A term female presents with abnormal facies.
22-year-old gravida 1 para 0 Caucasian mother who has congenital deafness and the following phenotype
Blood type O+, antibody screen negative, hepatitis B surface antigen negative, rubella immune, rapid plasma reagin nonreactive, group B Streptococcus screen negative
Birth History and Presentation
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.
Heart rate, 160 beats/min
Respiratory rate, 48 breaths/min
Blood pressure, 67/32 mm Hg
Temperature, 98.1°F (36.7°C)
Lateral displacement of the medial canthi with short palpebral fissures, broad and high nasal bridge with hypoplastic alae nasi, white forelock view photo
Lungs: Clear; equal breath sounds without retractions
Cardiovascular Examination: Normal S1, S2; regular rhythm; no murmur; equal peripheral pulses
Abdominal Examination: Soft and nontender; liver palpable 2 cm below the right costal margin; three vessels in the umbilical cord
Genitourinary Examination: Normal female; patent anus
Extremities: Normal; hips stable
Neurologic Examination: Appropriate strength and tone
Skin: No rashes or lesions; nonicteric
The infant failed the newborn hearing screen bilaterally.
Lateral Displacement of the Inner Canthi*
Inner canthal fold, lateral displacement of inner canthi, ptosis
Branchial defects, lacrimal duct obstruction, pseudocleft of upper lip
Acrocephaly, polydactyly and syndactyly of feet, lateral displacement of inner canthi
Primary defect of the fourth branchial arch and the derivatives of the third and fourth pharyngeal pouches
Peculiar facies, infantile eczema, small stature, mild microcephaly
Fetal Valproate Syndrome
Epicanthal folds, telecathus, cardiovascular defects, limb abnormalities, neural tube defects
Masklike facies, pursed lips, hypoplastic alae nasi, talipes equinovarus
Frontonasal Dysplasia Sequence
Primary defect in midfacial development, with incomplete anterior appositional alignment of eyes
Cleft tongue, conductive hearing loss, partial reduplication of hallux
Oral frenula and clefts, hypoplasia of alae nasi, digital asymmetry
Oromandibluar-Limb Hypogenesis Spectrum
Lateral displacement of the medial canthi, partial albinism, deafness
X-Linked Alpha-Thalassemia/Mental Retardation (ATR-X) Syndrome
Severe mental retardation, telecanthus, microcephaly, genital abnormalities
*Adapted from Jones KL, ed. Smith's Recognizable Patterns of Human Malformation. 5th ed. Philadelphia, Pa: WB Saunders Co; 1997.
Waardenburg Syndrome Type I
Diagnosed clinically according to the Waardenburg Consortium.
History of Waardenburg Syndrome
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.
Type I WS is characterized by full symptomatology of the disease:
Dystopia canthorum (99%)
Hypoplasia of the nasal bone, short philtrum, retropositioned maxilla
Convergent strabismus, reduced visibility of the medial sclera
Broad nasal root (80%)
Heterochromia iridium (25%)
Congenital deafness (25%)
White forelock (45%)
Type II WS is a heterogeneous group that does not include dystopia canthorum; white forelock and hypopigmentary skin lesions are also less common:
Sensorineural hearing loss (77%)
Heterochromia iridium (50%)
Type III WS is also referred to as Klein-Waardenburg syndrome. Type III WS is most similar to Type I (presenting with the full spectrum of symptomatology), but includes additional musculoskeletal anomalies:
Aplasia of the first two ribs
Cystic formation of the sacrum
Type IV WS is also known as Shah-Waardenburg syndrome and describes the association of WS with congenital aganglionic megacolon (Hirschsprung disease).
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:
Congenital sensorineural hearing loss
Pigmentation abnormalities of the iris
Dystopia canthorum=W index greater than 1.95.
The measurements necessary to calculate the W index in mm are: inner canthal distance (a), interpupillary distance (b), and outer canthal distance (c)
Broad/high nasal root
Hypoplastic alae nasi
Premature grey hair (before age 30 years)
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.
- Copyright © 2006 by the American Academy of Pediatrics
- Jones KL
- Read AP,
- Newton VE