Kapur–Toriello syndrome

Overview

Kapur–Toriello syndrome is an extremely rare congenital disorder characterized by multiple craniofacial, developmental, and systemic abnormalities. First described by Kapur and Toriello in 1991, the syndrome includes features such as cleft lip and palate, distinctive facial appearance, anal atresia, and anomalies of the central nervous system. Fewer than a dozen cases have been reported in the medical literature, making it one of the least understood genetic syndromes. The condition is present from birth and typically identified due to its striking physical manifestations.

Causes

The exact genetic cause of Kapur–Toriello syndrome remains unidentified, though it is suspected to be of genetic origin based on the pattern of malformations and family history in some reported cases. Researchers believe it may result from de novo mutations or possibly autosomal recessive inheritance, but due to the rarity of the condition and limited number of cases, no specific gene has yet been confirmed as the cause.

Symptoms

The clinical features of Kapur–Toriello syndrome vary but commonly include:

• Midline cleft lip and/or palate

• Prominent nasal root and low-set ears

• Anal atresia or other anorectal malformations

• Brain anomalies such as agenesis of the corpus callosum

• Severe developmental delay and intellectual disability

• Feeding difficulties in infancy

• Microphthalmia (small eyes) or coloboma (eye defects)

• Congenital heart defects in some cases

Not all features are present in every case, and the severity of the condition can vary significantly.

Diagnosis

Diagnosis is primarily clinical, based on the presence of characteristic physical anomalies and developmental delays. Key diagnostic steps include:

• Detailed physical examination to identify craniofacial and systemic anomalies

• Imaging studies such as brain MRI to detect neurological defects

• Genetic testing, including chromosomal microarray or whole-exome sequencing, to rule out other syndromes and identify potential causative mutations

• Consultation with a clinical geneticist for evaluation and diagnosis

Given its rarity, diagnosis often requires exclusion of other more common syndromes with overlapping features.

Treatment

There is no cure for Kapur–Toriello syndrome, and treatment is supportive and tailored to the individual’s specific symptoms. Management typically involves a multidisciplinary approach, including:

• Surgical repair of cleft lip and/or palate

• Gastrointestinal surgery for anal atresia or feeding issues

• Early intervention with physical, occupational, and speech therapy

• Special education services for developmental support

• Ophthalmologic and neurologic evaluations and management

• Cardiology assessment if congenital heart defects are present

Prognosis

The prognosis for individuals with Kapur–Toriello syndrome depends on the severity of the anomalies and associated complications. Most individuals experience significant developmental delays and may have limited independence. Lifespan may be reduced in cases with severe congenital abnormalities, especially involving the brain or heart. However, supportive care can improve quality of life and help manage many of the challenges associated with the syndrome.