flattened femoral epiphyses

Short-Rib Thoracic Dysplasia 9

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. 


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. 

Autosomal recessive
Treatment Options: 

There is no treatment for the general disease.  Renal and pulmonary function needs to be monitored with intervention as needed.  Some patients have benefitted from renal transplantation.

Article Title: 

Combined NGS approaches identify mutations in the intraflagellar transport gene IFT140 in skeletal ciliopathies with early progressive kidney Disease

Schmidts M, Frank V, Eisenberger T, Al Turki S, Bizet AA, Antony D, Rix S, Decker C, Bachmann N, Bald M, Vinke T, Toenshoff B, Di Donato N, Neuhann T, Hartley JL, Maher ER, Bogdanovic R, Peco-Antic A, Mache C, Hurles ME, Joksic I, Guc-Scekic M, Dobricic J, Brankovic-Magic M, Bolz HJ, Pazour GJ, Beales PL, Scambler PJ, Saunier S, Mitchison HM, Bergmann C. Combined NGS approaches identify mutations in the intraflagellar transport gene IFT140 in skeletal ciliopathies with early progressive kidney Disease. Hum Mutat. 2013 May;34(5):714-24.

PubMed ID: 

Mainzer-Saldino syndrome is a ciliopathy caused by IFT140 mutations

Perrault I, Saunier S, Hanein S, Filhol E, Bizet AA, Collins F, Salih MA, Gerber S, Delphin N, Bigot K, Orssaud C, Silva E, Baudouin V, Oud MM, Shannon N, Le Merrer M, Roche O, Pietrement C, Goumid J, Baumann C, Bole-Feysot C, Nitschke P, Zahrate M, Beales P, Arts HH, Munnich A, Kaplan J, Antignac C, Cormier-Daire V, Rozet JM. Mainzer-Saldino syndrome is a ciliopathy caused by IFT140 mutations. Am J Hum Genet. 2012 May 4;90(5):864-70.

PubMed ID: 
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