White Streak of Hair: A Thread to an Unusual Diagnosis in a Mother-Infant Dyad

Born to a 35-year-old primigravida woman with benign prenatal screensNonconsanguineous couple, spontaneous conceptionNormal fetal surveyAppropriate fetal growthEstimated gestational age: 37 weeksSpontaneous vaginal deliveryApgar score: 8 and 9 at 1 and 5 minutes, respectivelyHeart rate: 140 beats per minuteRespiratory rate: 46 breaths per minuteBlood pressure: 60/42, mean 48 mm HgOxygen saturation: 95% (in room air)Temperature: 98.6 °F (36.5 °C)Birth weight 2600 g (fifth percentile as per World Health Organization [WHO] chart), birth length 48 cm (sixteenth percentile as per WHO chart), and head circumference 33 cm (twelfth percentile as WHO chart)Head: normocephalic; normal, open, flat fontanelles; white forelock of hair occupying a small area is seen above the infant’s forehead (Figure 1). This section of hair is uniformly depigmented with surrounding hair showing normal pigmentation; and multiple 5–10 mm hypopigmented patches in the surrounding scalp (including the midline forehead).Face: broad nasal bridge, normal eye examination, and nasal cavityOral cavity: pink mucosae, intact palate, and normal sucking and rooting reflexLungs: clear, equal breath sounds; no respiratory distressCardiovascular: normal first heart sound and second sound; regular rate and rhythm; no murmurs or gallopsAbdomen: soft and nontender; normal bowel sounds; no hepatosplenomegalyGenitourinary: normal term male genitalia; patent anusSkeletal: spine appears normalSkin: no icterus, birthmarksNeurologic: symmetric Moro reflex; normal strength and toneFIGURE 1.White forelock of hair in (A) infant and (B) mother, obtained with permission.Waardenburg syndromeBrachio-oculo-facial syndrome (BOFS)Deaf-blind hypopigmentation syndromeDyskeratosis congenitaPartial albinismEvaluation of the mother shows a white forelock with depigmented hair with a 10 × 7 cm hypopogimented patch of skin over the forehead (Figure 1). After discussion with the mother, the team learned that these findings were present since birth, and both the white forelock and skin hypopigmentation gradually increased in size. The mother also has symmetric hypopigmented patches over the upper and lower limbs with areas of pigmented skin in between. A 3 × 4 cm patch of depigmentation is also seen over her abdomen. She has not been evaluated previously for these findings. The mother did not consent to a biopsy of her skin or an audiologic evaluation of herself. Examination of the father is negative for Waardenburg syndrome.The infant-mother dyad is evaluated by a multidisciplinary team involving a neonatologist, dermatologist, ophthalmologist, genetics specialist, and audiologist. The infant has a brainstem-evoked response audiometry that is normal. A hair mount examination of the infant’s depigmented hair shows uniform hypopigmentation with absent melanin pigment, whereas the surrounding hair shows appropriate pigmentation (Figure 2). The findings of piebaldism (ie, white forelock of hair) and multiple hypopigmented patches over the torso are most consistent with a clinical diagnosis of type I Waardenburg syndrome.The neonate is also examined for the presence of other neuronal migration disorders. He does not have any evidence of feeding intolerance, and he is passing stool appropriately, ruling out Hirschsprung disease associated with Waardenburg syndrome. A detailed ophthalmologic examination and genetics consultation are obtained, and no additional abnormalities such as cataracts and skeletal deformities are found.The neonate tolerates exclusive breastfeeding and remains hemodynamically stable. He is discharged home at 7 days of age. He is currently 3 months old with normal growth and age-appropriate neurodevelopment. His parents are counseled about Waardenburg syndrome and the need for genetic assessment of the infant-mother dyad, which they have currently deferred given financial constraints. He is being followed by genetics, dermatology, and audiology.Waardenburg syndrome in the mother-infant dyadWaardenburg syndrome is a group of genetic conditions with an autosomal dominant pattern of inheritance that is characterized by abnormal distribution of melanocytes resulting in patchy depigmentation. The incidence of patients affected with this syndrome is reported to be approximately 1/42 000 globally.1 There are 4 clinical variants of Waardenburg syndrome (Table 1) with type 1 and type 2 being the most common. Types 1 and 3 are due to mutations in the paired box 3 gene.To establish a clinical diagnosis of type 1 Waardenburg syndrome, 2 major or 1 major and 2 minor criteria are needed; these criteria2 are listed in Table 2. One major criterion is a white forelock, which refers to a triangular depigmented region of white hairs located in the anterior midline of the scalp. The infant in this case is diagnosed with type 1 Waardenburg syndrome because he has 2 major criteria (white forelock and first-degree relative with Waardenburg syndrome) and 1 minor criteria (broad nasal bridge). The characteristic histopathologic finding of Waardenburg syndrome is the absence of melanocytes involving the skin, hair, and/or eyes. Dihydroxyphenylalanine-positive melanocytes are lacking as a result of mutations that affect the function of the neural crest involved in the formation of melanocytes.3At present, Waardenburg syndrome has no definitive treatment. However, the life expectancy in children with Waardenburg syndrome is normal.4 In patients with this syndrome, early diagnosis, detection, and timely treatment of hearing abnormalities and management of dermatologic manifestations are important for normal neurobehavioral development and better quality of life. Sun protection is essential because of the increased risk of phototoxicity. For those with sensorineural hearing loss, the definitive surgical treatment available is cochlear implantation.5 Affected adults should be counseled regarding recurrence based on type and the importance of antenatal genetic testing for better parenteral preparedness and anticipation.BOFS was ruled out based on the absence of branchial anomalies, including supra-auricular sinuses, cervical skin lesions, and external ear and ocular abnormalities.6 The absence of hearing loss, ocular abnormalities, and hypopigmented lesions in other parts of the body decreased the likelihood of deaf-blind hypopigmentation.7 Dyskeratosis congenita is characterized by bone marrow failure syndrome, abnormal nails, reticular skin pigmentation, and oral leukoplakia, which were absent in the index case.8 Patients with partial albinism have large pigment collections in hair shafts and an abundance of mature melanosomes in their melanocytes.9 The hair mount of the index neonate did not have these features, ruling out this condition.A white forelock of hair in a neonate is a rare manifestation and indicates an underlying systemic illness.Detailed clinical examination of the parent of an infant with a white forelock helps in establishing a clinical diagnosis, especially in those with neonatal presentation.Audiologic, ophthalmologic, and genetic evaluation of neonates with Waardenburg syndrome in the neonatal period aids in better parenteral preparation and improvement in the quality of life.American Board Of Pediatrics Neonatal-Perinatal Content SpecificationRecognize common chromosome deletion or insertion syndromes presenting in the neonatal periodUnderstand common inheritance patterns of genetic diseaseThe authors thank Dr Sangeeta Ravat, Dean of Seth Gordhandas Sunderdas Medical College, and King Edward Memorial Hospital in Mumbai for granting permission for publication.