Del(X)(p)

 

Epidemiology and Etiology:

·         Pseudoautosomal dominant inheritance

·         See Turner syndrome variants

 

Common sites:

·          

 

Gross features:

·         Short stature homeobox (SHOX) gene (Xp22.3 and Yp11.3)

·         SHOX-related haploinsufficiency disorders

·         Leri-Weill dyschondrosteosis (LWD)

·         Severe end of the spectrum

·         Short stature

·         Mesomelia

·         Middle portion of a limb is shortened in relation to a proximal portion

·         Madelung deformity

·         Abnormal alignment of the radius, ulna, and carpal bones at the wrist

·         Develops in mid-to-late childhood

·         More common and severe in females

·         70% of patients with this syndrome have SHOX deletions or mutations

·         SHOX-related short stature (mild end of the spectrum)

·         Homozygous deletion or compound heterozygous mutations resulting in nullizygosity:

·         Langer-type of mesomelic dwarfism

·         Severe short stature (final height ~130cm)

·         Limb abnormalities:

·         Shortening of long-bones

·         More marked in proximal segment

·         Aplasia or severe hypoplasia of ulna and fibula

·         Thickened and curved radius and tibia

·         NOT Madelung deformity typically

·         Mild hypoplasia of the mandible

·         Xp22.3 deletions involving more than SHOX:

·         Contiguous gene deletion syndrome:

·         Ichthyosis (STS and flanking sequences) (Xp22.3)

·         Kallman syndrome (KAL1) (Xp22.3)

·         Chondrodysplasia punctata (ARSE)

·         Skeletal deformities

·         Short stature

·         Mental retardation (MRX)

·         Ocular albinism (OA1)

·         Turner

 

Histologic features:

·          

 

Immunophenotype:

Marker:

Sensitivity:

Specificity:

 

 

 

 

Molecular features:

·         SHOX deletions:

·         Usually not visible on G-banded karyotype

 

Other features:

·         See figure on p. 203 of Gardner

·         Amenorrhea

·         Infertility

·         Xp22.3 deletions involving more than SHOX:

·         Contiguous gene deletion syndrome:

·         Ichthyosis

·         Learning/behavioural difficulties

·         Kallman syndrome (KAL1) (KS)

·         Chondrodysplasia punctata

·         Skeletal deformities

·         Short stature

 

References:

·         Gardner RJM, Sutherland GR. Chromosome Abnormalities and Genetic Counseling. 2nd ed. Oxford University Press, USA; 1996.

·         Gardner RJM, Sutherland GR. Chromosome abnormalities and genetic counseling. Oxford University Press; 2004.

·         Kallmann Syndrome -- GeneReviews -- NCBI Bookshelf. Available at: http://www.ncbi.nlm.nih.gov/bookshelf/br.fcgi?book=gene&part=kms [Accessed June 13, 2009].