prominent nose

Rubinstein-Taybi Syndrome 2

Clinical Characteristics
Ocular Features: 

Highly-arched and bushy eyebrows are often seen.  The lashes are long and bushy and lid fissures tend to slope downward.

The ocular phenotype has not been fully described no doubt due to the rarity of cases.  Individuals with type 1 (RSTS1) have been described with congenital glaucoma, nystagmus, corneal abnormalities of shape (such as keratoglobus, sclerocornea, megalocornea), pigmentary retinopathy, and VEP evidence of rod and cone dysfunction have been described.

Systemic Features: 

The phenotype of RSTS2 is more variable than the somewhat similar RSTS1.  Less than 10% of individuals with Rubinstein-Taybi syndrome have type 2 while over 50% have type 1.  The facial dysmorphism nay be less severe in RSTS2.

Mild to moderate intellectual disability with psychosocial problems such as autism is nearly universal.  Microcephaly, a broad nasal bridge, a beaked nose, high-arched palate and some degree of micrognathia are characteristic.  The lower lip often appears 'pouty' and protrudes beyond the upper lip while the hard palate is highly arched.  Pregnancy may be complicated by pre-eclampsia and growth restriction.  Swallowing and feeding issues are common.  Syndactyly is often present and there is considerable variability in the size of the toes and thumbs.  Some patients with RSTS2 do not have evidence of the classic broad thumbs and toes characteristic of RSTS1.

Genetics

Heterozygous mutations in EP300 (22q13.2) have been found in this condition.  Virtually all cases occur de novo.  Rubinstein-Taybi Syndrome 1 (180849) is a phenotypically similar disorder resulting from a different mutation (CREBBP).

Pedigree: 
Autosomal dominant
Treatment
Treatment Options: 

There is no treatment for this condition.

References
Article Title: 

Oculootofacial Dysplasia

Clinical Characteristics
Ocular Features: 

Many patients have lower lid colobomas, sometimes with malformations of the zygoma.  The palpebral fissures may appear narrow while some patients have a suggestion of hypertelorism.

Systemic Features: 

Neural development is normal but patients have significant facial dysmorphism. A variety of organ and bony malformations have been described.  Cardiac septal defects and sometimes renal malformations may be present.  The ears are large and are sometimes associated with preauricular tags.  Cleft lip and/or palate with bifid uvula, micrognathia, high nasal bridge, large nose, a short philtrum, choanal atresia, and mixed hearing loss are often present.  Choanal atresia is common.

Genetics

Biallelic loss-of-function mutations in the TXNL4A gene have been found in this presumed autosomal recessive condition. 

Pedigree: 
Autosomal recessive
Treatment
Treatment Options: 

Individual malformations can often be surgically corrected.

References
Article Title: 

Compound heterozygosity of low-frequency promoter deletions and rare loss-of-function mutations in TXNL4A causes Burn-McKeown syndrome

Wieczorek D, Newman WG, Wieland T, Berulava T, Kaffe M, Falkenstein D, Beetz C, Graf E, Schwarzmayr T, Douzgou S, Clayton-Smith J, Daly SB, Williams SG, Bhaskar SS, Urquhart JE, Anderson B, O'Sullivan J, Boute O, Gundlach J, Czeschik JC, van Essen AJ, Hazan F, Park S, Hing A, Kuechler A, Lohmann DR, Ludwig KU, Mangold E, Steenpass L, Zeschnigk M, Lemke JR, Lourenco CM, Hehr U, Prott EC, Waldenberger M, Bohmer AC, Horsthemke B, O'Keefe RT, Meitinger T, Burn J, Ludecke HJ, Strom TM. Compound heterozygosity of low-frequency promoter deletions and rare loss-of-function mutations in TXNL4A causes Burn-McKeown syndrome. Am J Hum Genet. 2014 Dec 4;95(6):698-707.

PubMed ID: 
25434003
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