Crandall syndrome

Overview

Crandall syndrome is a rare genetic disorder characterized by a triad of clinical features: sensorineural hearing loss, sparse or absent hair (hypotrichosis), and hypogonadism (underdevelopment of the sexual organs and reduced hormone levels). It is considered a variant of another condition called Björnstad syndrome but with the addition of hormonal involvement. Crandall syndrome typically presents in early childhood and affects both males and females, though hypogonadism is often more pronounced in males.

Causes

Crandall syndrome is believed to be inherited in an autosomal recessive pattern, meaning a child must inherit one copy of the mutated gene from each parent. Though the exact gene responsible for Crandall syndrome has not been definitively identified, it is closely related to Björnstad syndrome, which is associated with mutations in the BCS1L gene. This gene plays a role in mitochondrial function, and its disruption may affect tissues that are highly energy-dependent, including the auditory system, hair follicles, and endocrine glands.

Symptoms

Common clinical features of Crandall syndrome include:

• Sensorineural hearing loss: Hearing impairment due to inner ear or auditory nerve dysfunction, usually present from birth or early childhood

• Hypotrichosis: Sparse, brittle, or absent scalp hair; may also affect eyebrows and eyelashes

• Hypogonadism: Delayed or absent puberty, reduced levels of sex hormones (testosterone or estrogen), and underdeveloped secondary sexual characteristics

Additional findings may include infertility in adulthood, particularly in males, and mild developmental delays or growth issues in some cases, though these are not consistently observed.

Diagnosis

Diagnosis of Crandall syndrome is based on clinical features and may be supported by laboratory tests and genetic studies. Diagnostic steps include:

• Physical examination: Observation of hair abnormalities and signs of delayed puberty

• Hearing tests (audiometry): To assess the degree and type of hearing loss

• Hormonal assays: Blood tests to evaluate levels of sex hormones such as testosterone, estrogen, luteinizing hormone (LH), and follicle-stimulating hormone (FSH)

• Genetic testing: May be used to rule out related conditions or identify mutations in the BCS1L gene

• Family history assessment: To identify potential autosomal recessive inheritance patterns

Treatment

There is no cure for Crandall syndrome, so treatment focuses on managing symptoms and improving quality of life. A multidisciplinary approach involving audiologists, endocrinologists, dermatologists, and genetic counselors is often recommended. Treatment options include:

• Hearing aids or cochlear implants: To improve hearing function

• Hormone replacement therapy (HRT): Testosterone for males or estrogen/progesterone for females to support sexual development and overall health

• Cosmetic and dermatological care: For scalp and hair management, including use of wigs or scalp treatments

• Fertility counseling: In adulthood for individuals with reproductive concerns

• Genetic counseling: For affected families and carriers to understand inheritance risks and options

Prognosis

The prognosis for individuals with Crandall syndrome is generally favorable with proper management of hearing loss and hormone deficiencies. While the syndrome may lead to challenges in communication, sexual development, and self-esteem, early diagnosis and a supportive care plan can enable affected individuals to lead fulfilling lives. Fertility may be impaired, especially in males, and lifelong hormone therapy may be required. Regular follow-up and multidisciplinary care are essential to monitor and address evolving health needs.