cognitive deficits

Roberts Syndrome

Clinical Characteristics
Ocular Features: 

The eyes often appear prominent as the result of shallow orbits.  Hypertelorism and microphthalmia can be present.  The sclerae can have a bluish hue.   Cataracts and central corneal clouding plus scleralization and vascularization of the peripheral corneas are sometimes seen.  Lid colobomas and down-slanting palpebral fissures may be present.

Systemic Features: 

Failure of both membranous and long bones to grow properly lead to a variety of abnormalities such as craniosynostosis, hypomelia, syndactyly, oligodactyly, malar hypoplasia, short neck, micrognathia, and cleft lip and palate.  The long bones of the limbs may be underdeveloped or even absent.  Contractures of elbow, knee, and ankle joints are common as are digital anomalies.  Low birth weight and slow postnatal growth rates are usually result in short stature.  The hair is often sparse and light-colored. 

Mental development is impaired and some children are diagnosed to have mental retardation.  Cardiac defects are common.  Facial hemangiomas are often present as are septal defects and sometimes a patent ductus arteriosus.  External genitalia in both sexes appear enlarged.  The kidneys may be polycystic or horseshoe-shaped.

Genetics

This is an autosomal recessive condition caused by mutations in the ESCO2 gene (8p21.1).  Mutations in the same gene are also responsible for what some have called the SC phocomelia syndrome (269000) which has a similar but less severe phenotype.  Some consider the two disorders to be variants of the same condition and they are considered to be the same entity in this database.  The gene product is required for structural maintenance of centromeric cohesion during the cell cycle.  Microscopic anomalies of the centromeric region (puffing of the heterochromatic regions) are sometimes seen during cell division.

The Baller-Gerold syndrome (218600) has some phenotypic overlap with Roberts syndrome but is caused by mutations in a different gene (RECQL4).

Pedigree: 
Autosomal recessive
Treatment
Treatment Options: 

Severely affected infants may be stillborn or die in infancy.  Other individuals live to adulthood.  There is no treatment for this condition beyond specific correction of individual anomalies.

References
Article Title: 

Watson Syndrome

Clinical Characteristics
Ocular Features: 

Iris nodules similar to those seen in neurofibromatosis are found in some but not all patients with Watson syndrome.

Systemic Features: 

Short stature and low normal intelligence are the most consistent features.  Pulmonic stenosis and cafe-au-lait spots are also common.   The macrocephaly is relative and not striking.  Neurofibromas have been seen in a minority of patients.

Genetics

Mutations in the NF1(17q11.2) gene have been identified in members of several large pedigrees with an apparent autosomal dominant pattern.

It remains uncertain if this condition is allelic to neurofibromatosis I(162200) or if Watson syndrome is the result of mutations in contiguous genes.

The LEOPARD syndrome(151100) shares some clinical similarities such as short stature, pulmonic stenosis, cognitive deficits and cafe-au-lait spots but is caused by mutations in PTPN11.   The phenotype also resembles Noonan syndrome in some aspects.

Pedigree: 
Autosomal dominant
Treatment
Treatment Options: 

There is no known treatment for this condition but multidisciplinary management is recommended for isolated problems.

References
Article Title: 

Watson syndrome: is it a subtype of type 1 neurofibromatosis

Allanson JE, Upadhyaya M, Watson GH, Partington M, MacKenzie A, Lahey D, MacLeod H, Sarfarazi M, Broadhead W, Harper PS, et al. Watson syndrome: is it a subtype of type 1 neurofibromatosis? J Med Genet. 1991 Nov;28(11):752-6.

PubMed ID: 
1770531

Fraser Syndrome 1

Clinical Characteristics
Ocular Features: 

Cryptophthalmos is the major ocular malformation in Fraser syndrome but is a feature in only 93% of patients.  The globe is often small and sometimes completely absent or in some cases consisting of only rudimentary ocular tissue.  The cornea is often adherent to the eyelid tissue.  The lacrimal ducts may be deformed or absent and the lids are often fused.

Systemic Features: 

The most common malformations seen in this disorder are syndactyly (61.5%), cryptophthalmos (88%), and genitourinary malformations but others of a great variety have also been reported, such as laryngeal stenosis, deafness, and deformities of the nares and external auditory meati.  Ambiguous genitalia occur in 17%.   Some infants are stillborn and many do not survive the neonatal period.  Cognitive deficits and congenital heart disease are common.

Genetics

Fraser syndrome 1 is caused by homozygous or heterozygous mutations in the FRAS1 gene (4q21.21).

Fraser syndrome 2 (617666) results from homozygous mutations in the FREM2 gene (13q13.3).  Parental consanguinity is common (25%) and familial patterns are consistent with autosomal recessive inheritance.

Fraser syndrome 3 (617667) results from homozygous mutations in the GRIP1 gene (12q14.3).  Three consanguineous families have been reported.  

Mutations in GRIP1 (PAD14) (12q14.3) have also been found in 3 families in which the parents were consanguineous.

Isolated cryptophthalmos  (123570) also occurs in autosomal dominant pedigrees as well as sporadically.  It is rarely found as an incidental feature of other syndromes.

Pedigree: 
Autosomal recessive
Treatment
Treatment Options: 

No treatment is available.

References
Article Title: 

Pages

Subscribe to RSS - cognitive deficits