About hard syndrome

What is hard +/-e syndrome?

Walker-Warburg syndrome (WWS) is a rare multisystem disorder characterized by muscle, brain and eye abnormalities, often leading to death in the first weeks of life. However, the specific symptoms and severity of WWS can vary greatly from case to case. The most consistent features are (1) a smooth appearance of the surface of the brain due to lack of normal folding pattern (lissencephaly or agyria), often with malformations of other brain structures including the cerebellum and brain stem, (2) various developmental abnormalities of the eye and (3) progressive degeneration and weakness of the voluntary muscles which is called congenital muscular dystrophy. WWS demonstrates autosomal recessive inheritance, with a recurrence risk of 1 in 4 or 25% for a couple who has previously had a child diagnosed with this genetic condition.

WWS is a severe form of the broader spectrum of conditions referred to as CMD (congenital muscular dystrophy), which is a group of disorders characterized by weakness and atrophy of various voluntary muscles of the body. Approximately 30 different disorders make up the muscular dystrophies. These disorders affect different muscles, may or may not have other body systems involved, and have different ages of onset, severity and inheritance patterns. The disorder was first reported in the medical literature in 1942.

What are the symptoms for hard +/-e syndrome?

The CranioFacial abnormalities in children with Hanhart syndrome can include a small mouth (microstomia); small jaw and deeply receding jaw (micrognathia); shorty, incompletely developed tongue (hypoglossia); cleft palate; cleft tongue; broad nose; increased distance between the inner corners of the eyelids (telecanthus); lower eyelid defects; facial asymmetry; and partial absence of the jaw (mandibular hypodontia).

Affected children may have fingers and/or toes that are 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). Limb malformations may vary in severity from limb to limb (asymmetric).

Infants with Hanhart syndrome may have loss of some motor function (paralysis) in the facial area at birth due to impairment of one 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 inner corners of the eyes (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 be present in some individuals with Hanhart syndrome.

What are the causes for hard +/-e 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 in an autosomal recessive pattern.

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).

What are the treatments for hard +/-e syndrome?

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.

Infants with Hanhart syndrome may have feeding difficulties resulting from tongue, mouth, and/or jaw malformations and cranial nerve palsies that 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 benefit from speech therapy if speech is affected by tongue, mouth, and/or jaw malformations.

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.

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.

Genetic counseling is recommended for patients and their families.

What are the risk factors for hard +/-e syndrome?

Congenital muscular dystrophy in its most severe form, hard +/-e syndrome, is accompanied by abnormalities of the brain and eyes. Typical signs and symptoms include hypotonia, muscle weakness, developmental delay, intellectual dysfunction, and sporadically occurring seizures. Lissencephaly, hydrocephalus, cerebellar deformities, eye abnormalities, and other abnormalities are also linked to it. Although the genetic etiology is unknown in many cases, it may be brought on by genetic alterations in any of a number of genes, including the POMT1, POMT2, and FKRP genes. The hard +/-e syndrome has an autosomal recessive inheritance pattern.

Risk factor

1. The majority of those affected by Hard +/-e syndrome are at risk because they do not live past the age of three due to the severity of the problems it causes.
2. There are so many risk factors for this syndrome.
3. Skeletal muscles, which the body utilizes to move, are impacted by hard +/-e syndrome.
4. Babies who are affected exhibit hypotonia, or weak muscular tone, and are commonly referred to as "floppy." Over time, the muscle weakness gets worse.
5. The brain is also affected by hard +/-e syndrome; those who have it commonly have a brain anomaly termed cobblestone lissencephaly, in which the brain's surface lacks the folds and grooves it normally has and instead takes on a bumpy, irregular look (like that of cobblestones).

Symptoms
Congenital muscular dystrophy,Weakening and loss of muscle at birth,Abnormalities of the brain and eyes,Hypotonia,Develop contractures,Serious brain findings
Conditions
Conditions of hard +/-e are congenital (present at birth), and some of the brain abnormalities can be detected by prenatal ultrasound and/or fetal MRI in the later stages of pregnancy,Individuals with hard +/-e have congenital muscular dystrophy, or a weakening and loss of muscle at birth
Drugs
NA

Is there a cure/medications for hard +/-e syndrome?

A genetic condition called hard +/-e syndrome affects how the muscles, brain, and eyes grow. It is the most severe instance of a class of genetic disorders called congenital muscular dystrophies, which result in early-life muscle weakening and atrophy. Hard +/-e syndrome's warning signs and symptoms appear at birth or in the first few months of life. The majority of those affected by Hard +/-e syndrome do not live past the age of three due to the severity of the problems it causes.

Since there is no known cure for the hard +/-e syndrome, each patient's symptoms will determine how the disease is managed. In order to treat the disorder's symptoms or to assist parents in caring for their children, doctors may collaborate with parents.

Treatment

1. Currently, there is no available cure for the hard +/-e syndrome; instead, treatment is tailored to each patient's unique set of symptoms.
2. To carefully and thoroughly arrange a child's treatment, medical management may call for the coordinated efforts of a team of specialists, including pediatricians, geneticists/genetic counselors, orthopedic surgeons, neurologists, ophthalmologists, and other health care providers.
3. Treatment options for hard +/-e syndrome include surgery to insert shunts to drain extra cerebrospinal fluid and lower the pressure inside the brain, anti-seizure medication, and physical therapy to strengthen muscles and prevent contractures.
4. To help them feed, some kids may require a gastric tube

Symptoms
Congenital muscular dystrophy,Weakening and loss of muscle at birth,Abnormalities of the brain and eyes,Hypotonia,Develop contractures,Serious brain findings
Conditions
Conditions of hard +/-e are congenital (present at birth), and some of the brain abnormalities can be detected by prenatal ultrasound and/or fetal MRI in the later stages of pregnancy,Individuals with hard +/-e have congenital muscular dystrophy, or a weakening and loss of muscle at birth
Drugs
NA

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