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Halal syndrome
A rare genetic syndrome with cleft lip/palate, polydactyly, and intellectual disability.
Overview
Halal syndrome, also known as Halal–Fraser syndrome, is a rare congenital disorder that falls under the broader category of Fraser syndrome. It is characterized by a spectrum of developmental abnormalities including cryptophthalmos (where the skin is continuous over the eyes), syndactyly (fused fingers or toes), and urogenital malformations. First described by Fadel Halal and colleagues, the syndrome is often identified at birth due to its distinct physical features and may be associated with significant morbidity and mortality depending on the severity of organ involvement.
Causes
Halal syndrome is caused by mutations in genes involved in embryonic development, particularly the FRAS1, FREM2, and GRIP1 genes. These genes play crucial roles in skin and organ development. The syndrome follows an autosomal recessive inheritance pattern, meaning both parents must carry a defective gene copy for the disorder to appear in their child. Consanguineous parentage (parents who are closely related) increases the risk of inheriting the syndrome.
Symptoms
The clinical presentation of Halal syndrome varies widely but commonly includes:
Cryptophthalmos: Eyelids are absent, and the skin is continuous over the eye, often resulting in blindness.
Syndactyly: Fusion of fingers or toes, ranging from simple skin fusion to bony fusion.
Urogenital anomalies: Malformations of the kidneys, urinary tract, or external genitalia.
Facial abnormalities: Including a broad nasal bridge, low-set ears, and cleft lip or palate.
Laryngeal or respiratory defects: In some cases, structural airway defects may be present.
Renal agenesis or dysplasia: Absence or malformation of one or both kidneys, which can be life-threatening.
Diagnosis
Diagnosis of Halal syndrome is based on clinical findings, imaging, and genetic testing. Key diagnostic steps include:
Physical examination: Observation of characteristic malformations at birth.
Prenatal imaging: Ultrasound may detect renal agenesis or other structural abnormalities during pregnancy.
Genetic testing: Molecular analysis to identify mutations in FRAS1, FREM2, or GRIP1 genes can confirm the diagnosis.
Autopsy (in fatal cases): May be used to confirm diagnosis and aid in genetic counseling for the family.
Treatment
Treatment is highly individualized and depends on the severity and combination of anomalies. Management may include:
Surgical interventions: Correction of syndactyly, cryptophthalmos, cleft lip/palate, and urogenital anomalies.
Supportive care: For infants with kidney defects, respiratory issues, or feeding difficulties.
Multidisciplinary management: Teams involving pediatricians, surgeons, ophthalmologists, nephrologists, and geneticists are often required.
Genetic counseling: Recommended for parents and family members to understand inheritance risk and options in future pregnancies.
Prognosis
The prognosis of Halal syndrome varies significantly depending on the severity of the anomalies. Cases with bilateral renal agenesis or severe respiratory tract malformations often result in perinatal death. Children with milder forms may survive and benefit from surgical and supportive interventions, though they may face lifelong challenges related to vision, mobility, and organ function. Early diagnosis, coordinated care, and parental support are key factors in improving quality of life and long-term outcomes.
Medical Disclaimer
The information provided on this page is for educational purposes only and is not a substitute for professional medical advice, diagnosis, or treatment. Always seek the advice of your physician or other qualified health provider with any questions you may have regarding a medical condition.