What are the causes and recommended work‑up for premature greying of hair in children?

Causes of Premature Grey Hair in Children

Premature greying in children requires systematic evaluation for genetic syndromes (particularly TERT/TERC mutations), nutritional deficiencies (vitamin D3, B12, ferritin, calcium), and thyroid dysfunction, as these represent the most clinically significant and treatable causes.

Genetic and Syndromic Causes

TERT/TERC mutations are the most critical genetic cause to identify, as affected children present with premature graying alongside nail and skin changes, sensorineural deafness, cirrhosis, hereditary pulmonary fibrosis, emphysema, and signs of early aging 1. These patients face substantially increased risk for head and neck cancers, anogenital cancers, and skin cancer, making early identification essential for cancer surveillance 1, 2.

Additional genetic syndromes associated with premature greying include:

• Fanconi anemia and dyskeratosis congenita (FANC genes): Present with dysmorphic features, short stature, nail and skin changes, thumb hypoplasia, and pulmonary fibrosis 1
• Autosomal dominant inheritance patterns are most common in familial cases without syndromic features 3, 4

Nutritional Deficiencies

Vitamin D3 deficiency shows the strongest association with premature greying in children. A case-control study demonstrated significantly higher rates of vitamin D3 deficiency and insufficiency in children with premature greying compared to controls 3. Additional nutritional deficiencies include:

• Serum ferritin: Low levels correlate with premature greying 3
• Serum calcium: Deficiency identified in affected children 3
• Vitamin B12: Deficiency associated with premature greying 3, 4

Autoimmune and Endocrine Disorders

Thyroid dysfunction is a critical treatable cause that must be evaluated in all children with premature greying 1, 2. Thyroid disease directly affects hair pigmentation mechanisms 1.

Autoimmune associations include:

• Vitiligo: Frequently coexists with premature greying 5
• Atopic conditions: Show increased association 4
• Other autoimmune disorders: Various conditions linked to premature greying 3, 4

Environmental and Oxidative Stress Factors

Oxidative stress plays a central pathophysiological role in premature greying through melanocyte dysfunction 6, 7, 4. Contributing factors include:

• Smoking exposure: Accelerates greying process 7
• Dietary factors: Poor nutrition contributes to oxidative damage 7
• Environmental stressors: Cumulative oxidative burden 7

Recommended Diagnostic Work-Up

Obtain the following laboratory tests in all children with premature greying 2, 3:

1. Complete blood count with hemoglobin
2. Serum ferritin
3. Vitamin B12 level
4. Vitamin D3 (25-hydroxyvitamin D)
5. Serum calcium
6. Thyroid function tests (TSH, free T4, anti-thyroglobulin antibodies) 1, 2

Consider genetic testing for TERT/TERC mutations when premature greying occurs with 2:

• Nail and skin changes
• Sensorineural hearing loss
• Family history of early-onset cancers
• Signs of premature aging
• Pulmonary or hepatic symptoms

Clinical Pitfalls to Avoid

• Do not dismiss premature greying as purely cosmetic without excluding syndromic causes, particularly TERT/TERC mutations that require cancer surveillance 1, 2
• Do not overlook nutritional deficiencies, as vitamin D3, ferritin, calcium, and B12 deficiencies are treatable causes 3
• Do not skip thyroid function testing, as thyroid dysfunction is a reversible cause of premature greying 1, 2
• Do not ignore family history, as autosomal dominant inheritance is common 3, 4

Treatment Approach

Address identified nutritional deficiencies with appropriate supplementation 3, 4. For vitamin D deficiency, follow general international recommendations for age-appropriate dosing, with maintenance therapy due to chronicity 1.

Treat underlying thyroid dysfunction when identified 1, 2.

Hair dyes remain the primary cosmetic treatment after nutritional supplementation and treatment of underlying conditions 4.