Roberts syndrome

Overview

Roberts syndrome is a rare genetic disorder characterized by abnormalities in limb development (especially arms and legs), craniofacial anomalies, growth retardation, and sometimes intellectual disability. The syndrome is part of a group of conditions known as autosomal recessive cohesinopathies, which are caused by defects in the cohesion of chromosomes during cell division. Roberts syndrome is also known as SC Phocomelia syndrome, highlighting the severe limb malformations (phocomelia) that are often seen in affected individuals.

The severity of the disorder can range from mild to life-threatening. In some cases, babies are born with very short limbs or missing bones, and in severe cases, the condition can be fatal in the prenatal or neonatal period. Milder cases may survive into adulthood with significant physical disabilities. Early diagnosis and multidisciplinary care are essential for improving outcomes and supporting affected individuals and their families.

Causes

Roberts syndrome is caused by mutations in the ESCO2 gene located on chromosome 8 (8p21.1). The ESCO2 gene provides instructions for making a protein involved in the proper cohesion of sister chromatids during cell division (mitosis and meiosis). This process is crucial for accurate chromosome segregation and normal cellular development.

Genetic Inheritance:

• Roberts syndrome follows an autosomal recessive inheritance pattern.

• Both parents must carry one copy of the mutated gene for a child to be affected.

• When both parents are carriers, there is a 25% chance with each pregnancy that the child will inherit the disorder.

Mechanism:

• Mutations in the ESCO2 gene impair chromatid cohesion, leading to chromosomal abnormalities and improper development during embryogenesis.

• This results in growth arrest, malformations, and cellular instability, particularly affecting rapidly dividing tissues such as limbs and facial structures.

Symptoms

Symptoms of Roberts syndrome vary in severity but generally affect growth, limb development, facial structure, and other organ systems. The features are typically symmetrical and noticeable at birth.

Common Physical Features:

• Phocomelia: Severely shortened or absent limbs, particularly the upper limbs

• Micromelia: Generalized shortening of the arms and legs

• Facial abnormalities: Cleft lip and/or palate, wide-spaced eyes (hypertelorism), small head (microcephaly), prominent eyes

• Growth retardation: Both intrauterine and postnatal

• Small jaw (micrognathia)

Other Possible Symptoms:

• Intellectual disability: Mild to severe in some cases, but not present in all individuals

• Heart defects: Such as ventricular septal defects or patent ductus arteriosus

• Kidney malformations

• Genital abnormalities

• Hearing loss

Severe Forms:

• In severe cases, the disorder may result in stillbirth or early neonatal death

• Babies may be born with severe symmetrical limb reduction and multiple organ involvement

Diagnosis

Diagnosis of Roberts syndrome is based on clinical features, radiologic findings, cytogenetic analysis, and genetic testing. In severe cases, it can be diagnosed prenatally through ultrasound and confirmed with molecular studies.

Prenatal Diagnosis:

• Ultrasound: May detect limb abnormalities, cleft lip/palate, or growth retardation

• Amniocentesis or chorionic villus sampling (CVS): For genetic analysis of ESCO2 mutations

Postnatal Diagnosis:

• Physical examination: Limb defects, facial features, and growth patterns are typically suggestive

• Radiographic imaging: Reveals characteristic limb bone abnormalities (e.g., absent radii, ulnae, or femurs)

• Cytogenetic studies: May show premature centromere separation and heterochromatin repulsion

• Molecular genetic testing: Confirms mutations in the ESCO2 gene

Treatment

There is no cure for Roberts syndrome. Treatment is supportive and symptom-specific, involving a multidisciplinary team that may include pediatricians, orthopedic surgeons, cardiologists, speech and language therapists, and developmental specialists.

Supportive Care and Interventions:

• Orthopedic management: Surgical correction of limb deformities, use of prosthetics, and physical therapy

• Feeding support: For infants with cleft palate or feeding difficulties

• Speech therapy: Particularly in cases with cleft palate or developmental delay

• Cardiac care: For congenital heart defects, including possible surgical correction

• Special education services: If developmental delays or intellectual disabilities are present

Monitoring and Long-Term Management:

• Regular hearing and vision evaluations

• Monitoring for scoliosis or other orthopedic complications

• Psychosocial support for the child and family

Prognosis

The prognosis for Roberts syndrome varies greatly depending on the severity of symptoms. Severe cases, especially those with major organ malformations, may result in death during the neonatal period. Milder forms, particularly those without major internal abnormalities, may allow survival into adolescence or adulthood with appropriate medical care and support.

Functional outcomes depend on the degree of limb involvement and the presence of intellectual disability. Early intervention, rehabilitation services, and surgical care can significantly improve mobility and quality of life in less severely affected individuals.

Genetic counseling is strongly recommended for families with a history of Roberts syndrome to understand recurrence risks and explore reproductive options.