NORD gratefully acknowledges Dr. Renita Castelino, Reader, Department of Oral Medicine and Radiology, NITTE University, Mangalore, India, for assistance in the preparation of this report.
Hanhart syndrome is a rare birth defect in which the most obvious signs are a short, incompletely developed tongue (hypoglossia); absent or partially missing fingers and/or toes (hypodactylia); malformed arms and/or legs (peromelia); and an extremely small jaw (micrognathia)..The severity of these physical abnormalities varies greatly from person to person. Children with this disorder often have some, but not all, of the symptoms.Intelligence is normal. The cause of Hanhart syndrome is not fully understood.
Hanhart syndrome is in the group of conditions known as Oromandibular-limb hypogenesis syndromes (OLHS). These syndromes are characterized by underdevelopment of the limbs, mouth and jaw.
Hanhart syndrome was first described in 1932. In 1950, Dr. Hanhart described three different cases of aglossia with associated limb defects and the name ‘Hanhart syndrome’ was adopted.
The craniofacial abnormalities include microstomia (small mouth); micrognathia (small jaw and deeply receding jaw); hypoglossia; cleft palate; clefting of the tongue; broad nose; telecanthus; lower eyelid defects; facial asymmetry; mandibular hypodontia and partial absence of mandible (jaw).
In children with Hanhart syndrome, fingers and/or toes may be partially missing or completely absent (ectrodactylia). In addition, lower (distal) portions of the arms and/or legs may be malformed, partially missing, and/or completely absent (amelia). In an affected individual, any limb malformations present tend to vary in severity from limb to limb (asymmetric).
In infants with Hanhart syndrome, loss of some motor function (paralysis) in the facial area may be present at birth (congenital) due to impairment of 1 or more of the 12 nerve pairs that arise from the brain (cranial nerve palsy). In many cases, congenital nerve palsy of the 6th (abducens) and/or 7th (facialis) cranial nerves is present. In rarer cases, the 3rd (oculomotorius), 5th (trigeminus), 9th (glossopharyngeus), and/or 12th (hypoglossus) cranial nerves are affected. The presence of some of these nerve palsies can worsen any feeding problems that occur because of tongue, mouth, and/or jaw abnormalities.
Additional abnormalities may occur in association with Hanhart syndrome. In some affected individuals, the spleen and the gonads (i.e., testes in males, ovaries in females) may have fused together during fetal development (splenogonadal fusion). This may be manifested in males as a testicular mass or as a testis that has failed to descend into the scrotum (cryptorchidism). Some individuals may have vertical skin folds that cover the eyes’ inner corners (epicanthus); a malformation of the foot (clubfoot or talipes); an absent kidney (unilateral renal agenesis); a cyst in the brain (porencephalic cyst); and/or an absent or abnormally located anus (imperforate anus). Obstruction of the central portion of the small intestine (jejunal atresia) may occur due to twisting of the small intestine. Intellectual disability may also be present in some individuals with Hanhart syndrome.
The exact cause of Hanhart syndrome is not known. Cases tend to occur randomly, with no apparent cause (sporadic). Some researchers believe that the disorder, which has been reported in the children of blood relatives (consanguinity) in a number of cases, may be inherited as an autosomal recessive genetic trait.
Recessive genetic disorders occur when an individual inherits two copies of an abnormal gene for the same trait, one from each parent. If an individual inherits one normal gene and one gene for the disease, the person will be a carrier for the disease but usually will not show symptoms. The risk for two carrier parents to both pass the altered gene and have an affected child is 25% with each pregnancy. The risk to have a child who is a carrier like the parents is 50% with each pregnancy. The chance for a child to receive normal genes from both parents is 25%. The risk is the same for males and females.
Parents who are close relatives (consanguineous) have a higher chance than unrelated parents to both carry the same abnormal gene, which increases the risk to have children with a recessive genetic disorder.
Some clinicians theorize that the defect in development responsible for Hanhart syndrome may occur when there is an hemorrhagic lesion or an interruption of the necessary blood supply to the parts of the embryo that eventually develop into the arms, legs, hands, and feet (the limb buds); the tongue; the mouth and jaw area (Meckel’s cartilage); and, possibly in some cases, parts of the brain. It is projected that a clot has formed within a blood vessel (thrombus) or has traveled through the blood stream and become lodged in a vessel (embolus) is responsible for the interruption of blood flow. Such a clot may result from exposure of the embryo to certain drugs taken during pregnancy that decrease blood flow (hypoperfusion) through particular organs. Or a clot could result from the death of another embryo in the uterus that was originally formed from the same fertilized egg (discordant monozygotic twins).
Hanhart syndrome is a very rare developmental disorder that affects males and females in equal numbers. Fewer than 1 in 20,000 children are affected with this disorder. Approximately 30 cases of Hanhart syndrome were reported in the medical literature from 1932 to 1991.
Hanhart syndrome is detected in the neonate (newborn), based upon a thorough clinical evaluation and characteristic physical findings. Signs of Hanhart syndrome may be identified before birth (prenatally) by ultrasonography, a test that creates an image of the fetus by measuring the reflection of sound waves.
The treatment of Hanhart syndrome requires the coordinated efforts of a team of specialists. Pediatricians, plastic and orthopedic surgeons, dental specialists, speech pathologists, physical therapists, and others must systematically and comprehensively plan the child’s treatment.
In infants with Hanhart syndrome, any feeding difficulties resulting from tongue, mouth, and/or jaw malformations and cranial nerve palsies must be addressed immediately to ensure proper nutrition and growth. Abnormalities of the tongue, mouth, and jaw area may be treated through surgical correction, the use of artificial devices (prostheses), and/or physical therapy.
Children with Hanhart syndrome may have difficulties with speech, depending on the severity of any tongue, mouth, and/or jaw malformations and the progress of any treatment to correct these physical abnormalities. Treatment for such impairment consists of specialized speech therapy.
Depending on the severity of any limb abnormalities, children with Hanhart syndrome may have difficulty performing skills that require coordination of motion (motor skills), such as walking, writing, etc. Treatment may consist of surgery; the use of artificial replacements for parts of the arms, legs, hands, and/or feet that may be missing (limb prostheses); and/or physical therapy to help individuals enhance their motor skills.
Genetic counseling will be of benefit for patients and their families. Individuals with Hanhart syndrome may also benefit from special social support, special education, and vocational and occupational services. Other treatment is symptomatic and supportive, based upon the specifics of the affected individual’s case.
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