OMIM ID:
Short-Rib Thoracic Dysplasia 9
Alternate Names
Defective Genes
Clinical Characteristics
Ocular Features
A pigmentary retinopathy resembling retinitis pigmentosa is present in the majority of individuals. Reduced acuity is likely responsible for the associated nystagmus and occasional strabismus. Night blindness is a feature although the age of onset is unknown. Visual acuity is decreased in the first decade but at least one patient at age 40 years still had vision of 20/40-20/50. The ERG shows decreased scotopic and photopic responses as early as 12 years of age. The retinopathy has been described as an atypical nonpigmented retinal degeneration in the peripheral retina. However, bone-spicule pigmentary deposits have been noted. The retinal disease is progressive.
Systemic Features
The LFT140 mutation has widespread effects, impacting the kidney, liver and skeletal systems. The thorax is shortened, while the ribs are abnormally short and may result in respiratory difficulties, recurrent infections, and an early demise. The middle phalanges of the hands and feet often have cone-shaped epiphyses, especially notable in childhood and leading to brachydactyly. The long bones are often shortened as well. The femoral neck can be short while the femoral epiphyses are often flattened. Microcephaly has been reported in several individuals.
The liver may be enlarged and become fibrotic. The kidneys often are cystic and histologically may have sclerosing glomerulonephropathy. Kidney disease has an onset in the first decade and its progression often defines the survival prognosis. Renal transplantation can be lifesaving when nephronophthisis develops. Psychomotor delays have been reported but are uncommon.
Genetics
Inheritance
Homozygous or compound heterozygous mutations in the IFT140 gene (16p13.3) have been identified. However, there is some genetic heterogeneity since several patients having the typical phenotype have been reported with only heterozygous mutations.
This may be the same condition as Retinitis Pigmentosa 80 (617781) in which the same mutation occurs.
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.