Crome syndrome

Overview

Crome syndrome is an exceptionally rare and fatal genetic disorder first described by Dr. L. Crome in the 1960s. It is classified as a multisystem congenital disorder, meaning it affects multiple organ systems from birth. The hallmark features of Crome syndrome include severe developmental abnormalities, neurological deficits, ocular anomalies (such as cataracts or microphthalmia), and renal (kidney) malformations. Most reported cases have occurred in infancy, with a poor survival rate and limited documented cases in medical literature, making it a poorly understood condition.

Causes

The precise genetic cause of Crome syndrome remains unknown, though it is presumed to be of genetic origin due to the congenital nature and multi-organ involvement. Given the limited number of reported cases, no specific gene mutation has been definitively linked to the syndrome. Some researchers suspect an autosomal recessive inheritance pattern, as the disorder may occur more frequently in consanguineous families, but further genetic studies are needed to confirm this hypothesis.

Symptoms

Crome syndrome presents with a variety of severe symptoms affecting several organ systems. The most commonly reported clinical features include:

• Microphthalmia or anophthalmia: Abnormally small or absent eyes

• Cataracts: Clouding of the eye lenses, often present at birth

• Severe developmental delay: Including profound intellectual disability and neurological deficits

• Hydrocephalus or brain malformations: Enlargement of fluid-filled spaces in the brain or structural abnormalities

• Kidney anomalies: Such as cystic dysplasia or agenesis (missing kidneys)

• Facial dysmorphism: Including a broad nasal bridge, low-set ears, or micrognathia (small jaw)

• Failure to thrive: Poor feeding and growth issues in infancy

Due to the syndrome’s severity, affected infants often have life-limiting complications shortly after birth.

Diagnosis

Diagnosis of Crome syndrome is challenging due to its rarity and overlap with other congenital syndromes. Diagnostic approaches include:

• Clinical evaluation: Identification of characteristic physical and neurological abnormalities in newborns

• Imaging studies: Brain MRI or CT to detect hydrocephalus or cerebral malformations

• Ophthalmologic exam: To assess for microphthalmia, cataracts, or retinal abnormalities

• Renal ultrasound: To detect kidney malformations or cystic changes

• Genetic testing: May help rule out similar syndromes or identify possible genetic causes, though no specific mutation has been confirmed for Crome syndrome

• Autopsy (in fatal cases): Often used in historical cases to describe internal anomalies and contribute to understanding

Treatment

There is no cure for Crome syndrome, and treatment is primarily supportive. Given the severity of organ involvement, especially neurological and renal systems, management is focused on comfort care and addressing individual symptoms where possible. Interventions may include:

• Supportive feeding: Nutritional support via feeding tubes in cases of feeding difficulty

• Ophthalmologic management: While visual outcomes are generally poor, cataracts may be assessed for potential surgery in less severe cases

• Neurological care: Management of seizures or hydrocephalus, if feasible

• Palliative care: In cases where multiple system failure or poor prognosis is evident

Prognosis

The prognosis for Crome syndrome is extremely poor. Most affected infants do not survive beyond early infancy due to the severity of congenital abnormalities, particularly affecting the brain and kidneys. For those who do survive longer, profound developmental impairment and multisystem complications persist. Due to its rarity, long-term outcomes are largely undocumented. Continued case reporting and genetic research are essential to improve diagnosis, understanding, and potential future interventions.