Examples, inheritance patterns, and clinical descriptions of several types of life-threatening inherited conditions. The listed categories overlap considerably but are a useful framework for thinking about inherited conditions.

Condition type and examples	Inheritance	Description and clinical course
*Metabolic Disease*
MELAS	Mitochondrial	Characterized by mitochondrial encephalomyopathy, lactic acidosis, and strokelike episodes that typically present in mid- to late childhood. Early development is often normal. Seizures and hearing loss are common.
Maple syrup urine disease (MSUD)	Autosomal recessive	Caused by branched-chain alpha-ketoacid dehydrogenase complex deficiency that, without treatment, results in poor feeding, irritability, coma, and central respiratory failure. Manifestations vary with level of enzyme activity.
*Multiple Malformations*
Smith-Lemli-Opitz syndrome	Autosomal recessive	Individuals may have multiple anomalies of cleft palate, heart defect, hypospadias, abnormal genitalia, growth retardation. The condition results from mutations in the gene encoding 7-dehydrocholesterol reductase, an enzyme involved in cholesterol metabolism.
Noonan syndrome	Autosomal dominant	Individuals may have congenital heart disease, coagulation abnormalities, cryptorchidism, chest deformities, and developmental delay. There are several genes known to cause the condition; however, a genetic change is not detected in all individuals with a clinical diagnosis.
*Chromosomal*
Trisomy 13	Chromosomal	Often presents prenatally or at birth with multiple anomalies, including congenital heart disease and craniofacial malformations. Infants usually die in the first year of life from central apnea, but the clinical course is variable.
Williams syndrome	Chromosomal	Individuals often have cardiovascular disease, endocrine abnormalities, connective tissue differences, and mild mental retardation. A contiguous chromosomal deletion involving 7q11.2 is present in 99% of cases.
*Neuromuscular Disease*
Duchenne muscular dystrophy (DMD)	X-linked	Affected males often present with delayed milestones, and progressive muscle weakness and atrophy cause wheelchair dependency by age 13 with early death from respiratory and cardiac failure. DMD represents the severe end of the spectrum of dystrophinopathies.
*Neurodegenerative Disease*
Adrenoleukodystrophy	X-linked	The childhood cerebral form typically first presents with attention deficit disorder and progresses to cognitive, motor, vision, and hearing impairment, to complete disability within a few years. Widely variable expression even among individuals in the same family.
*Storage Disease*
Hunter syndrome	X-linked	A lysosomal storage disease that results in progressive excess storage of glycosaminoglycans. Symptoms include hepatosplenomegaly, CNS involvement, coarse facial features, and joint contractures. Respiratory and/or cardiac diseases are the major causes of morbidity and mortality. Onset and symptoms vary widely.
Pompe disease	Autosomal recessive	A glycogen storage disease that often presents with feeding difficulty, muscle weakness, hypotonia, and cardiomyopathy in the severe infantile-onset form. Without enzyme replacement therapy (ERT), infants often die in the first year of life.
*Skeletal Dysplasia*
Campomelic dysplasia	Autosomal dominant	Most individuals die during the neonatal period from respiratory insufficiency. Symptoms include severe laryngotracheomalacia, Pierre Robin sequence, ambiguous genitalia, club feet, bowed limbs, dislocated hips, and short stature. Cervical spine abnormalities, scoliosis, and kyphosis are common. Many females are found to be 46, XY.

Specific Care Challenges

The stigma, recurrence risk, and isolation that inherited life-threatening illnesses impart all affect attitudes and goals about the treatment plan.¹ Understanding the specific challenges faced by families and children affected by inherited life-threatening illnesses allows providers to respond to an individual family’s needs when broaching the subject of palliative care.

Stigma, guilt, and shame

The stigma associated with inherited disease stems from multiple sources. The effect of stigma is heavily influenced by personal, social, and cultural forces and therefore varies significantly from case to case. Understanding the impact of this stigma on individual patients and families is essential for introduction and maintenance of a palliative care plan.

The very concept of having passed on a life-threatening condition is a staggering source of guilt for many parents and grandparents. In conditions inherited through a single parent, this guilt can be unevenly distributed.² Feelings of guilt in a parent may influence decisions regarding both care meant to prolong life and care meant to improve quality of life. An overwhelming sense of responsibility may prevent some parents from asking for assistance. Although parental guilt is a normal response to having a child with an inherited illness, medical providers should be alert for signs of caregiver fatigue or family stress related to these feelings. Genetic counselors are specially trained to work with families around the time of initial diagnosis. The responses of family members often stem from a desire to find underlying meaning for the birth of a child with a genetic condition. Some parents may believe that a past action or inaction caused their child to have a birth defect or an inherited condition.³ Some parents are ashamed for having a child who does not fit the ideals they had prior to, or during, pregnancy.⁴ Some children or families who have particular difficulty adjusting to a genetic diagnosis may benefit from psychiatry or psychology consultations to discuss these feelings in greater detail.

Even aside from the issue of parental responsibility, genetic conditions are further stigmatizing society’s tendency to view a genetic difference as an inherent personal flaw. Medical staff should do all possible not to propagate this viewpoint. In fact, assessing the families’ experiences and listening to responses during initial consultations may give clues regarding feelings of guilt or shame. Patients or families experiencing shame will, at times, withdraw from the situation. Those experiencing an internal sense of responsibility or guilt may blame themselves, rationalize, or intellectualize the situation. Lack of control can be particularly painful for parents experiencing this unrealistic sense of responsibility.⁴ Actively engaging in medical decision making may allow families to feel that they have regained some control.