Al-Raqad syndrome

Overview

Al-Raqad Syndrome is an extremely rare genetic disorder characterized by a distinct combination of developmental delay, craniofacial abnormalities, congenital heart defects, and limb anomalies. The syndrome was first described in 2016 by Dr. Mohammed Al-Raqad and colleagues, following the identification of several children in a consanguineous Jordanian family who shared similar clinical features and a novel genetic mutation.

Due to the limited number of reported cases, the full clinical spectrum of Al-Raqad Syndrome is not yet fully understood, but its diagnosis typically involves a combination of physical features, developmental signs, and confirmatory genetic testing.

Causes

Al-Raqad Syndrome is caused by a mutation in the HIVEP2 gene (also known as MIBP1), which plays a role in gene transcription regulation in neuronal and other cell types. The inheritance pattern is believed to be autosomal recessive, meaning both copies of the gene must carry the mutation for the condition to manifest.

The condition is more likely to occur in populations where consanguinity (marriage between close relatives) is common, due to the increased likelihood of inheriting two copies of the faulty gene.

Symptoms

The symptoms of Al-Raqad Syndrome can vary in severity, but commonly reported clinical features include:

Neurological and Developmental Features:

• Global developmental delay

• Intellectual disability

• Hypotonia (low muscle tone)

Craniofacial Abnormalities:

• Microcephaly (small head size)

• Prominent forehead

• Hypertelorism (widely spaced eyes)

• Depressed nasal bridge

• Low-set ears

Cardiac and Other Systemic Features:

• Congenital heart defects (e.g., atrial septal defect)

• Limb anomalies (such as overlapping toes or joint stiffness)

• Growth retardation

Diagnosis

Diagnosing Al-Raqad Syndrome involves clinical recognition of the characteristic features, supported by genetic testing. Key diagnostic steps include:

• Physical and neurological examination: To assess growth, craniofacial structure, tone, and reflexes

• Cardiac evaluation: Echocardiography to detect congenital heart defects

• Developmental assessment: Evaluating cognitive and motor milestones

• Genetic testing: Whole-exome sequencing or targeted testing to identify HIVEP2 mutations

• Family history: Helpful in consanguineous families or those with previously affected children

Treatment

There is no cure for Al-Raqad Syndrome. Treatment is supportive and aims to address specific symptoms and improve quality of life. Interventions include:

• Developmental therapies: Physical, occupational, and speech therapy

• Special education services: For intellectual and learning disabilities

• Cardiology follow-up: Monitoring and surgical correction if congenital heart defects are present

• Orthopedic support: Braces or surgical management for limb anomalies

• Genetic counseling: For families with a known mutation, especially in populations with high consanguinity

Prognosis

The long-term prognosis of Al-Raqad Syndrome is not yet well defined due to the rarity of the condition. Most individuals experience significant developmental and intellectual challenges. Early diagnosis and comprehensive supportive care can help improve developmental outcomes and quality of life, though affected individuals may require lifelong assistance with daily activities.

As more cases are identified and studied, the understanding of disease progression and management is expected to improve.