Handbook of Genetic Counseling/CHARGE Association

CHARGE Syndrome

Introduction

Having to learn a lot in a short amount of time
Support system? The difficulty of raising three kids on your own with one having medical dependence.
Coping strategies
- Does she have a home care nurse?
- Has she used respite care, does she know about it?

Autosomal dominant, most often de novo pathogenic variants in CHD7 gene on chromosome 8
Recurrence risk for next child = 1-2%
Resources for parents: see New Parent Packet at www.chargesyndrome.org
See fact sheet below for more details that may need to be addressed

A specific set of birth defects that are found in a single child. The letters of CHARGE are no longer used for diagnosis. Diagnosis is by major and supporting features
Major features
- Coloboma in 80-90% (a cleft in the eyeball: iris, retina or disc)
- Choanal atresia in 50% - (blockage or narrowing of the passageway that connects the nose to the throat and allows a person to breathe through their nose. Extremely dangerous because newborns are obligate nose breathers until 4-6 weeks old.)
- C- cranial nerve anomalies (nearly everyone has at least one)
  - CN I - olfactory 80% (decreased or absent sense of smell)
  - CN VII - facial palsy 40% (one or both sides)
  - CN VIII - sensorineural hearing loss 90%
  - CN IX, X - swallowing difficulties (70%)
- Characteristic external ear shape
- Characteristic inner ears on MRI
  - fewer turns to the cochlea
  - small or absent semicircular canals 95%
Supporting features
- Heart defect in 70-85% (usually a VSD, PDA, Tetralogy of Fallot, or DORV - double outlet right ventricle)
- Genitourinary anomalies in 70-80% of males (small penis, hypospadias, undescended testicles)
- Kidney abnormalities
- Cleft lip
- Tracheal or esophageal abnormalities
- Post-natal short stature, sometimes with growth hormone deficiency

Feeding problems are common/swallowing difficulties
Developmental delay in 100% - because of multiple hospitalizations and sensory deficits (hearing, vision, balance)
Intellectual ability - from normal to profoundly impaired. About 50% have normal intelligence
Visual impairment
Characteristic facial features in >50% (square face, large eyes, small nostrils, small mouth, facial asymmetry with or without paralysis)
Usually there is not growth retardation prenatally. Typically babies are born with an average weight and then linear growth starts to shift below the third percentile by 6 months of age.
Typical behaviors may look similar to autism but are likely not autism

The diagnosis is clinical, based on features. All suspected children should get gene testing
The only known cause for CHARGE syndrome are pathogenic variants (mutations) in the CHD7 gene on chromosome 8. 10-20% of children with clinical diagnosis have negative (normal) CHD7 testing
Most of the time, the child with CHARGE is the first in the family to have it (de novo)

Recurrence of an affected sibling with two unaffected parents = 1-2%
An adult with CHARGE has a 50% chance of passing the gene on to each child. If a child inherits the CHD7 variant, that child may have features somewhat different from the parent.

Mortality
- There is a high mortality in children with CHARGE in the first three years - due to severe birth defects, multiple hospitalizations and surgeries. Many have severe breathing problems and/or difficulty with anesthesia
- After the first three years, children with CHARGE remain medical fragile and have higher morbidity and mortality than typical children. Even as adults, there is a higher risk of death, most likely related to breathing and swallowing issues.
Motor milestones
- Motor development will be delayed due to birth defects, surgeries, illness, low upper body tone, very poor balance (due to abnormal semicircular canals), low vision and poor hearing. Although delayed, children with CHARGE will eventually reach all milestones
Language will be delayed due to hearing loss and other issues, especially vision loss. Hearing should be tested and augmented as soon as possible. Deafblind educators (those with skills to deal with children with combined decreased vision and hearing) should be involved from early on.

If a family has one child with a known CHD7 variant, prenatal diagnosis by genetic analysis (CVS, amniocentesis) is possible
Ultrasound can evaluate for some features common in pregnancies where the fetus has CHARGE:
- Polyhydramnios
- Cardiac involvement
- Genitalia
- Kidneys
- Cleft lip/palate
- Characteristic ears by 3D ultrasound

CHARGE Syndrome Foundation, Inc: A better world for people with CHARGE syndrome. The CHARGE Syndrome Foundation champions the lifelong potential of people with CHARGE syndrome through outreach, education and research.
www.chargesyndrome.org 1-800-442-7604
- see especially New Parent Packet, For Families, and Resources

CHARGE Syndrome. Ed. Hartshorne, Hefner, Davenport, Thelin
- https://www.pluralpublishing.com/publication_cs2.htm

The information in this outline was last updated in 2017.