# 15 - X linked recessive disorders

# X-linked recessive disorders

© SPMM Course 
X-linked recessive disorders 
If a recessive disease-causing mutation occurs on the single X chromosome of a man, this is sufficient to 
cause disease, as another X chromosome is not existent to compensate any deficiencies. As females have 
two copies of the X chromosome, they need a double identical mutation for disease expression, which is 
extremely rare. But during random X inactivation if most X chromosomes carrying normal alleles are 
inactivated (called unfavourable Lyonisation), then these females can manifest the disease phenotype –
termed as manifesting heterozygotes. But nevertheless the severity of expressed disease is mild and can 
go unnoticed too. Skipped generations are commonly seen because an affected male can transmit the 
disease-causing mutation to a heterozygous daughter, who remains normal phenotypically but carries and 
transmits the disease-causing allele to her sons. 
From McGuffin et al. (ed) Psychiatric genetics and genomics. Oxford Press: 2002 
Male-to-male transmission is not seen in X-linked inheritance. Affected male mates with a homozygous 
normal female, all of the daughters will be heterozygous carriers; all of the sons will be homozygous 
normal. If a carrier female mates with normal male (which is often the case in this transmission), then half 
Disorder 
Location and mode of transmission 
Features 
Tuberous sclerosis 
 
9q34 / 16p13 
 
Auto.dominant (but most are 
spontaneous) 
 
1 in 30 000 
Adenoma sebaceum, normal to sever MR, 
ash leaf macules, brain hamartomas, heart 
and kidney cysts 
Treacher Collins 
syndrome 
 
5q31 
 
Auto.dominant 
 
1 in 40 000 
Maxilla-mandibular hypoplasia, malformed 
pinna, down slanting palpebrae, mild to 
moderate MR 
Apert syndrome 
 
10q 
 
Auto dominant 
Variable MR, cranio synostosis, shallow 
orbits, trapezoid mouth, ‘mitten’ hands and 
feet. 
Noonan syndrome 
 
Chr 12 
 
Auto.dominant 
 
1 in 1 500 
Mild MR, short stature, nuchal 
edema/webbed neck, pulmonary stenosis, 
cryptorchidism 
Hurler syndrome 
 
4p16 
 
Auto. recessive 
 
1 in 100 000 
Deteriorating IQ after age 2, coarse facies, 
clouded cornea, joint stiffness. 
Lesch-Nyhan syndrome 
 
Xq 26-27 
 
X linked recessive 
 
Deficiency of the enzyme 
hypoxanthine-guanine 
phosphoribosyltransferase (HGPRT) 
Poor muscle control, and moderate mental 
retardation – year 1. Self-mutilating 
behaviors, characterized by lip and finger 
biting – by year 2. Hyperuricemia and 
hyperuricosuria -severe gout and kidney 
problems – can present anytime.