Prenatal transient alveolomaxillary defect in a case of mucolipidosis II (I‐cell disease)

Abstract

Mucolipidosis II (ML II or I-cell disease) is a rare inherited lysosomal storage disease that causes multisystem deterioration and death in early childhood. Little is known about the fetal features of this condition, and therefore the diagnosis is usually established postnatally when core symptoms occur, including severe growth/developmental delay, coarse facial features, multiplex skeletal deformities and joint limitation1. We report a case of ML II which presented an uncommon fetal sign of transient alveolomaxillary defect (TAD) on prenatal ultrasound imaging before 28 weeks' gestation. A 23-year-old Taiwanese primigravida was referred to our clinic for evaluation of fetal cleft lip/palate suspected on ultrasound examination at 24 weeks' gestation. Detailed sonographic examination confirmed the presence of an alveolomaxillary defect, in which a hole in the maxilla was identified but the soft tissue of the upper lip appeared intact (Figure 1). No other associated structural abnormality was noted. Chromosome analysis revealed a normal male karyotype. The mother denied any drug or teratogen exposure and the personal and family histories of both parents were unremarkable. The pregnancy was then followed with normal serial ultrasound examinations. Unexpectedly, the alveolomaxillary defect was no longer present in the repeat scans performed at 28 weeks' gestation and thereafter. The etiology of the TAD thus remained unknown during the prenatal period. Prenatal ultrasound image at 24 weeks' gestation showing the alveolomaxillary defect presenting as a hole (arrow) while the upper lip seems intact. The infant was born with a weight of 2105 g (10th percentile) via vaginal delivery at 37 weeks' gestation. No facial clefting was noted after birth. Magnetic resonance imaging and computed tomography revealed the craniofacial/maxillary structure to be normal (Figure 2). Cranial sonography presented no findings except mild left ventriculomegaly. Other features of the neonate included a left paramedian caruncle in the upper lip, light hair color, lax skin with sparse subcutaneous fat, long digits and bilateral inguinal hernia. At 2 months of age the infant presented with coarse facial features and dysostosis multiplex (generalized osteopenia, atlas hypoplasia, short, thick clavicles, thick elevated scapula with poorly formed glenoid fossa, oar-shaped ribs and lumbosacral spine). Lysosomal enzyme evaluation and molecular analysis confirmed the diagnosis of ML II. There was markedly increased lysosomal enzyme activity in the plasma and the infant was found to be compound heterozygous with two truncated mutations, c.2422delC (p.L808fsX19) and c.3565C > T (p.R1189X), in the disease-causing gene GNPTAB. The infant died of respiratory failure at the age of 14 months. The family declined necropsy and biopsy of the baby, precluding histopathological investigation of the alveolomaxillary region. Postnatal images of the patient at 14 days (a–c) and at 2 months (d,e) of age. Photographs show the following clinical features: (a) a left paramedian caruncle in the upper lip (arrowhead), light hair color, lax skin with sparse subcutaneous fat, (b) long fingers and (c) long toes. Magnetic resonance imaging (d) and computed tomography (e) examinations showed the alveolomaxillary structure to be normal. TAD is an extremely rare condition in fetuses. To our knowledge, the association of the sign with fetal ML II has not previously been reported, but maxillofacial lesions have been occasionally found in children with ML II2, 3. Some of the lesions found in affected children are surrounded by impacted tissue, and it has been suggested that this involves a process in which the bony defect is replaced with abnormal connective tissue3. Indeed, recent studies have shown that ML II can lead to abnormalities in connective tissues with frequent skeletal involvement4-6. Maxillary deformation followed by tissue replacement associated with ML II may account for the TAD seen in our patient. The possible association of TAD and fetal ML II may provide useful information for prenatal diagnosis and counseling; that is, even a transient bony defect may imply an underlying inherited metabolic condition such as lysosomal storage disease. M. Chen* ** §§, Y.-Y. Ke* §, S.-P. Chang*, D.-J. Lee , C.-H. Chen¶, G.-C. Ma* ¶¶, * Department of Genomic Medicine, Erlin branch, Changhua, Taiwan, Department of Medical Research, Erlin branch, Changhua, Taiwan, Department of Obstetrics and Gynecology, Erlin branch, Changhua, Taiwan, § Department of Pediatrics, Changhua Christian Hospital, Erlin branch, Changhua, Taiwan, ¶ Department of Obstetrics and Gynecology, Changhua Christian Hospital, Erlin branch, Changhua, Taiwan, ** Department of Obstetrics and Gynecology, College of Medicine and Hospital, National Taiwan University, Taipei, Taiwan, Department of Medical Genetics, College of Medicine and Hospital, National Taiwan University, Taipei, Taiwan, Department of Life Sciences, National Chung-Hsing University, Taiwan, §§ Department of Life Sciences, Tunghai University, Taiwan, ¶¶ Institute of Biochemistry and Biotechnology, Chung Shan Medical University, Taichung, Taiwan