CAMFAK syndrome

Overview

CAMFAK syndrome is a very rare, inherited neurodegenerative disorder primarily affecting the central and peripheral nervous systems. The name CAMFAK is an acronym derived from its key features: Cerebellar hypoplasia, Agenesis of the corpus callosum, Mental retardation, Facial anomalies, Axonal neuropathy, and Kidney (renal) abnormalities. This syndrome is typically identified in infancy or early childhood, and it often results in significant developmental and physical impairment. CAMFAK is part of a group of conditions known as hereditary motor and sensory neuropathies with central nervous system involvement.

Causes

CAMFAK syndrome is thought to be caused by autosomal recessive genetic mutations, meaning a child must inherit one mutated copy of the gene from each parent to be affected. Although the specific gene responsible for CAMFAK has not been definitively identified in all cases, the condition is believed to be part of a spectrum of leukodystrophies and neuropathies involving abnormalities in neuronal development and maintenance. Consanguinity (parents who are related by blood) has been noted in some reported cases, supporting autosomal recessive inheritance.

Symptoms

The clinical presentation of CAMFAK syndrome includes a combination of central and peripheral nervous system abnormalities along with craniofacial and renal features. Reported symptoms may include:

• Cerebellar hypoplasia – underdevelopment of the cerebellum, leading to poor coordination and balance

• Agenesis of the corpus callosum – absence of the structure connecting the two cerebral hemispheres, contributing to developmental delays

• Severe intellectual disability – previously termed mental retardation

• Facial dysmorphism – including a prominent forehead, flat nasal bridge, and low-set ears

• Axonal neuropathy – affecting motor and sensory nerves, leading to muscle weakness, hypotonia, and reduced reflexes

• Renal anomalies – such as hypoplastic or dysplastic kidneys

• Seizures or abnormal EEG findings in some cases

• Delayed or absent developmental milestones

Diagnosis

Diagnosis of CAMFAK syndrome is complex and typically involves multiple diagnostic tools and specialists. Evaluation includes:

• Neuroimaging (MRI) – to identify cerebellar hypoplasia and agenesis of the corpus callosum

• Nerve conduction studies – to assess axonal neuropathy

• Developmental and cognitive assessments – to evaluate intellectual and motor function

• Renal ultrasound or imaging – to detect kidney abnormalities

• Genetic testing – may help identify underlying mutations, though specific markers for CAMFAK are not always found

• Family history – including assessment of consanguinity and similar presentations in siblings or relatives

Treatment

There is no cure for CAMFAK syndrome. Management is supportive and focuses on improving quality of life and addressing specific symptoms. Treatment options may include:

• Physical therapy – to address hypotonia and improve mobility

• Occupational therapy – for developmental skills and adaptive techniques

• Speech and language therapy – if the child has speech or feeding difficulties

• Anticonvulsants – for seizure management if needed

• Nephrology follow-up – for managing renal abnormalities and preventing complications

• Multidisciplinary care – involving neurologists, developmental pediatricians, nephrologists, and genetic counselors

Prognosis

The prognosis for CAMFAK syndrome is generally poor due to the severity of neurological and systemic involvement. Affected individuals typically experience profound developmental delays and may be unable to walk or speak. Life expectancy may be shortened, especially if renal complications or severe neurological symptoms are present. However, prognosis can vary depending on the specific clinical features and access to supportive care. Early diagnosis, symptom-specific interventions, and coordinated care can improve comfort and quality of life for affected individuals and their families.