imperforate anus

Sweeney-Cox Syndrome

Clinical Characteristics
Ocular Features: 

 Periorbital and facial anomalies were present in the two reported patients.  Pseudoproptosis (considered secondary to deficiency of the bony orbits) accentuated by midface hypoplasia, and upper lid colobomas have been observed.  The globes were described as "small" although there were no "concerns" regarding vision in the single male patient.  Electrodiagnostic tests were "normal."    

Systemic Features: 

Multiple anomalies and malformations were present in the two reported patients, an unrelated male and female.  Severe facial dysmorphism secondary to uneven skull bone formation and suture closures is present.  The metopic ridge is prominent, the orbital bones are deficient, the occiput is flattened, the anterior fontanel and coronal sutures are wide.  Midfacial hypoplasia is present.  The neck is broad and the shoulders are narrow.  The fingers are long and the distal phalanges may be fixed in flexion.  The ears are low-set, small, and cupped.  The palate is high and may be cleft.  Cutaneous syndactyly of the fingers has been observed.  Variable developmental delays/learning difficulties are present.

The male had an imperforate anus, undescended testes and a 60 dB hearing loss.  The female had a midline cleft palate with choanal atresia requiring a tracheostomy from birth and required fundoplication and gastrostomy for gastroesophageal reflux.

Genetics

Heterozygous missense mutations in the TWIST1 gene (7p21.1) were found in both reported individuals.  These appear to have arisen de novo.

Mutations in the same gene have also been found in the Saethre-Chotzen Syndrome (101400) in which some of the same skeletal features are found.

Pedigree: 
Autosomal dominant
Treatment
Treatment Options: 

No treatment has been reported for the general condition but individual malformations may require attention.  The lid colobomas were repaired in the female but corneal exposure remained and corneal scarring and phthisis developed in the right eye.  The left eye retained some vision ("able to see large objects").

References
Article Title: 

Localized TWIST1 and TWIST2 basic domain substitutions cause four distinct human diseases that can be modeled in Caenorhabditis elegans

Kim S, Twigg SRF, Scanlon VA, Chandra A, Hansen TJ, Alsubait A, Fenwick AL, McGowan SJ, Lord H, Lester T, Sweeney E, Weber A, Cox H, Wilkie AOM, Golden A, Corsi AK. Localized TWIST1 and TWIST2 basic domain substitutions cause four distinct human diseases that can be modeled in Caenorhabditis elegans. Hum Mol Genet. 2017 Jun 1;26(11):2118-2132.

PubMed ID: 
28369379

Diagnostic value of exome and whole genome sequencing in craniosynostosis

Miller KA, Twigg SR, McGowan SJ, Phipps JM, Fenwick AL, Johnson D, Wall SA, Noons P, Rees KE, Tidey EA, Craft J, Taylor J, Taylor JC, Goos JA, Swagemakers SM, Mathijssen IM, van der Spek PJ, Lord H, Lester T, Abid N, Cilliers D, Hurst JA, Morton JE, Sweeney E, Weber A, Wilson LC, Wilkie AO. Diagnostic value of exome and whole genome sequencing in craniosynostosis. J Med Genet. 2017 Apr;54(4):260-268.

PubMed ID: 
27884935

Sweeney-Cox Syndrome

Clinical Characteristics
Ocular Features: 

Ophthalmologic examinations have not been reported.  However, periorbital and facial anomalies were present in the two reported patients.  Pseudoproptosis (considered secondary to deficiency of the bony orbits) accentuated by midface hypoplasia, and upper lid colobomas have been observed.  The globes were described as "small" although there were no "concerns" regarding vision in the single male patient.  Electrodiagnostic tests were "normal."    

Systemic Features: 

Multiple anomalies and malformations were present in the two reported patients, an unrelated male and female.  Severe facial dysmorphism secondary to uneven skull bone formation and suture closures is present.  The metopic ridge is prominent, the orbital bones are deficient, the occiput is flattened, the anterior fontanel and coronal sutures are wide.  Midfacial hypoplasia is present.  The neck is broad and the shoulders are narrow.  The fingers are long and the distal phalanges may be fixed in flexion.  The ears are low-set, small, and cupped.  The palate is high and may be cleft.  Cutaneous syndactyly of the fingers has been observed.  Variable developmental delays/learning difficulties are present.

The male had an imperforate anus, undescended testes and a 60 dB hearing loss.  The female had a midline cleft palate with choanal atresia requiring a tracheostomy from birth and required fundoplication and gastrostomy for gastroesophageal reflux.  

Genetics

Heterozygous missense mutations in the TWIST1 gene (7p21.1) were found in both reported individuals.  These appear to have arisen de novo.

Mutations in the same gene have also been found in the Saethre-Chotzen Syndrome (101400) in which some of the same skeletal features are found.

Pedigree: 
Autosomal dominant
Treatment
Treatment Options: 

No treatment has been reported for the general condition but individual malformations may require attention.  The lid colobomas were repaired in the female but corneal exposure remained and corneal scarring and phthisis developed in the right eye.  The left eye retained some vision ("able to see large objects").

References
Article Title: 

Localized TWIST1 and TWIST2 basic domain substitutions cause four distinct human diseases that can be modeled in Caenorhabditis elegans

Kim S, Twigg SRF, Scanlon VA, Chandra A, Hansen TJ, Alsubait A, Fenwick AL, McGowan SJ, Lord H, Lester T, Sweeney E, Weber A, Cox H, Wilkie AOM, Golden A, Corsi AK. Localized TWIST1 and TWIST2 basic domain substitutions cause four distinct human diseases that can be modeled in Caenorhabditis elegans. Hum Mol Genet. 2017 Jun 1;26(11):2118-2132.

PubMed ID: 
28369379

Diagnostic value of exome and whole genome sequencing in craniosynostosis

Miller KA, Twigg SR, McGowan SJ, Phipps JM, Fenwick AL, Johnson D, Wall SA, Noons P, Rees KE, Tidey EA, Craft J, Taylor J, Taylor JC, Goos JA, Swagemakers SM, Mathijssen IM, van der Spek PJ, Lord H, Lester T, Abid N, Cilliers D, Hurst JA, Morton JE, Sweeney E, Weber A, Wilson LC, Wilkie AO. Diagnostic value of exome and whole genome sequencing in craniosynostosis. J Med Genet. 2017 Apr;54(4):260-268.

PubMed ID: 
27884935

Blepharocheilodontic Syndrome 1

Clinical Characteristics
Ocular Features: 

The eyelids are disproportionately large with an associated lagophthalmos and lower lid ectropion.  The upper eyelids may have a double row of lashes (distichiasis).  Hypertelorism and a broad nasal root have been reported.

Systemic Features: 

A cleft lip and palate are major features and are usually bilateral.  The teeth are conically shaped with microdontia and oligodontia (involving both primary and secondary dentition) often present as well.  Several newborns have had an imperforate anus. Scalp hair may be sparse and hypoplastic nails have been described.  Hypothyroidism and thyroid agenesis has been documented in several patients.

Genetics

This is an autosomal dominant condition resulting from mutations in the CDH1 gene (16q22.1).

Blepharocheilodontic syndrome 2 is caused by mutations in the CTNND1 gene (16q22.1).

Other conditions with distichiasis include Blatt distichiasis (126300) and lymphedema-distichiasis (153400).

Pedigree: 
Autosomal dominant
Treatment
Treatment Options: 

Treatment consists of correction of individual anomalies such as eyelid, oral, and dental malformations.

References
Article Title: 

Blepharo-cheilo-dontic (BCD) syndrome

Gorlin RJ, Zellweger H, Curtis MW, Wiedemann HR, Warburg M, Majewski F, Gillessen-Kaesbach G, Prahl-Andersen B, Zackai E. Blepharo-cheilo-dontic (BCD) syndrome. Am J Med Genet. 1996 Oct 16;65(2):109-12.

PubMed ID: 
8911600

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: 
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