SNP Shot: Genomic Insights

Hennekam syndrome is a genetic disorder caused by problems in the development of the lymphatic system. This system is a vital part of both the circulatory and immune systems, consisting of a network of vessels that transport lymph fluid and immune cells throughout the body.

Key characteristics of Hennekam syndrome include abnormally widened lymphatic vessels (lymphangiectasia), especially those serving the intestines; swelling due to fluid buildup (lymphedema); and distinctive facial features.

Lymphangiectasia can obstruct lymph flow and lead to vessel rupture. In the intestines, this rupture can cause lymph fluid accumulation, disrupting nutrient, fat, and protein absorption. Fluid buildup in the abdomen can result in swelling called chylous ascites. Lymphangiectasia can also affect other organs, such as the kidneys, thyroid, lung lining (pleura), heart membrane (pericardium), or skin.

Lymphedema in Hennekam syndrome is often present at birth, primarily affecting the face and limbs. Severely affected infants may exhibit extensive swelling due to fluid accumulation before birth (hydrops fetalis). The lymphedema is usually more pronounced on one side of the body (asymmetric) and gradually worsens.

Facial features associated with Hennekam syndrome may include a flattened mid-face and nasal bridge, puffy eyelids, widely spaced eyes (hypertelorism), small ears, and a small mouth with enlarged gums (gingival hypertrophy). Affected individuals might also have an unusually small head (microcephaly) and premature fusion of skull bones (craniosynostosis).

Individuals with Hennekam syndrome commonly experience intellectual disability, ranging from mild to severe, although most cases are mild, and some individuals have normal intelligence. Growth delays, respiratory issues, permanently bent fingers and toes (camptodactyly), or fused skin between fingers and toes (cutaneous syndactyly) are also common.

Less common abnormalities in Hennekam syndrome include a shortage of red blood cells (anemia) due to iron deficiency, multiple spleens (polysplenia), misplaced kidneys, genital anomalies, an umbilical hernia, heart problems, hearing loss, excessive hair growth (hirsutism), a narrow or sunken chest (pectus excavatum), spinal curvature (scoliosis), and clubfeet.

The signs and symptoms of Hennekam syndrome vary considerably, even among family members. Life expectancy depends on the severity of the condition, ranging from childhood mortality to survival into adulthood.

Inheritance:

Hennekam syndrome follows an autosomal recessive inheritance pattern. This means that both copies of the responsible gene in each cell must have mutations for the condition to manifest. Parents of a child with an autosomal recessive disorder each carry one copy of the mutated gene but typically do not exhibit symptoms themselves.