colobomas

Temtamy Syndrome

Clinical Characteristics
Ocular Features: 

Bilateral chorioretinal colobomas may be present and involve the optic nerve in one-third of patients.  Visual acuity is not measureable but significant vision impairment is evident in most patients and may be progressive in some individuals.  Several have been reported with dislocated lenses, ptosis, microcornea, cataracts, microphthalmia, myopia, and posterior staphylomas.

Systemic Features: 

Mild, nonspecific craniofacial dysmorphism is often present.  Some form of macrocephaly, with an elongated face, low-set ears, and micrognathia has been reported.  Short stature is of the proportionate type.  Significant developmental delay is evident during childhood and patients are nonverbal. A variety of cardiovascular anomalies such as septal defects, aortic dilation, and patent ductus arteriosus have been described. MRI shows mild hypoplasia of the corpus callosum.   The gait may be ataxic and some (59%) individuals have spasticity of limb muscles with or without contractures.  Seizures develop in early childhood, usually before the age of 3 years, and are difficult to control. 

Genetics

The inconsistent and highly variable phenotype hints that this is a genetically heterogeneous condition.  Many patients seem to have an autosomal recessive condition secondary to mutations in C12orf57 (12p13.31).

A syndrome consisting primarily of colobomas, ptosis, hypertelorism, and global delay (243310) has some similar clinical features but is caused by mutations in ACTG1.

Treatment
Treatment Options: 

No therapy is available for the syndrome but attempts to control the seizures should be made. 

References
Article Title: 

Exome sequencing identifies compound heterozygous mutations in C12orf57 in two siblings with severe intellectual disability, hypoplasia of the corpus callosum, chorioretinal coloboma, and intractable seizures

Platzer K, Huning I, Obieglo C, Schwarzmayr T, Gabriel R, Strom TM, Gillessen-Kaesbach G, Kaiser FJ. Exome sequencing identifies compound heterozygous mutations in C12orf57 in two siblings with severe intellectual disability, hypoplasia of the corpus callosum, chorioretinal coloboma, and intractable seizures. Am J Med Genet A. 2014 May 5. [Epub ahead of print].

PubMed ID: 
24798461

Whole-exome sequencing identifies mutated c12orf57 in recessive corpus callosum hypoplasia

Akizu N, Shembesh NM, Ben-Omran T, Bastaki L, Al-Tawari A, Zaki MS, Koul R, Spencer E, Rosti RO, Scott E, Nickerson E, Gabriel S, da Gente G, Li J, Deardorff MA, Conlin LK, Horton MA, Zackai EH, Sherr EH, Gleeson JG. Whole-exome sequencing identifies mutated c12orf57 in recessive corpus callosum hypoplasia. Am J Hum Genet. 2013 Mar 7;92(3):392-400.

PubMed ID: 
23453666

New autosomal recessive multiple congenital abnormalities/mental retardation syndrome with craniofacial dysmorphism absent corpus callosum, iris colobomas and connective tissue dysplasia

Temtamy SA, Salam MA, Aboul-Ezz EH, Hussein HA, Helmy SA, Shalash BA. New autosomal recessive multiple congenital abnormalities/mental retardation syndrome with craniofacial dysmorphism absent corpus callosum, iris colobomas and connective tissue dysplasia. Clin Dysmorphol. 1996 Jul;5(3):231-40. Review.

PubMed ID: 
8818452

Duane-Radial Ray Syndrome

Clinical Characteristics
Ocular Features: 

Most individuals have features of Duane’s anomaly, sometimes unilaterally.  Optic pallor with poor vision has been described in well-studied patients who also had thinning of the retinal nerve fiber layer.  The optic disk may appear hypoplastic.  Visual evoked potentials and pattern ERG amplitudes are decreased.

Other less common ocular features are microcornea, microphthalmia, ophthalmoplegia, hypertelorism, cataracts, epicanthal folds, colobomas, and chorioretinal scars.

Systemic Features: 

The systemic features are inconsistent (variable expressivity) with most patients having some variation of hypodactyly, polydactyly, syndactyly, and malformation of the hands.  The thumb is the most common digit involved and this is often associated with thenar hypoplasia.  Other skeletal features of the radial ray syndrome including absence of the radial and ulnar bones are variably present.  Hearing loss is described as sensorineural in etiology but malformations of the pinnae and external meatus are sometimes present.

Kidney anomalies include horseshoe malformations, abnormal rotation, ectopia, small size, vesicoureteric reflux, and pelvicalyceal dilatation.

Genetics

This is an autosomal dominant disorder due to heterozygous mutations in the SALL4 gene (20q13.2).

This syndrome is sometimes confused with the Holt-Oram syndrome but the latter is the result of mutations in a different gene and lacks ocular and renal abnormalities.  Duane syndrome 1 and 2 may also occur as isolated conditions.

The considerable clinical heterogeneity has led to alternate titles for this syndrome. For example, what is sometimes called the IVIC syndrome (147750) with similar features is also caused by mutations in this gene.  Duane-radial ray syndrome has also been called Okihiro syndrome. 

 

Pedigree: 
Autosomal dominant
Treatment
Treatment Options: 

Treatment is symptomatic in most cases although reconstructive surgery may be helpful for severe hand deformities.  Low vision aids may be beneficial.  

References
Article Title: 
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