conductive hearing loss

Baller-Gerold Syndrome

Clinical Characteristics
Ocular Features: 

The ocular features are a rather minor part of this syndrome and are found in less than a third of patients.  These primarily involve lids and adnexae with telecanthus, downslanting lid fissures, and epicanthal folds.  Some individuals have nystagmus while strabismus, blue sclerae, and ectropion have also been reported.

Systemic Features: 

The cardinal features of this syndrome are craniosynostosis and radial defects.  However, a large number of variable defects such as imperforate or anteriorly placed anus, rectovaginal fistula, absent thumbs, polydactyly, and mental retardation may also be present.  The radius may be completely absent or abnormally formed and occasionally the ulnar bone is involved as well.  Some patients have a conductive hearing loss.

Genetics

This syndrome is caused by a mutation in the RECQL4 gene at 8q24.3 and seems to be an autosomal recessive disorder.  Its syndromal status as a unique syndrome is in some doubt because of considerable phenotypic overlap with other entities such as Roberts (268300) and Saethre-Chotzen (101400) syndromes.  The latter however is caused by a mutation in the TWIST1 gene and the former by mutations in the ESCO2 gene.

The same gene is mutated in Rothmund-Thomson syndrome (268400) suggesting allelism of the two disorders.  The phenotype is vastly different in the two disorders however.

Pedigree: 
Autosomal recessive
Treatment
Treatment Options: 

No treatment is available.

References
Article Title: 

Pfeiffer Syndrome

Clinical Characteristics
Ocular Features: 

Patients may have extreme proptosis (95%) secondary to shallow orbits and exposure keratitis (41%) is a risk.  Hypertelorism, strabismus, and antimongoloid lid slants are common.  More rare signs include anterior chamber anomalies and optic nerve hypoplasia.

Systemic Features: 

Pfeiffer syndrome has been divided into 3 types, of which cases with types 2 and 3 often die young.  Type 1 has the more typical features with midface hypoplasia, broad thumbs and toes, craniosynostosis, and often some degree of syndactyly.  Adult patients with type 1 may be only mildly affected with some degree of midface hypoplasia and minor broadening of the first digits.  Hearing loss secondary to bony defects is relatively common.  Cleft palate is uncommon.  Airway malformations especially in the trachea can cause respiratory problems.

Genetics

This is a genetically heterogeneous disorder resulting from mutations in at least 2 genes, FGFR1 (8p11.2-p11.1) and FGFR2 (10q26).  The less common cases with the latter mutation are allelic to Apert (101200), Crouzon (123500), and Jackson-Weiss (123150) syndromes.  Inheritance is autosomal dominant but some cases are only mildly affected.  New mutations exhibit a paternal age effect.

Other forms of craniosynostosis in which mutations in FGFR2 have been found are: Beare-Stevenson Syndrome (123790), and Saethre-Chotzen Syndrome (101400).

Pedigree: 
Autosomal dominant
Treatment
Treatment Options: 

Exposure keratitis requires the usual treatment.  Fronto-orbital advancement surgery for the midface underdevelopment is generally helpful for the complications of proptosis.  Airway obstruction may require tracheostomy or surgical correction of the air passages.

References
Article Title: 

FGFR2 mutations in Pfeiffer syndrome

Lajeunie E, Ma HW, Bonaventure J, Munnich A, Le Merrer M, Renier D. FGFR2 mutations in Pfeiffer syndrome. Nat Genet. 1995 Feb;9(2):108.

PubMed ID: 
7719333
Subscribe to RSS - conductive hearing loss