Oto-onycho-peroneal syndrome: Further delineation and first fetal report
Abstract
We report on the sixth case and first fetal description of oto-onycho-peroneal syndrome (MIM 259780). This entity consists in the association of ear anomalies (-oto), hypoplastic nails (-onycho), hypoplastic or absent fibulae (-peroneal), and shoulder anomalies. Described for the first time by Leiba et al. [1975: Birth Defects 11:67–73] in a male patient, coined by Pfeiffer [1982: Eur J Pediatr 138:317–320], and confirmed by Devriendt et al. [1998: J Med Genet 35:508–509] this condition is most likely autosomal recessive, given the occurrence in sibs of both sexes with normal parents. © 2004 Wiley-Liss, Inc.
INTRODUCTION
Leiba et al. [1975] reported for the first time on a male patient, product of a consanguineous couple, presenting a distinctive association of ear anomalies, nail hypoplasia, broad toes, bilateral deformation of the lateral part of the clavicles and acromions, enlargement of the phallus with hypospadias, and other minor skeletal anomalies.
Oto-Onycho-Peroneal syndrome was coined by Pfeiffer [1982] describing two sibs presenting an association of abnormal ears, hypoplastic nails, and skeletal anomalies such as hypoplastic fibulae and straight claviculae.
The syndrome was confirmed by Devriendt et al. [1998] in two sibs who shared similar features including abnormal external ears, nail hypoplasia, and skeletal anomalies with fibrous fusion between the distal third of the clavicle and the spine of scapula.
This condition is most likely autosomal recessive, given the occurrence in sibs of both sexes with normal parents, as in the case reported by Leiba et al. [1975], and also described in a consanguineous family [Devriendt et al., 1998].
We report on the first diagnosis of Oto-Onycho-Peroneal syndrome in a 17-week fetus.
CLINICAL REPORT
Clinical History and Ultrasound Findings
A 29-year-old primigravid woman was seen for a routine ultrasound scan at 15 weeks of gestation. She and her 29-year-old partner were not consanguineous, and there was no noteworthy family history. The scan showed: nuchal thickening (4.6 mm), micrognathia, and multiple limb anomalies. The second and third digits were bilaterally widely spaced, the thumbs were thick and abducted with only first phalanx identified. There was contracture of abnormally shaped lower limbs with only one bone present in each leg.
Amniotic fluid sampling showed a normal male karyotype: 46,XY.
The parents opted for termination of pregnancy at 17 weeks' gestation.
Pathologic Findings
The male fetus (weight = 140 g, crown rump distance = 13 cm, foot length = 22 mm, head circumference = 13 cm) (Fig. 1) was rather small for 17 weeks' gestation. He presented multiple anomalies. Dysmorphic facial features included low set ears with prominent anti-tragus and unfolded helices. The left ear was rotated and pointed, the right one was rather large with hypoplastic lobule (Fig. 2). The face was flat, with large nose, large columella, and flat philtrum (Fig. 3). In addition, microretrognathia, down slanting palpebral fissures, and nuchal oedema were noted.
A male fetus showing limb contractures, hand, and feet anomalies. [Color figure can be viewed in the online issue, which is available at www.interscience.wiley.com.]
Hypoplastic right ear with unfolded helices, and prominent antitragus. [Color figure can be viewed in the online issue, which is available at www.interscience.wiley.com.]
Dysmorphic facial features including large nose, large columella, and flat philtrum. [Color figure can be viewed in the online issue, which is available at www.interscience.wiley.com.]
The upper limbs presented elbow pterygia (Fig. 4). The digits, particularly the thumbs, appeared stubby with the tip edema associated with hypertrophic skin folds. There was a nail aplasia on the thumbs, and hypoplasia on the other fingers (Fig. 5). Thumb and index were abnormally spaced with stiff interphalangeal joints. In addition, clinodactyly of the other fingers was noted.
Elbow pterigia. [Color figure can be viewed in the online issue, which is available at www.interscience.wiley.com.]
Finger anomalies with stubby digits with enlarged tips, and nail hypoplasia. [Color figure can be viewed in the online issue, which is available at www.interscience.wiley.com.]
The lower limbs exhibited knee contractures, and short, abnormally shaped legs, with severe talipes equinovarus. The toes I/II/III were broadly spaced with enlargement of the tips, and nail hypoplasia (Fig. 6). The great toes were hypoplastic resembling the second toes.
Feet with widely spaced toes, broad tips, and nail hypoplasia. [Color figure can be viewed in the online issue, which is available at www.interscience.wiley.com.]
Internal organ examination was normal except for the right kidney presenting microcystic changes.
Histologic examination confirmed a hypo-dysplastic changes in the right kidney with occasional tubular cystic dilatations. In addition, focal adrenal cytomegaly was noted.
Brain, eyes, and spinal cord were normal for the age.
X-rays revealed bilateral fusion between the distal third of the clavicle and the spine of the scapula (Fig. 7). Bilateral aplasia of the fibulae was confirmed. The tibiae were bowed. The head of radius and ulna were abnormally spaced. First sacral vertebral body was irregularly shaped, and the iliac wings were flared with an incurved lower part. The metatarsus and metacarpus were fan-shaped. In addition, there was hypoplasia of the middle phalanx of the index finger and aplasia of the middle phalanx of the fifth finger. Thin first metatarsals resembling the second ones were noted (Fig. 8).
X-rays of acromioclavicular fusion. [Color figure can be viewed in the online issue, which is available at www.interscience.wiley.com.]
X-rays of the body, note absent fibulae. [Color figure can be viewed in the online issue, which is available at www.interscience.wiley.com.]
DISCUSSION
We report the sixth case of Oto-Onycho-Peroneal syndrome, and the first fetal description of the syndrome. The present fetus exhibits the most severe phenotype of Oto-Onycho-Peroneal group spectrum hitherto reported. In addition to ear, finger, nail, fibular, and shoulder anomalies, he presents early contractures with pterygia, severe talipes equinovarus, other skeletal malformations, as well as renal anomaly.
Hypoplastic ears and nails seem to be a constant feature of the syndrome (5/5 patients reported), contrasting with fibular anomalies which are present in only 2/5 patients reported. Shoulder anomalies with straight claviculae and/or acromio-clavicular fusion seem to be one of the hallmark of the syndrome, present in 5/5 of the reported patients. Our fetus presents both fibular agenesis, and acromio-clavicular fusion. Thus, we suggest calling this entity oto-onycho-acromio-clavicular syndrome might be more appropriate in order to include patients with a milder spectrum of anomalies.
This new report of Oto-Onycho-Peroneal syndrome corroborates that this disorder represents a rare entity, detectable in utero by routine ultrasound examination. Fetopathological examination may identify this most likely autosomal recessive syndrome on the characteristic shoulder, ear, and nail anomalies.
