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8. What are SHOX insufficiency-related disorders?

SHOX insufficiency-related disorders include Turner syndrome, Leri–Weil dys-

chondrosteosis, and Langer mesomelic dysplasia. The differences among these

disorders are summarized in the table given below.

Characteristics Turner syndrome

Leri–Weil

dyschondrosteosis

Langer mesomelic

dysplasia

SHOX gene

defect

Haploinsufficiency Haploinsufficiency Homozygous deficiency

Gender Only females Both sexes Both sexes

Mean height

SDS

−3.2 SDS −2.4 SDS −6.2 SDS

Skeletal

defects

Mesomelia ± Mesomelia + Mesomelia +++

Cubitus valgus Cubitus valgus Hypoplasia/aplasia of

ulna, fibula, and

mandible

Short 4th and 5th

metacarpals

Short 4th and 5th

metacarpals

Madelung deformity

(8 %)

Madelung deformity

(75 %)

High arched palate High arched palate

Gonadal

failure

Ye s No No

Cardiac and

renal

anomalies

Ye s No No

In addition, SHOX haploinsufficiency has also been described in individuals

with idiopathic short stature.

9. What is Lyon’s hypothesis?

Lyon’s hypothesis states that one of the X chromosomes in somatic cells of a

normal female embryo undergoes inactivation during 16–64 cell stage (second

week of life). This inactivation occurs in a random fashion and may involve X

chromosome derived from either parent. This silencing of X chromosome in a

female is a compensatory response to achieve equality in genetic dose between

a male and female, as X chromosome consists of >1,000 genes as compared to

Y chromosome with barely 200 genes. This silencing of second X chromosome

is mediated by the gene XIST.

8 Turner Syndrome