A Term Newborn Who Has Abnormal Facies

Abstract

A term female presents with abnormal facies.The infant was delivered by the vaginal route in vertex presentation. She made the transition to the extrauterine environment without difficulty, with Apgar scores of 9 at both 1 and 5 minutes. Her birthweight was 3.3kg, which was appropriate for gestational age.The infant failed the newborn hearing screen bilaterally.*Adapted from Jones KL, ed. Smith's Recognizable Patterns of Human Malformation. 5th ed. Philadelphia, Pa: WB Saunders Co; 1997.Diagnosed clinically according to the Waardenburg Consortium.Waardenburg syndrome (WS) is an autosomal dominant disorder characterized by varying degrees of hypopigmentation, hearing loss, and defects in neural crest cell migration. The syndrome was named in 1951 by Petrus Johannes Waardenburg, a Dutch optometrist, who first defined the syndrome with six primary elements, including lateral displacement of the inner canthi with blepharophimosis, prominent broad nasal root, hypertrichosis of the medial eyebrows (synophyrys), white forelock, heterchromia iridis, and deafness. The frequency of WS is estimated to be 1 in 200,000 in the general population of the Netherlands and 1 in 20,000 in Kenya. There is no race or sex predilection, despite these reported frequencies.Multiple terms are used to describe the abnormal ocular findings in WS. Lateral displacement of the inner canthi gives rise to short palpebral fissures, resulting in telecanthus. Telecanthus is defined as an increased distance between canthi and is synonymous with hypertelorism (increased distance between two organs). Dystopia refers to the abnormal position of part of an organ and frequently is used to describe the position of the eyes in WS (ie, dystopia canthorum). Blepharophimosis is defined as a decrease in the size of the palpebral aperture without fusion of the lid margins, which results in convergent strabismus.Infants who have WS can be identified soon after birth. Four types of WS have been described, and all forms demonstrate marked variability, even within families.Congenital deafness in WS can be bilateral or unilateral and severe or moderate. Patients who have hearing loss and WS have temporal bone anomalies, with 50% having enlargement of the vestibular aqueduct visible on computed tomography.Cutaneous abnormalities include both hypopigmented lesions and hyperpigmented lesions and can resemble the lesions found in piebaldism, tuberous sclerosis, and neurofibromatosis.Ocular color abnormalities of WS present in three patterns: heterochromia iridis, bilateral isohypochromia iridis (pale blue eyes), and hypopigmentation of the fundus.Syndromes that have similar clinical features include Rozycki syndrome (deafness and viteligo), Fisch syndrome (congenital deafness and early graying of the hair), and Woolf syndrome (albinism and deafness).According to the Waardenburg Consortium, an individual can be diagnosed if two of the following major criteria or one major and two minor criteria are present:The measurements necessary to calculate the W index in mm are: inner canthal distance (a), interpupillary distance (b), and outer canthal distance (c)WS is associated with neural crest-derived melanocyte deficiency caused by mutations in transcription factors. More than 90% of individuals who meet the clinical diagnostic criteria for WS Type I have mutations in the PAX3 gene. The PAX3 gene is located on chromosome 2 and controls some aspects of the development of the face and inner ear. Approximately 15% of individuals who have Type II WS are heterozygous for mutations in the microphthalmia-associated transcription factor (MITF) gene. The MITF gene is found on chromosome 3 and is involved in the development of the ear. Type III WS is considered an extreme presentation of Type I, with some affected individuals being homozygous for the PAX3 gene mutation. Type IV WS can be caused by mutations in the genes for endothelin-3 or one of its receptors, EDNRB and EDN3 genes.