Key to a few congenital syndromes

Achondroplasia A skeletal dysplasia caused by mutations in fibroblast growth

factor receptor 3 (FGFR3) gene. Autosomal dominant inheritance but most cases
are new mutations so recurrence risk is small. Can be diagnosed at birth from
clinical features including short limbs, large head with a broad and prominent
forehead, short, tapered and splayed fingers, exaggerated lumbar lordosis. Risk
of spinal cord compression/hydrocephalus

Alport Syndrome – a genetic condition characterized by end-stage kidney

disease, hearing loss and eye abnormalities (although there do no usually affect
sight). People with Alport syndrome experience progressive renal failure.
Haematuria is universal; proteinuria is a feature as renal disease progresses.

Angelman Syndrome – ‘Happy Puppet Syndrome’ – a rare congenital disorder

characterized by learning difficulties, epilepsy and jerky movements and ataxia,
liked with mutation on chromosome 15

Cockayne syndrome – Rare. Characterised by short stature and premature

ageing. Features include a failure to gain weight and grow at the expected rate,
microcephaly, impaired development of the nervous system, photosensitivity

Crouzon Syndrome – a craniosynostosis syndrome, characterized by premature

closure of the coronal sutures and facially by mid-face hypoplasia, proptosis
secondary to shallow orbits, mild hypertelorism, beak-shaped nose and a small
jaw. Intelligence is usually normal

Down’s syndrome (Trisomy 21) – a genetic condition that typically causes some
level of learning disability and characteristic (dysmorphic) physical features.
Many babies born with Down’s syndrome are diagnosed after birth and are likely
to have:
 Hypotonia
 Mongolian slanted eyes
 Small mouth with protruding tongue
 Flat occiput
 Below average weight and length at birth

Duchenne Muscular dystrophy – a rare X-linked recessive form of muscular

dystrophy affecting boys which results in muscle degeneration and death. The
disorder is caused by a mutation in the dystrophin gene, located on the X
chromosome. (Becker MD is very similar to Duchenne MD but the symptoms are
milder as these patients still have partially functioning dystrophin.)

Fragile X syndrome - Fragile X syndrome is a genetic condition which causes a

range of developmental problems including cognitive impairment/learning
difficulty. It is caused by mutations in the FMR1 gene (an unstable trinucleotide
repeat sequence). If affects males; their mothers are assumed to be carriers.
Physical features become more prominent with ageing – long face, big ears,
prominent jaw, normal-large head size. Frequency 1 in 2000-3000 live births

Goldenhar syndrome – Oculo-Auriculo-Vertebral syndrome – a rare congenital

defect characterized by incomplete development of the ear, nose, soft palate and
mandible. Cervical vertebral and cardiac abnormalities are common. Usually
sporadic.

Jervell-Lange-Nielsen syndrome – a type of long QT syndrome associated with

severe bilateral sensorineural hearing loss. Long OT syndrome predisposes to
cardiac arrhythmias which may lead to fainting, seizures or sudden death.

Klinefelter syndrome - syndrome characterised by XXY karyotype (47XXY)

Mild learning difficulties, small testes, gynaecomastia. Males tend to be tall and
have female distribution of body fat. Facial hair growth is sparse and body hair
scanty. Males are usually sterile

Klippel-Feil syndrome – a bone disorder characterized by congenital fusion of

two or more cervical vertebrae. Three major features result from this: a short
neck, the resulting appearance of a low hairline at the back of the neck, a limited
range of neck movement.

Landau Kleffner syndrome –also called acquired epileptic aphasia. It is an age-

related epeiepsy syndrome of childhood. Its main features are a loss of speech
and language skills with seizures.. The speech and language skills may improve
with time. It usually starts before the age of 6 years and affects twice as many
boys as girls.

Marfan syndrome - a genetic connective tissue disorder. Thos affected have

long limbs arachnoidactyly, flexible joints and scoliosis, pectus excavatum, mitral
or aortic valve problems with dilatation of the aortic root. They also have
subluxation of the lens of the eye upwards and outwards.

Medium Chain Acyl Co-A Deficiency (MCAD) - - a condition in which the body
is unable to break down certain fats and convert them to energy, particularly
during periods of fasting

Mucopolysaccharidoses (MPS)– a group of metabolic disorders caused by the

absence or malfunctioning of lysosomal enzymes needed to break down
molecules called glycosaminoglycans (GAGS). These are found in each of our cells
that help build bone, cartilage, tendons, corneas, skin and connective tissue. They
are also found in joint fluid. People with MPS either produce insufficient of one of
the 11 enzymes necessary to break down the GAGS, or produce enzymes that do
not work properly. GAGS collect in the cells, blood and connective tissue over
time, leading to permanent progressive cellular damage which affects
appearance, physical abilities, organ and system functioning and mental
development.
Congenital Myotonic dystrophy - the early childhood form of myotonic
dystrophy with symptoms evident from birth. The condition usually occurs
when the mother has myotonic dystrophy and passes it on to her child in a more
severe form. Inheritance is autosomal dominant. Babies may have breathing
problems at birth and are very floppy. They may lack facial expression because
they cannot make the usual range of facial movements. Upper lip is shaped like
an inverted V. Motor and cognitive development tend to be delayed and speech
may be unclear. Talipes occurs commonly. Myotonia - the impaired relaxtion of a
muscle develops with age.

Neurofibromatosis Type I (NF-1)– is caused by a mutation of a gene on

chromosome 17 that is responsible for cell division. NF-1 causes tumours
(neurofibromata) akongthe nervous system and can grow anywhere on the body.
Common symptoms of NF-1 include café-au-lait patches, axillary freckling, Lisch
nodules in the eye, skin neurofibromata, larger plexiform neurofibromata,
pseudarthroses.

Neuronal Migration Disorder – a heterogeneous group of disorders that, it is

supposed, share the same aetio-pathological mechanism: a variable degree of
disruption in the migration of neuroblasts during the development of the CNS in
fetal life.

Phenylketonuria (PKU) – an inborn error of metabolism caused by absent, or

virtually absent, phenylalanine hydroxylase enzyme activity, resulting in
impaired metabolism of phenylalanine. Early diagnosis and strict dietary
treatment prevents long-term sequelae; untreated PKU can lead to learning
disability, seizures and poor growth. It may also result in a musty smell and
lighter skin.

Pendred syndrome – a genetic disorder leading to congenital bilateral

sensorineural hearing loss and goiter with euthyroid or mild hypothyroidism.

Rett syndrome – a genetic post-natal disorder of the grey matter of the brain
almost exclusively affecting females associated with mutation of MECP2 gene
commonly. Clinical features include small hands and feet, microcephaly,
repetitive stereotyped hand movements e.g wringing, seizures, gastrointestinal
disturbance, severe learning disability. They typically have no verbal skills and
50% of affected individuals do not walk.

Soto syndrome – genetic disorder characterized by a distinctive facial

appearance, overgrowth in childhood, learning disabilities or delayed
development of mental and motor abilities. Facial features include long, narrow
face, high forehead, flushed cheeks, small pointed chin.

Treacher-Collins syndrome – this syndrome affects the development of bones

and other tissues of the face. Typical features include downward slanting eyes,
micrognathia, conductive hearing loss, under-developed zygoma, drooping part
of lateral lower eyelids and malformed or absent ears.
Tuberous Sclerosis – a rare multisystem genetic disease that causes benign
tumours to grow in the brain and in other vital organs such as kidneys, heart,
eyes, lungs and skin. Symptoms may include seizures, learning disability,
developmental delay, behavioural problems. It is caused by a mutation in either
of two genes, TSC1 an TSC2 which code for hamartin and tuberin respectively.

Turner Syndrome - Genetic syndrome with XO karyotype (45XO). Affects girls.

Short stature, short webbed neck, shield-shaped chest, wide spaced nipples,
pedal oedema, a congenital heart defect (mostly coarctation) and streak ovaries.
Variable learning difficulties.

Urea cycle disorders – genetic disorders which are caused by the deficiency of
one of the enzymes in the urea cycle which is responsible for removing ammonia
from the blood stream.

Usher syndrome – the most common condition that affects both hearing and
vision. The major symptoms are sensorineural deafness and retinitis
pigmentosa. Balance problems may also be present.

Velo-cardio-facial syndrome (22q 11 deletion) – the most common

microdeletion syndrome. It is caused by the deletion of a small piece of
chromosome 22 near the middle of the chromosome. The features of this
syndrome vary widely. Common signs and symptoms are congenital heart
disease, cleft palate, distinctive facial features, developmental delay. The immune
system may also be compromised.

Williams syndrome: a rare neurodevelopmental disorder characterized by a

distinctive elfin facial appearance, along with a low nasal bridge, a cheerful
demeanour and ease with strangers, cardiovascular disease, developmental
delay.