Cataracts, Growth Hormone Deficiency, and Skeletal Dysplasia

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

This is likely an autosomal recessive disorder resulting from homozygous or compound heterozygous mutations in the IARS2 gene (1q41).

Treatment
Treatment Options: 

Appropriate hormonal replacement therapy can be beneficial.  Individual skeletal surgery for scoliosis and hip dislocation should be considered.  Visually significant lens opacities may require surgery.

References
Article Title: 

Mutation in The Nuclear-Encoded Mitochondrial Isoleucyl-tRNA Synthetase IARS2 in Patients with Cataracts, Growth Hormone Deficiency with Short Stature, Partial Sensorineural Deafness, and Peripheral Neuropathy or with Leigh Syndrome

Schwartzentruber J, Buhas D, Majewski J, Sasarman F, Papillon-Cavanagh S, Thiffaut I, Sheldon KM, Massicotte C, Patry L, Simon M, Zare AS, McKernan KJ; FORGE Canada Consortium, Michaud J, Boles RG, Deal CL, Desilets V, Shoubridge EA, Samuels ME. Mutation in The Nuclear-Encoded Mitochondrial Isoleucyl-tRNA Synthetase IARS2 in Patients with Cataracts, Growth Hormone Deficiency with Short Stature, Partial Sensorineural Deafness, and Peripheral Neuropathy or with Leigh Syndrome. Hum Mutat. 2014 Nov;35(11):1285-9.

PubMed ID: 
25130867

References

Schwartzentruber J, Buhas D, Majewski J, Sasarman F, Papillon-Cavanagh S, Thiffaut I, Sheldon KM, Massicotte C, Patry L, Simon M, Zare AS, McKernan KJ; FORGE Canada Consortium, Michaud J, Boles RG, Deal CL, Desilets V, Shoubridge EA, Samuels ME. Mutation in The Nuclear-Encoded Mitochondrial Isoleucyl-tRNA Synthetase IARS2 in Patients with Cataracts, Growth Hormone Deficiency with Short Stature, Partial Sensorineural Deafness, and Peripheral Neuropathy or with Leigh Syndrome. Hum Mutat. 2014 Nov;35(11):1285-9.

PubMedID: 25130867

Liberfarb RM, Jackson AH, Eavey RD, Robb RM. Unique hereditary sensory and autonomic neuropathy with growth hormone deficiency. J Child Neurol. 1993 Jul;8(3):271-6.

PubMedID: 8409271