short philtrum

Basel-Vanagaite-Smirin-Yosef Syndrome

Clinical Characteristics
Ocular Features: 

The eyes appear abnormally far apart.  Ptosis, microcornea, congenital cataracts, sparse eyebrows, and strabismus are usually present.  Epicanthal folds are often seen.

Systemic Features: 

Psychomotor development is severely delayed and with delay or absence of milestones.  DTRs are often hyperactive but some infants are described as hypotonic.  Some individuals have seizures.  There may be a nevus flammeus simplex lesion on the forehead and body hair is sparse.  Cleft palate, cardiac septal defects, hypospadius, thin corpus callosum and cerebral ventricular dilation have been observed.  The upper lip may have a tented morphology with everted lower lip vermilion. A short philtrum is common. 

Genetics

A homozygous missense mutation in the MED25 gene (19q13.33) has been reported and the transmission pattern is consistent with autosomal recessive inheritance.

Pedigree: 
Autosomal recessive
Treatment
Treatment Options: 

No known treatment has been reported.

References
Article Title: 

Homozygous MED25 mutation implicated in eye-intellectual disability syndrome

Basel-Vanagaite L, Smirin-Yosef P, Essakow JL, Tzur S, Lagovsky I, Maya I, Pasmanik-Chor M, Yeheskel A, Konen O, Orenstein N, Weisz Hubshman M, Drasinover V, Magal N, Peretz Amit G, Zalzstein Y, Zeharia A, Shohat M, Straussberg R, Monte D, Salmon-Divon M, Behar DM. Homozygous MED25 mutation implicated in eye-intellectual disability syndrome. Hum Genet. 2015 Jun;134(6):577-87.

PubMed ID: 
25792360

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
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