Thanatophoric dysplasia (type 2): A rare detection on antenatal ultrasound

A 25-year-old primigravida patient with complaints of 5 month amenorrhea was referred to our centre for antenatal ultrasound examination to rule out Twin pregnancy as uterine fundal height was more than the expected gestational age of 20 weeks.

Antenatal Ultrasound findings revealed clover-shaped deformity of skull ( Fig. 1) resulting from premature closure of sagittal, coronal & lambdoid sutures, thus trilobed protrusion of skull was noted. Abdominal circumference was corresponding to  30 weeks 5 days ( Fig. 2). However, all long bones including Humerus, Radius, Ulna, Femur, Tibia, Fibula were corresponding between 15 to 18 weeks.( Fig. 3 (a),( b),(c))  Both upper &  lower limbs were short & stubby  ( Fig. 4)with narrow thorax. Amniotic liquor was found to be increased ( Amniotic fluid index ~30 cms). Fetal Spine was normal. So, on the basis of ultrasonography findings, diagnosis of Type 2 Thanatophoric Dysplasia was made. Patient opted for immediate termination of pregnancy. Clinical Photographs of the fetus were also taken  after delivery of fetus which revealed clover-shaped deformity of skull, narrow chest, short & stubby limbs. ( Fig. 5)

Thanatophoric Dysplasia is congenital most lethal form of skeletal dysplasia followed by Osteogenesis imperfecta type II. The term “Thanatophoric” derives from a Greek word for  “Death bringing” or “ Death Bearing”. Thanatophoric dysplasia is a rare congenital entity affecting fetus in utero and is characterised by marked underdevelopment of fetal skeleton & short limb dwarfism[1] with a estimated incidence rate of about 1 in every 20000 to 50000 [2].

Thanatophoric Dysplasia is caused by de novo autosomal dominant mutations in the Fibroblast Growth Factor Receptor 3 ( FGFR 3 ) gene located on Chromosome band 4p 16.3 [3,4,5]. The basic proposed pathogenesis is persistence of abnormal fetal mesenchymal tissue causing disorganised enchondral bone formation which transforms to abnormal bone & cartilage [6]. Two types of Thanatophoric dysplasia have been recognized; type I (80%) constitutes fetus with more shortened curved limbs giving telephone receiver appearance with macrocephaly but normal shaped skull while type II (20%) is associated with Clover shaped deformity of skull with straight shortened limbs.

Diagnosis is, often, made by antenatal ultrasound done in second or third trimester which includes following imaging features like – clover shaped deformity of skull or macrocephaly, short or curved long bones especially femur, narrow thorax with short , splayed ribs, redundant soft tissue of upper & lower limbs and polyhydramnios. High-resolution 3D/ 4D ultrasound can reveal cranio- facial abnormalities & skin thickening more precisely.

Most of the fetus with this disorder die in utero thus, carries very poor prognosis as death mostly occurs due to  brainstem compression from narrowed foramen magnum or due to respiratory failure owing to hypoplastic lungs [7]. Prenatal diagnosis can also be confirmed by molecular analysis of mutation in FGFR 3 gene extracted from fetal cells obtained by chorionic villous sampling at 10 to 12 weeks or by amniocentasis at 15 to 18 weeks.

Meticulous Antenatal Ultrasound examination helps in precise timely detection of this rare entity of skeletal dysplasia. Since this entity carries  very poor prognosis, so couples can be counselled regarding early termination of pregnancy.