Nevo syndrome

Overview

Nevo syndrome, also known as Nevo hyperelasticity syndrome, is an extremely rare congenital connective tissue disorder characterized by features that overlap with other overgrowth syndromes, particularly Ehlers-Danlos syndrome and Weaver syndrome. It is primarily distinguished by marked tissue laxity, joint hypermobility, soft and hyperextensible skin, overgrowth, and distinct facial and skeletal anomalies. First described by S. Nevo in 1972, this syndrome is typically apparent at birth or in early infancy.

Due to its rarity, very few cases of Nevo syndrome have been reported in the medical literature. The condition is often grouped under the umbrella of congenital overgrowth and connective tissue disorders, and may present diagnostic challenges due to its overlap with other syndromes affecting skin and skeletal development.

Causes

Nevo syndrome is believed to follow an autosomal recessive inheritance pattern, meaning both copies of a causative gene (one from each parent) must be mutated for a child to develop the condition. Although the precise genetic mutation responsible for Nevo syndrome has not been definitively identified, it is suspected to involve genes associated with collagen formation or connective tissue integrity, given the similarities to Ehlers-Danlos syndrome.

The rarity of the syndrome and limited number of documented cases have made it difficult to pinpoint a specific gene, though ongoing advancements in whole-genome and exome sequencing may eventually clarify its genetic basis.

Symptoms

Nevo syndrome presents with a range of distinctive features, affecting multiple systems including the skin, skeleton, and nervous system. Symptoms are typically noticeable at birth and may progress with age.

Cutaneous and Connective Tissue Features

• Soft, hyperextensible skin that bruises easily

• Generalized tissue laxity and skin fragility

• Joint hypermobility or contractures

• Loose and redundant skin folds

Skeletal and Growth Abnormalities

• Macrosomia (excessive birth weight and length)

• Overgrowth in infancy and early childhood

• Flexion contractures (permanently bent joints, especially in limbs)

• Scoliosis or spinal curvature

• Hypotonia (reduced muscle tone)

Facial and Craniofacial Features

• Prominent forehead (frontal bossing)

• Flat midface or wide-set eyes (hypertelorism)

• Depressed nasal bridge

• Large fontanelles (soft spots on the skull)

Other Potential Features

• Umbilical or inguinal hernias due to connective tissue weakness

• Delayed motor milestones

• Mild developmental delay (in some cases)

• Cryptorchidism (undescended testes in males)

Diagnosis

Due to its extreme rarity and overlapping features with other connective tissue and overgrowth disorders, diagnosing Nevo syndrome requires a thorough clinical evaluation, exclusion of similar conditions, and, when possible, genetic testing.

Diagnostic Steps

• Clinical assessment: A detailed physical examination noting skin, joint, and skeletal anomalies

• Family history: Investigation of consanguinity or similar symptoms in relatives

• Radiographic imaging: To evaluate bone structure, contractures, and spinal alignment

• Skin biopsy: May reveal connective tissue abnormalities under microscopic examination

• Genetic testing: While no specific gene is confirmed, gene panels for connective tissue and overgrowth syndromes may help rule out other disorders

Treatment

There is no cure for Nevo syndrome, and treatment is supportive and focused on symptom management, improving mobility, and preventing complications. A multidisciplinary team approach is essential and may involve pediatricians, orthopedists, geneticists, dermatologists, and physical therapists.

Supportive Care Strategies

• Physical and occupational therapy: To maintain mobility, improve muscle tone, and manage joint hypermobility or contractures

• Orthopedic interventions: May include braces or surgical correction of severe deformities or scoliosis

• Skin care: Measures to protect fragile skin and reduce the risk of bruising and tearing

• Monitoring growth and development: Regular pediatric assessments to track physical and neurological milestones

• Hernia repair surgery: If umbilical or inguinal hernias are present

Psychological and Educational Support

• Special education services for children with developmental delays

• Psychological support for self-esteem and coping with visible physical differences

• Genetic counseling for families to understand inheritance risks and recurrence probabilities

Prognosis

The long-term prognosis of Nevo syndrome remains unclear due to the extremely small number of documented cases. The severity of symptoms can vary significantly among affected individuals. While some children with Nevo syndrome may experience significant orthopedic challenges and developmental delays, others may achieve developmental milestones with early intervention and ongoing support.

The absence of life-threatening organ involvement in most reported cases suggests that life expectancy may be near normal in milder forms, although functional limitations and cosmetic concerns may persist throughout life. Early diagnosis, tailored therapies, and regular follow-up are essential to maximizing independence and quality of life.

As research advances and more cases are documented, greater understanding of the genetic basis and long-term outcomes of Nevo syndrome will become possible, ultimately improving diagnostic and therapeutic strategies.