Case of the Week #599
(1) Department of Genetics, Polish Mother's Memorial Hospital, Lodz, Poland; 2 - Medical Genetics Department - Institute of Mother and Child, Warsaw, Poland; (2) Kasr Al Ainy teaching hospital, Egypt
A 35-year-old multipara with non-contributory medical history presented at 20 weeks +4 days based on early scan. Ultrasound revealed the following findings. There were other numerous abnormalities in the rest of the scan apart from the ones shown here.
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Answer
We present a case of Thanatophoric Dysplasia with abnormal sulcation in the temporal lobes.
Discussion
Thanatophoric dysplasia is a skeletal dysplasia characterized by severe micromelia, short ribs and pulmonary hypoplasia. It is nearly always lethal in the neonatal period due to respiratory failure [1]. It has a prevalence of 0.21 to 0.80 per 10,000 births [2]. Thanatophoric dysplasia is usually caused by a de novo mutation of fibroblast growth factor receptor 3 gene (FGFR3) on chromosome 4, which results in constitutive activation of the FGFR3 tyrosine kinase [1,3]. Thanatophoric dysplasia is divided into two subtypes: type 1 features bowed/bent femurs and metaphyseal flaring, resulting in a characteristic ‘telephone receiver’ appearance. Type 2 is characterized by straight femurs and a ‘cloverleaf’ skull, though this finding may also appear in type 1 [1,3].
In addition to the skeletal defects, fetuses with thanatophoric dysplasia demonstrate characteristic central nervous system findings. Temporal lobe abnormalities were first dscribed in thanatophoric dysplasia in 1971, and include deep transverse sulci across the infero-medial temporal surface, as well as temporal lobe enlargement, especially along the medial-lateral axis resulting in a globular appearance of the brain [4]. This is in contrast to the surface of a normal 18 to 22 week fetal brain which is essentially smooth. Additional central nervous system findings include megalencephaly, hippocampal dysplasia, rudimentary dentate gyrus, and polymicrogyria [4].
Temporal lobe dysplasia in cases of short-limb skeletal dysplasia is considered virtually pathognomonic for thanatophoric dysplasia, and can be identified on prenatal ultrasound and MRI between 19 to 21 weeks of gestation [1,3]. The routine axial biparietal diameter plane cuts through the cavum septi pellucidi and the cerebral peduncles, above the cerebellum and the inferior portion of the temporal lobe where the abnormal sulcation is most apparent. Therefore, abnormal gyration of the temporal lobes may be overlooked in this plane. Obtaining an axial image just inferior to the biparietal diameter plane, which roughly includes the orbits and brainstem/midbrain, or a coronal image that includes the cerebellum or midbrain better visualizes the temporal lobe dysplasia [2,3]. Using these modified planes, the abnormal deep medial temporal sulcation can be visualized as early as 16 weeks gestation [2].
In conclusion, the combination of short limbs, narrow chest, macrocephaly, and temporal lobe dysplasia may be a pathognomonic sonographic sign for thanatophoric dysplasia in mid-trimester fetuses. Sequencing of the FGFR3 gene, which is more affordable than whole genome sequencing, should be considered when these findings are identified on ultrasound or MRI. Awareness of these brain malformations in thanatophoric dysplasia can improve prenatal diagnostic accuracy and can aid in patient counseling.
References
[1] Fink AM, Hingston T, Sampson A, Jessica Ng, Palma-Dias R. Malformation of the fetal brain in thanatophoric dysplasia: US and MRI findings. Pediatr Radiol 2010; 40: S134-S137.
[2] Wang DC, Shannon P, Toi A, Chitayat D, Mohan U, Barkova E, et al. Temporal lobe dysplasia: a characteristic sonographic finding in thanatophoric dysplasia. Ultrasound obstet Gynecol 2014; 44: 588-594.
[3] Blaas H.-G.K, Vogt C, Eik-Nes S.H. Abnormal gyration of the temporal lobe and megalencephaly are typical features of thanatophoric dysplasia and can be visualized prenatally by ultrasound. Ultrasound Obstet Gynecol 2012; 40: 230-234.
[4] Hevner RF. The cerebral cortex malformation in thanatophoric dysplasia: neuropathology and pathogenesis. Acta Neuropathol 2005; 110: 208-221.
Discussion Board
Winners
Dianna Heidinger United States Sonographer
Pawel Swietlicki Poland Physician
Umber Agarwal United Kingdom Maternal Fetal Medicine
Igor Yarchuk United States Sonographer
Dmitry Abelov Russian Federation Physician
Larysa Gazarova United States Physician
Andrii Averianov Ukraine Physician
Ana Ferrero Spain Physician
Alexandr Krasnov Ukraine Physician
Mayank Chowdhury India Physician
Adrian Popa Romania Physician
Nutan Thakur India Physician
Vera Osadshaya Russian Federation Physician
Vladimir Lemaire United States Physician
Ivan Ivanov Russian Federation Physician
Aysegul Ozel Turkey Physician
lan nguyen xuan Viet Nam Physician
Philippe Deblieck Germany Physician
Peter conner Sweden Physician
Marianovella Narcisi Italy Physician
Zhuldyz Zhumadilova Kazakhstan Physician
Nguyen Luân Viet Nam Physician
Victoria Giang Viet Nam Physician
Louise Konaris United States
ALBANA CEREKJA Italy Physician
Eda Özden Tokalıoğlu Turkey Physician
Deval Shah India Physician
Murat Cagan Turkey Physician
Charlotte Conturie United States Physician
gholamreza azizi Iran, Islamic Republic of Physician
Rasha Abo Almagd Egypt Physician
Ionut Valcea Romania Physician
Katrin Karl United States Physician
reyhan ayaz Turkey Physician
Hien Nguyen Van Viet Nam Physician
Borisova Elena Russian Federation Physician
Hoang My Trang United States Physician
Kareem Haloub Australia Physician
Anette Beverdam Netherlands Sonographer
Grzegorz Rak Poland Physician
Annette Reuss Germany Physician
Adumatta Michael Ghana Sonographer
Nguyen Xuan Cong Viet Nam Physician
shay kevorkian Israel Physician
SAVITA SHIRODKAR India Physician
Mary Jones United States Sonographer
Deniz Delibaş Turkey Physician
Flora Mirzoeva United States Sonographer
Jacqueline L J Cullen United States Sonographer
Rupal Sasani India Physician
Ruchika Mangla India Physician
Dolly Agrawal India Physician
Carmen de Luis Rodríguez Spain Physician
Le Tien Dung Viet Nam Physician
Tetiana Ishchenko Ukraine Physician
Costin Radu Lucian Romania Physician
Dr Fareeda Nikhat United Arab Emirates Physician
JHON YACILA Peru Physician
Steph Harmon United States Sonographer
Nora Fox United States Sonographer
Kelsey Daily United States Sonographer
Kylie Holihan United States Sonographer
Jill Smith United States Sonographer
Brittany Woods United States Sonographer
Eduardo Namura Di Thomaz Brazil Physician