autosomal recessive disorder resulting from homozygous or compound heterozygous mutations in the IARS2 gene (1q41).
Pedigree
Autosomal recessive
In order for autosomal recessive disorders to be expressed, offspring generally must inherit two mutations, one from each carrier parent. Carriers with only one mutation, such as the parents, do not have clinical disease. Note that carrier parents can expect that 1 in 4 children (25%) will inherit both mutations and have the disorder, 2 in 4 children (50%) will be carriers like their parents, while 1 in 4 children (25%) inherit neither mutation.
In order for autosomal recessive disorders to be expressed, offspring generally must inherit two mutations, one from each carrier parent. Carriers with only one mutation, such as the parents, do not have clinical disease. Note that carrier parents can expect that 1 in 4 children (25%) will inherit both mutations and have the disorder, 2 in 4 children (50%) will be carriers like their parents, while 1 in 4 children (25%) inherit neither mutation.