The signs and symptoms of Hajdu-Cheney syndrome can vary greatly among affected individuals. The disorder is present at birth (congenital), but in some individuals the signs and symptoms may be more apparent during adolescence and adulthood.
Although researchers have been able to establish a clear syndrome with characteristic or “core” symptoms, much about the disorder is not fully understood. Several factors including the small number of identified cases, the lack of large clinical studies, and the possibility of other genes influencing the disorder prevent physicians from developing a complete picture of associated symptoms and prognosis. Therefore, it is important to note that affected individuals may not have all the symptoms discussed below. Parents should talk to their children’s physician and medical team about their specific case, associated symptoms and overall prognosis.
A characteristic finding is the breakdown of bone and tissue (osteolysis), particularly the outermost bones of the fingers and toes (acroosteolysis). This may be painless or can occur with inflammation, pain, Swelling and abnormal sensations like burning or tingling (paresthesia). In severe instances, the fingers and toes may be shortened and appear clubbed or rounded. Generally, the fingers are affected worse than the toes.
Some individuals also have a reduction of bone mass (osteoporosis), which predisposes individuals to fractures. Osteoporosis can be severe and fractures can be frequent. The bones of the spinal column, called the vertebrae, may be susceptible to compression fractures, in which the vertebrae collapse. This is extremely painful and can lead to spinal malformation. Some individuals may have abnormal sideways curvature of the spine (scoliosis) or an abnormal rounding of the spine (kyphosis) may occur. The long bones of the arms and legs can be misshapen or bowed. Because of these various skeletal problems, affected individuals may reach an adult height that is noticeably shorter than would otherwise be expected (short stature). Sometimes, these skeletal problems can become a significant impairment in daily life by late adolescent or early adulthood.
Individuals have distinctive facial features. Some features are noted during infancy or childhood, while others become more pronounced as affected individuals age. These features include eyes that are slightly farther apart than normal (mild hypertelorism); an abnormally wide space in between the upper and lower eyelids; a single, thick eyebrow over the eyes (synophrys); low-set ears, a high arched roof of the mouth (palate); a cleft palate; a Small jaw (micrognathia); flattening of the middle portion of the face; coarse hair; and a short neck. The range of motion of the neck may be limited.
There are also abnormalities of the skull including open sutures. An infant’s skull has seven bones and several joints called sutures. Sutures are made of tough, elastic fibrous tissue and separate the bones from one another. Sutures meet up (intersect) at two spots on the skull called fontanelles, which are better known as an infant’s “soft spots”. The seven bones of an infant’s skull usually fuse together until around age two or later. In affected adults, the occipital bone, which is located in the back of skull, may bulge outward, a condition called bathrocephaly.
Dental abnormalities are common including permanent teeth that get blocked as they try to emerge from the gums (impacted) and upper and lower teeth may not meet correctly when biting (malocclusion). There may be early loss of permanent teeth. The gums of affected individuals may be infected and swollen and bleed (periodontal disease).
Additional symptoms can include hearing loss, and joints that can be abnormally loose and flexible (joint hypermobility), and can be moved beyond their normal range. Various heart defects have been reported in some children. Abnormalities affecting the urinary tract can also occur. Some children experience protrusion of parts of the large intestine through an opening near the bellybutton (umbilical hernia).
Some affected individuals may have flattening of the base of the skull (platybasia). This may occur because the base of the skull is pushed upward because of basilar invagination. Basilar invagination occurs when the upper bones of the spinal column are located higher than normal, blocking the hole in the base of skull through which the spinal column passes. This blocks the flow of the fluid that surrounds the brain and spinal cord (cerebrospinal fluid). These conditions can cause excessive fluid accumulation and pressure within the brain (hydrocephalus), respiratory arrest, and sudden death.
A subset of affected individuals has polycystic kidney disease, which is the formation of cysts within the kidneys. This can cause Pain on both sides of the body between the last rib and hip (flank pain), blood in urine, and progressively poor function of the kidneys, which means that the kidneys will not be able to effectively remove waste products from the blood and excrete them in the urine.