Costello syndrome

Costello syndrome is a rare multisystem disorder; only about 300 cases have been reported worldwide. It was first described in 1971, and is also known as faciocutaneoskeletal or FCS syndrome.

What are the clinical features of Costello syndrome?

Children with Costello syndrome have a distinctive facial appearance. They are short in stature. They have feeding difficulties at birth resulting in failure to thrive. There are heart defects, developmental disabilities and a tendency to grow tumours. However they tend to be happy, sociable children.

The following features may arise prior to birth.

• Polyhydraminos (excessive amniotic fluid)
• Fetus heavier than expected for gestational age, due to swelling
• Fetal distress including tachycardia (fast heart beat)
• Short limbs noted on fetal ultrasound examination

The table below describes the most common features of Costello syndrome.

Facial features	Broad mouth Big lips High forehead Deep creases
Developmental problems	Feeding problems at birth Failure to thrive Growth delay in weight and height Motor delays Sociable personality Mental retardation Delayed or disordered puberty Premature aging
Musculoskeletal system	Hypotonia (floppy muscles) Loose joints Splayed out wrists and fingers Tight Achilles tendons Kyphoscoliosis (bent-over and/or twisted spine) Osteoporosis and bony fractures in later life
Nervous system	Hydrocephalus (swelling around the brain) Seizures (20-50%)
Heart defects	These affect about 75% of children Congenital heart defects Hypertrophic cardiomyopathy (large, weak heart muscles) Abnormal rhythms
Eye signs	Ptosis (dropped eyelids) Strabismus (squint) Nystagmus (uncontrolled eye movements)
Skin signs	Loose stretchy skin Soft deep wrinkles Curly sparse hair Papillomas around the nose and elsewhere Deep creases in palms and soles Thickened or darkened skin Thick toenails
Tumours	Benign and malignant tumours starting in childhood Rhabdomyosarcoma, neuroblastoma, bladder tumours are most frequent

Costello syndrome

What causes Costello syndrome?

Costello syndrome is due to a genetic defect that is inherited in autosomal dominant manner. However, almost all cases described have resulted from new mutations in the HRAS gene, as individuals with Costello syndrome are unlikely to have children.

The HRAS gene provides instructions for making the H-Ras protein, which helps control cell growth and division. Mutation causes a permanently active HRAS protein which directs cells to grow and divide constantly. This leads to the growth of benign and malignant tumours.

How is Costello syndrome diagnosed?

Costello syndrome is mainly a clinical diagnosis, but may be confirmed by specialist laboratories that can test for specific mutations in HRAS gene.

What is the treatment for Costello syndrome?

Treatment may be required for specific disorders, such as:

• Tube feeding in infancy
• Physiotherapy for musculoskeletal problems
• Surgery for heart defects and tumours
• Cryotherapy of facial papillomas

As the children grow older, it is important to screen for benign and malignant tumours so they can be treated at an early stage. The following procedures may be done at intervals:

• Echocardiograms
• Abdominal and pelvic ultrasound
• Urine analysis for blood

There is no cure for the condition.

Draft 24 May 2008