Summary about Disease
Zaki-Hennekam syndrome (ZKHS) is a rare genetic disorder characterized by a combination of distinctive facial features, neurological abnormalities, and skeletal malformations, particularly affecting the lymphatic system. It is considered a multiple congenital anomaly/mental retardation (MCA/MR) syndrome. The severity of the syndrome can vary considerably from person to person.
Symptoms
Symptoms of Zaki-Hennekam syndrome can vary but often include:
Facial features: Broad nasal bridge, prominent forehead, widely spaced eyes (hypertelorism), down-slanting palpebral fissures (eye openings), and a small jaw (micrognathia).
Neurological: Intellectual disability, developmental delay, seizures, hypotonia (low muscle tone).
Skeletal: Skeletal abnormalities such as scoliosis and hip dislocation.
Lymphatic: Lymphedema (swelling due to lymphatic fluid build-up), lymphangiectasia (dilated lymphatic vessels), chylothorax (fluid accumulation in the space around the lungs) and/or protein-losing enteropathy.
Other: Congenital heart defects, kidney abnormalities.
Causes
Zaki-Hennekam syndrome is caused by mutations in genes involved in the RAS/MAPK signaling pathway. Genes that have been linked to ZKHS include LYVE1, *PIK3R1*, and *CCSER1*. These genes play important roles in cell growth, differentiation, and survival. Mutations in these genes disrupt the normal function of these pathways, leading to the development of the characteristic features of the syndrome. The mode of inheritance is typically autosomal recessive, meaning both parents must carry a copy of the mutated gene for their child to be affected. *De novo* mutations (new mutations) can also occur.
Medicine Used
There is no specific cure for Zaki-Hennekam syndrome. Treatment focuses on managing the individual symptoms and complications associated with the condition.
Seizures: Antiepileptic medications.
Lymphedema: Compression therapy, physical therapy, and in some cases, surgery.
Heart defects: Medications or surgery depending on the type and severity of the defect.
Protein-losing enteropathy: Dietary modifications, medications to reduce inflammation, and/or intravenous immunoglobulin.
Developmental delays: Early intervention programs, speech therapy, occupational therapy, and physical therapy.
Is Communicable
Zaki-Hennekam syndrome is not communicable. It is a genetic disorder caused by gene mutations and cannot be spread from person to person.
Precautions
Since Zaki-Hennekam syndrome is a genetic condition, there are no specific precautions to prevent its occurrence. Genetic counseling is recommended for families with a history of the syndrome to assess the risk of having a child with the condition. Management of the condition involves regular medical check-ups and monitoring for complications to enable early intervention.
How long does an outbreak last?
Zaki-Hennekam syndrome is not caused by an infectious agent; therefore, the term "outbreak" is not applicable. It is a genetic condition that is present from birth. Symptoms may evolve and change over time, but the underlying genetic cause is constant.
How is it diagnosed?
Diagnosis of Zaki-Hennekam syndrome is based on a combination of clinical evaluation, physical examination, and genetic testing.
Clinical evaluation: Assessment of the individual's signs and symptoms.
Physical examination: Examination of the individual's physical features.
Genetic testing: Molecular genetic testing to identify mutations in genes known to be associated with Zaki-Hennekam syndrome, such as LYVE1, *PIK3R1*, and *CCSER1*.
Imaging studies: X-rays or other imaging may be used to assess skeletal abnormalities and/or lymphatic vessel abnormalities.
Timeline of Symptoms
The timeline of symptoms can vary considerably among affected individuals. Some symptoms may be present at birth (congenital), while others may develop later in infancy or childhood.
At birth/early infancy: Hypotonia, facial features, lymphedema, congenital heart defects, kidney abnormalities.
Infancy/childhood: Developmental delay, intellectual disability, seizures, skeletal abnormalities.
Throughout life: Lymphedema, protein-losing enteropathy, and other complications may persist or develop at any point in life.
Important Considerations
Multidisciplinary care: Management of Zaki-Hennekam syndrome requires a multidisciplinary approach involving specialists such as geneticists, neurologists, cardiologists, nephrologists, gastroenterologists, and therapists.
Early intervention: Early intervention programs and therapies are crucial for maximizing the individual's potential and improving their quality of life.
Family support: Support groups and counseling can provide valuable resources and support for families affected by Zaki-Hennekam syndrome.
Variable expression: The severity of symptoms can vary widely among individuals with Zaki-Hennekam syndrome, even within the same family.
Research: Continued research is needed to better understand the underlying mechanisms of the syndrome and develop more effective treatments.