SNP Shot: Genomic Insights

Congenital central hypoventilation syndrome (CCHS) is a condition affecting a person's ability to breathe normally. Individuals with CCHS often breathe shallowly (hypoventilate), particularly during sleep, leading to low oxygen levels and high carbon dioxide levels in their blood. Typically, the autonomic nervous system, which controls involuntary bodily functions, would respond to this imbalance by prompting deeper breathing or waking the individual. However, this response is impaired in those with CCHS. Consequently, they require assistance with breathing through mechanical ventilation or a diaphragm pacemaker, which stimulates a normal breathing rhythm. Some patients need this support constantly, while others only require it at night.

CCHS symptoms typically manifest shortly after birth, when affected infants begin to hypoventilate while asleep. The resulting oxygen deficiency can cause cyanosis, a bluish discoloration of the skin or lips. In milder cases, the presence of CCHS might not be recognized until later in life.

Beyond breathing difficulties, CCHS can disrupt the regulation of heart rate and blood pressure, particularly during exercise or positional changes. Individuals may also experience reduced pain sensitivity, low body temperature, and occasional episodes of excessive sweating.

Furthermore, CCHS can be associated with other nervous system problems. Approximately 20% of individuals with CCHS also have Hirschsprung disease, a condition affecting the nerves of the digestive tract. This leads to severe constipation, intestinal obstruction, and colon enlargement. (The combination of CCHS and Hirschsprung disease is sometimes referred to as Haddad syndrome.) Some individuals may experience learning disabilities or other neurological complications. People with CCHS also face a higher risk of developing specific nervous system tumors, including neuroblastomas, ganglioneuromas, and ganglioneuroblastomas.

Individuals with CCHS frequently exhibit eye abnormalities, such as a reduced pupillary response to light. Children with CCHS, in particular, may present with a characteristic short, wide, and somewhat flattened face, often described as "box-shaped."

In CCHS, life expectancy and intellectual development are impacted by the severity of the condition, the timing of diagnosis, and the effectiveness of treatment.

Inheritance:

CCHS follows an autosomal dominant inheritance pattern, meaning that only one copy of the mutated gene in each cell is needed to cause the disorder. In over 90% of CCHS cases, new mutations in the PHOX2B gene are responsible. These cases arise in individuals without a family history of the condition. Occasionally, an affected person inherits the mutation from a parent who also has CCHS. This occurrence is becoming more frequent as improved treatments enable more affected individuals to live to adulthood and have children. In roughly 5 to 10% of cases, individuals inherit the altered gene from an unaffected parent who carries the PHOX2B gene mutation only in their sperm or egg cells, a phenomenon called germline mosaicism. A parent exhibiting mosaicism for the PHOX2B gene mutation might not display any CCHS symptoms themselves.