SOX9 p.Lys106Glu mutation causes acampomelic campomelic dysplasia: Prenatal and postnatal clinical findings

Abstract

We report on a patient with p.Lys106Glu mutation of SOX9 gene causing acampomelic campomelic dysplasia and present comprehensive prenatal and postnatal clinical findings.A 28-year-old primigravida was referred for a first trimester scan at 14 weeks of amenorrhea. The couple was nonconsanguineous and healthy. She had neither a history of prenatal exposure to teratogenic agents nor any family history of congenital malformations. A prenatal ultrasound showed a live fetus with micrognathia, narrow thorax, bilateral renal pyelectasis (3.5 mm), grade 3 echogenic bowel, bowing of tibia and fibula (angulation of the deformity 31 degrees), and talipes equinovarus (Fig. 1A). The crown-rump length was 80.2 cm, the head circumference was 9.98 cm (37th centile), and the femur and humerus measured 1.51 cm (3rd centile) and 1.8 cm (3rd centile), respectively. Nuchal translucency thickness was 0.9 mm. Amniocentesis at 16 weeks of gestation revealed a normal female karyotype. A follow-up ultrasound at 18 weeks unexpectedly demonstrated straight tibia (Fig. 1B). The head circumference of the fetus was 14.48 cm (4th centile), and the femur and humerus measured 2.61 cm (26th centile) and 2.75 cm (66th centile). A 4D ultrasound examination at 21 weeks of gestation further demonstrated micrognathia and low set ears. Proptosis and microstomia were additionally noted at 28 weeks of gestation.After premature rupture of membranes at 38 weeks of gestation, a Caesarean section was performed. The female infant weighed 2,456 g (3rd centile), and had a head circumference of 32 cm (3rd centile), a length of 48 cm (10th centile), and Apgar scores of 6 after 1 min. and 8 after 5 min. The condition of the newborn was severe due to respiratory distress. Immediate continuous positive airway pressure was used during the first 3 hr after birth, and within the next few days the oxygen was provided via nasal cannula. Hypotonia manifested from birth. The phenotype was remarkable for a flat face, low-set ears, shallow orbits, Pierre Robin sequence, microstomia, short neck, small chest, scoliosis, congenital bilateral metatarsus varus deformities, congenital dislocation of the hips, clitoromegaly, and tracheobronchomalacia. Radiological findings included scoliosis and kyphosis of the thoracic spine, 11 pairs of ribs, abnormal cervical vertebral bodies, dysplasia of thoracic vertebrae, and no overt bending of the long bones (Fig. 1C). Further investigation such as brain and cervical spine MRI, echocardiography, and renal and abdominal ultrasound examination showed no significant abnormalities. For the correction of clubfeet, plaster casts were applied. Dislocation of the hips was treated with the Frejka pillow. The neonatal period was complicated by feeding problems and poor weight gain. Tube feeding could be terminated 1 month after birth. The girl had a few complicated respiratory infections. During the evaluation at the age of 6 months, the head circumference was 42 cm (25th centile), her weight was 4,520 g (<3rd centile), and her length was 60 cm (<3rd ...

A mutation creating an upstream initiation codon in theSOX95′UTRcauses acampomelic campomelic dysplasia

“…The other report summarizes chromosomal rearrangements upstream and downstream of SOX9, with 13 and nine rearrangements reported for ACD and CD cases, respectively (Table 1; Fonseca et al 2013). Three additional ACD mutations have meanwhile been published, two missense mutations (Gopakumar et al 2014;Preiksaitiene et al 2016) and one translocation (Walters-Sen et al 2014). Despite this large number of reported SOX9 mutations in ACD, the functional consequences of these mutations have only occasionally been tested experimentally.…”

Genomo persitvarkymai, esant įgimtiems centrinės nervų sistemos raidos sutrikimams: kilmė, genominiai mechanizmai, funkcinės ir klinikinės pasekmės. Darbų apžvalga

“…Re tai ner vi nio vamz de lio de fek tus le mia struk tû ri niai chro mo so mi niai per si tvar ky mai. Nu sta ty tuo se chro mo so mi niuo se po kyèiuo se esan èiø kad he ri no ge nø (CDH6, CDH9, CDH10, CDH12, CDH18) ir BCHE, TNIK, SOX2, MAP6D1 bei DVL ge nø raið ka yra di de lë emb rio no ir vai siaus CNS, todël ne ga li ma at mes ti ðiø ge nø do zës po ky èio áta kos CNS rai dos su tri ki mui [15,16].…”

“…sa vaitës, ta èiau vë liau ma to mi tie sûs ga lû niø kau lai. Pra nykstan èios kam po me li jos vaiz das ga li bû ti svar bus ul tra gar sinis griau èiø dis pla zi jos po þy mis pre na ta li niu lai ko tar piu [15].…”

Campomelic dysplasia with dextrocardia and without sex-reversal

“…Repeated prenatal ultrasound examinations could identify additional signs that allow a differential diagnosis with other skeletal dysplasia [9,10].…”