Fragile X syndrome - Most common cause of inherited learning disability

FXS is the most common known cause of autism or 'autistic-like' behaviours.

Symptoms also can include characteristic physical and behavioural features and
delays in speech and language development.

Childhood syndromes:

Patau syndrome (trisomy 13):

Microcephalic, small eyes
Cleft lip/palate
Polydactyly
Scalp lesions

Edward's syndrome (trisomy 18):

Micrognathia
Low-set ears
Rocker bottom feet
Overlapping of fingers

Fragile X:
Learning difficulties
Macrocephaly
Long face
Large ears
Macro-orchidism

Noonan syndrome:
Webbed neck
Pectus excavatum
Short stature
Pulmonary stenosis

Pierre-Robin syndrome:
Micrognathia
Posterior displacement of the tongue (may result in upper airway obstruction)
Cleft palate

Prader-Willi syndrome:
Hypotonia
Hypogonadism
Obesity

William's syndrome:
Short stature
Learning difficulties
Friendly, extrovert personality
Transient neonatal hypercalcaemia
Supravalvular aortic stenosis

Cri du chat syndrome (chromosoome 5p deletion syndrome):

Characteristic cry (hence the name) due to larynx and neurological problems
Feeding difficulties and poor weight gain
Learning difficulties
Microcephaly and micrognathism
Hypertelorism
Autosomal Recessive:
In autosomal recessive inheritance
only homozygotes are affected
males and females are equally likely to be affected
not manifest in every generation - may 'skip a generation'

If two heterozygote parents

25% chance of having an affected (homozygote) child
50% chance of having a carrier (heterozygote) child
25% chance of having an unaffected (i.e. genotypical) child

If one affected parent (i.e. homozygote for gene) and one unaffected (i.e. not a
carrier or affected)
all the children will be carriers

Autosomal recessive disorders are often metabolic in nature and are generally more
life-threatening compared to autosomal dominant conditions

Caput succedaneum
Present at birth
Typically forms over the vertexx and crosses suture lines
Resolves within days

Cephalohematoma:
Typically develops several hours after birth
Most commonly in parietal region, doesn't cross suture lines
May take several months to resolve

Common features:
Swelling over head of new born
More common following prolonged, difficult deliveries
Managed conservatively

A cephalohaematoma is seen as a swelling on the newborns head. It typically

develops several hours after delivery and is due to bleeding between the periosteum
and skull. The most common site affected is the parietal region

Jaundice may develop as a complication.

A cephalohaematoma up to 3 months to resolve.

Trinucleotide repeat disorders

Trinucleotide repeat disorders are genetic conditions caused by an abnormal number

of repeats (expansions) of a repetitive sequence of three nucleotides. These
expansions are unstable and may enlarge which may lead to an earlier age of onset
in successive generations - a phenomenon known as anticipation*. In most cases, an
increase in the severity of symptoms is also noted

Examples - note dominance of neurological disorders

Fragile X (CGG)
Huntington's (CAG)
myotonic dystrophy (CTG)
Friedreich's ataxia* (GAA)
spinocerebellar ataxia
spinobulbar muscular atrophy
dentatorubral pallidoluysian atrophy

*Friedreich's ataxia is unusual in not demonstrating anticipation

Down's syndrome: Epidemiology and genetics:

Risk increases with maternal age:

Age:

20 - 1 in 1500
30 - 1 in 800
35 - 1 in 270
40 - 1 in 100
45- 1 in 50 or greater

One way to remember - start with 1/100 at 30 years, and then dividing the
denominator by 3 for every 5 years extra of age

Cytogenetics:

Non disjunction - 94% of cases - risk of recurrence 1/100 if mother <35 y

Robertsonian translocation (usually onto 14) - 5% - 10-15% if mother is
translocation carrier / 2.5 % if father is translocation carrier
Mosaicism - 1%

The chance of a further child with Down's syndrome is approx 1 in 100 if the mother
is less than 35 y old. If trisomy 21 is a result of a translocation hence the risk
is much higher

Undescended testis

Undescended testis occurs in around 2-3% of term male infants, but is much more
common if the baby is preterm. Around 25% of cases are bilateral.

Complications of undescended testis

infertility
torsion
testicular cancer
psychological

Management
Unilateral undescended testis
NICE CKS now recommend referral should be considered from around 3 months of age,
with the baby ideally seeing a urological surgeon before 6 months of age
Orchidopexy: Surgical practices vary although the majority of procedures are
performed at around 1 year of age
Bilateral undescended testes
Should be reviewed by a senior paediatrician within 24hours as the child may need
urgent endocrine or genetic investigation

Unilateral undescended testicle - review at 3 months - if persistent then refer

Congenital infections:

CMV - most common congenital infection in the UK

Maternal infection is usually asymptomatic

Rubella:

features:
Sensorineural deafness
Congenital cataracts
CHD (PDA, Glaucoma)

Other:
Growth retardation
Hepatosplenomegaly
Purpuric skin lesions
Salt and pepper chorioretinitis
Microphthalmia
Cerebral plasy

Toxoplasmosis:

Feat:
Cerebral calcification
Chorioretinitis
Hydrocephalus

Other:
Anaemia
Hepatosplenomegaly
Cerebral Palsy

Cytomegalovirus:
Feat:
Low birth weight
Purpuric skin lesions
Sensorineural deafness
Microcephaly

Other:
Visual impairment
Learning disability
Encephalitis / seizures
Pneumonitis
H-S-megaly
Anaemia
Jaundice
Cerebral Palsy