Potocki–Shaffer syndrome

Overview

Potocki–Shaffer syndrome (PSS) is a rare genetic disorder characterized by a distinctive pattern of craniofacial abnormalities, intellectual disability, multiple exostoses (benign bone tumors), and enlarged parietal foramina (openings in the skull). It results from a deletion of genetic material on the short arm of chromosome 11 (11p11.2-p12), affecting several critical genes. First described by Drs. Lorraine Potocki and Lisa Shaffer, the syndrome exhibits a variable range of clinical manifestations depending on the size and genes involved in the chromosomal deletion. The condition is considered a contiguous gene deletion syndrome, meaning multiple genes within a deleted chromosomal region contribute to the phenotype.

Causes

Potocki–Shaffer syndrome is caused by a deletion of a segment on chromosome 11p11.2-p12. The loss of multiple genes in this region leads to the various symptoms seen in affected individuals. Two key genes commonly deleted include:

• EXT2 (exostosin glycosyltransferase 2): Loss of this gene is responsible for multiple osteochondromas (bone tumors).

• ALX4 (aristaless-like homeobox 4): Deletion causes enlarged parietal foramina due to abnormal skull development.

The chromosomal deletion usually occurs sporadically as a new (de novo) event during the formation of reproductive cells or in early embryonic development. In rare cases, it may be inherited in an autosomal dominant manner from a parent with a balanced chromosomal rearrangement or mild form of the condition.

Symptoms

The clinical presentation of Potocki–Shaffer syndrome varies depending on the extent of the chromosomal deletion. Common signs and symptoms include:

• Craniofacial anomalies: Enlarged parietal foramina, high forehead, broad nasal bridge, and wide-set eyes (hypertelorism)

• Multiple exostoses (osteochondromas): Benign bone growths, especially near the long bones and joints, which may cause pain, restricted movement, or skeletal deformities

• Intellectual disability: Usually moderate to severe, with delayed developmental milestones and speech impairments

• Hypotonia: Low muscle tone, particularly noticeable in infancy

• Delayed motor skills: Including late sitting, walking, and fine motor development

• Vision problems: Such as strabismus or refractive errors

• Hearing loss: May be present in some individuals

• Seizures: Reported in a subset of patients

• Short stature: Due to skeletal anomalies

• Other skeletal abnormalities: Including scoliosis or limb length discrepancies

Diagnosis

Diagnosis of Potocki–Shaffer syndrome is confirmed through genetic testing. The process generally includes:

• Clinical evaluation: Based on the presence of characteristic physical features and developmental delay

• Chromosomal microarray analysis (CMA): Detects the deletion on chromosome 11p11.2-p12 and identifies the specific genes involved

• FISH (fluorescence in situ hybridization): May be used to confirm the deletion in targeted cases

• Karyotyping: Can detect large chromosomal abnormalities but may miss small deletions

• Parental genetic testing: Recommended to determine if the deletion is inherited or de novo

• Imaging studies: Skull X-rays or CT scans can identify parietal foramina; X-rays of limbs may show exostoses

Treatment

There is no cure for Potocki–Shaffer syndrome, and treatment focuses on managing individual symptoms through a multidisciplinary approach. Common interventions include:

Developmental and Educational Support

• Early intervention programs with speech, occupational, and physical therapy

• Special education services tailored to cognitive and behavioral needs

• Assistive communication devices for speech impairments

Medical and Surgical Care

• Orthopedic surgery for painful or disabling bone exostoses

• Routine monitoring of bone growth and skeletal alignment

• Vision and hearing assessments with corrective treatments as needed

• Anticonvulsant medication for seizure management

Other Interventions

• Genetic counseling for families

• Psychological and behavioral therapy for emotional and social development

Prognosis

The prognosis for individuals with Potocki–Shaffer syndrome depends on the severity of symptoms and the extent of the chromosomal deletion. While intellectual and physical disabilities may be lifelong, supportive therapies and medical care can greatly improve quality of life and functional abilities. Bone exostoses may cause increasing problems during childhood and adolescence but are often manageable with orthopedic interventions. Early diagnosis and a coordinated care approach are essential for optimizing developmental outcomes and managing complications associated with this complex genetic condition.