SNP Shot: Genomic Insights

Hajdu-Cheney syndrome is a rare condition affecting various parts of the body, most notably the bones. A key characteristic is acro-osteolysis, the loss of bone tissue in the hands and feet. This leads to short, broad fingers and toes that may shorten further as the bone tips deteriorate. Bone loss in the fingers can impair fine motor skills like picking up small items.

Bone abnormalities are widespread in this syndrome. Osteoporosis is common, making bones fragile and prone to fractures. Many experience compression fractures in the vertebrae, and some develop scoliosis or kyphosis (abnormal spinal curvature). The long bones of the arms and legs are also affected, leading to short stature.

Skull bone abnormalities, including facial bones, are also typical. The skull is often dolichocephalic (elongated). A prominent occiput (a bump at the back of the skull) is frequently observed. Distinct facial features include widely spaced, downward-slanting eyes, synophrys (eyebrows that merge), low-set ears, midface hypoplasia (sunken midface), and a long philtrum (space between nose and upper lip). Some children are born with a cleft or high-arched palate. Facial features are often described as "coarse" in affected adults.

Additional features sometimes seen in individuals with Hajdu-Cheney syndrome include joint hypermobility (excessive range of motion), dental problems, hearing loss, a deep voice, excessive body hair, recurrent childhood infections, heart defects, and kidney abnormalities like polycystic kidneys (multiple cysts).

The most serious complications, occurring in roughly half of affected individuals, are platybasia and basilar invagination. Platybasia is a flattening of the skull base due to bone thinning. Basilar invagination involves the spine protruding into the skull, pressing on the lower brain. These can cause severe neurological issues like headaches, vision and balance problems, hydrocephalus (fluid buildup in the brain), breathing problems, and even sudden death.

The signs and symptoms of Hajdu-Cheney syndrome vary significantly, even within families. Features like acro-osteolysis and certain facial characteristics may not be present at birth, appearing later in childhood or adulthood. The risk of platybasia and basilar invagination also increases with age.

Hajdu-Cheney syndrome shares significant overlap with serpentine fibula-polycystic kidney syndrome (SFPKS). Formerly considered separate, research has revealed that both are linked to mutations in the same gene (NOTCH2). Consequently, many researchers now consider them variants of the same condition.

Inheritance:

Hajdu-Cheney syndrome follows an autosomal dominant inheritance pattern. This means that only one copy of the mutated NOTCH2 gene is enough to cause the disorder. Most cases arise from new gene mutations in individuals with no family history. Less often, the mutation is inherited from an affected parent.