2004-11-09-14 Congenital icthyosis © Vijayaraghavan www.thefetus.net/
S. Boopathy Vijayaraghavan, MD, DMRD, R.Lalitha, MBBS, DGO, A.K.Jaleel Ahmed, MBBS, DCH
This is a case report of congenital (Harlequin) ichthyosis. This condition can be shocking to parents. So it is better that the fetus is diagnosed early. The most definitive prenatal sonographic diagnosis of this condition is by 3D, which may not be done routinely without a suspicious 2D feature. In this case report, we suggest that the appearance of foot is the most easily seen and earliest 2D feature of this condition. We also reveal that the description of some of the 2D features described earlier is to be modified. This condition is very rare.
Introduction: Congenital ichthyosis, also called harlequin fetus, is a lethal autosomal recessive disorder resulting from a keratinising disorder. An externally thickened keratin layer of skin and diffuse plate like scales 1,2 characterizes it. Prenatal sonographic diagnosis has been described, with 2D findings of a persistently open mouth, echogenic amniotic fluid and fixed flexion deformity of the extremities 2-6. The 3D sonographic features have been described showing the morphological appearance typical of harlequin fetus, namely the open mouth with thick lips 2,6,7. Here, we describe the sonographic appearance of foot on a case of harlequin ichthyosis and review the literature.
A 25-year-old woman, gravida 3 and para 1, was referred for a routine sonography at 23 weeks of gestation. Her first child was a girl, delivered by caesarean section 4 years ago. She was normal. Her second pregnancy was a miscarriage at 8 weeks.
On sonography, the fetal biometry corresponded to 23 weeks. The amniotic fluid was subjectively normal. The feet of the fetus were abnormal. All the toes were hyperflexed and fixed in the same position (Fig 1). The foot to leg angle was normal. The survey of the rest of the fetus did not reveal any abnormality. At term, the patient had a caesarean section. The newborn showed classical features of congenital (Harlequin) ichthyosis. The feet showed fixed hyperflexion of the toes, corroborating the sonographic appearance (Fig 2). The video recording of the sonography was reviewed. The fetal facial features of congenital ichthyosis were not recognizable on it. The scan of profile of fetal face was not available. The movements of fetal limbs were seen. The fetal hands were clenched and opening of the fingers had not been recorded. It is doubtful whether this finding was looked for. The pediatrician had a video recording of the newborn, which was reviewed after the review of sonography video. The opening and closing movements of the mouth were seen in the newborn (video 1). There were movements of all the four limbs (video 2).
Toes hyperflexed and fixed:
Video 1 showing opening and closing movements of the mouth:
Video 2 showing movements of all the four limbs:
Congenital (harlequin) ichthyosis is a rare and devastating disorder. The appearance of the neonate can be shocking to parents and health care providers. Hence a prenatal diagnosis may help prepare them. Reverend Hart gave the first description of congenital ichthyosis in 1750. At birth the affected infant has a characteristic appearance of thick, whitish, armor-like skin, criss-crossed by deep red grooves often producing diamond-shaped forms resembling a harlequin costume 8,9. Facial anomalies include bilateral ectropion (complete eversion of the eyelids with occlusion of the eyes), eclabion (eversion of the lips), absence of external ears and nasal hypoplasia. The limbs are short and contained in a rigid sheath with hypoplastic fingers, toes and nails. Globally, the newborn appears to be encased in a tight, parchment-like membrane, which allows little movement and holds the limbs in a semi flexed position. The mouth remains permanently open and the infant is unable to suckle properly. Despite specialized treatment, death generally occurs within the first weeks of life due to skin infection. With close monitoring of the skin and eyes and treatment with vitamin A 10, survival has been prolonged, in one case until 22 months 11, in another until 3 years 12, and in another until 9 years 10, although the histology in this case was doubtful and perhaps indicative of a different type of ichthyosis.
In the human fetus, cornification of the skin begins between 14 and 16 weeks’ gestation. Under light microscopy, skin biopsies from harlequin fetuses show hyperkeratosis with hypertrophy of the horny layers measuring up to 10 times the normal thickness. Congenital ichthyosis is an autosomal hereditary disorder affecting both males and females. Recessive transmission is generally accepted13-15 although certain teams have suggested a dominant component16. Parents who have already had an affected child have a 25 % risk of recurrence in each pregnancy13.
The first case of antenatal diagnosis was reported in 1983 17. Fetoscopy was used to obtain a skin biopsy in a consanguineous pregnancy (first cousins) with a history of two previously affected infants. Diagnosis by skin biopsy can be established at 20-22 weeks’ gestation, although recently, diagnosis was achieved at 17 weeks’ gestation using electron microscopy of pillous follicles, whose cornification occurs a few weeks before that of the epidermis 18.
Prenatal 2D sonographic features of this condition have been described 2-7. The features included a persistently fixed open mouth, echogenic amniotic fluid, fixed flexion of the extremities, polyhydramnios, short digits, flat nose, bilateral club feet, aplasia of the ears, shriveled hands that did not open, flat face profile, thick lips and subnormal fetal movements. A definite diagnosis was not offered based on these features. Recently, 3D features of this condition have been described in 4 fetuses – three in unsuspected cases and one in second pregnancy of the mother who had an affected fetus earlier, the latter being one of the three unsuspected cases previously described. A definite diagnosis was offered in all these 4 fetuses leading to termination of fetuses at 30 7,32 6, 30 2 and 25 2 weeks. The 3D features described by these authors are very large open mouth with thick lips, flat nose and mottled skin. Of these 4 fetuses, 3 were described by same group of authors 2,7. The earliest sonographic diagnosis by 3D was at 22 weeks 2, made in the follow up of a second pregnancy after a first pregnancy with the same condition. In this case a scan was done at regular intervals of 15 days from early pregnancy. In unsuspected pregnancy the earliest diagnosis was by 3D at 30 weeks 2,7. The 3D was done after suspicious features were seen on 2D. Bongain, et al 2 have concluded that when there are suggestive features on 2D ultrasound, 3D ultrasound should be done to confirm the diagnosis.
Of the 2D features the most described feature was the flat face, which was also the earliest feature described in the fetus at 22 weeks, which was followed- up at regular intervals from early gestation. In unsuspected fetuses the same feature was picked up only at or after 30 weeks. Another feature described is fixed open mouth. A more specific description of this feature is, everted thick lips, resulting in a large open mouth, the lips failing to appose. However, the opening and closing movements of the lower jaw are present as seen in the newborn harlequin baby described here. Again, regarding the extremities, fixed deformities and subnormal movements are both described. Since limb movements are present in the newborn described here and the skin anomaly is less pronounced in the terminated fetus at 25 weeks, it could be concluded that good movements of the fetus are present in early pregnancy. So it is clear that the only useful 2D feature is a flat facial profile.
The 2D features of the feet described in earlier reports are short toes at 32 weeks and bilateral clubfeet at 30 weeks. In the fetus described here, the feet showed fixed extremely hyperflexed toes at 23 weeks, which was confirmed after birth. The same feature has probably been described as short toes in the earlier report of fetus at 32 weeks. We noted the same appearance in the published pictures of the fetuses, which were terminated at 25 weeks 2 and also at 32 weeks 6 respectively, but were not described by the authors of these articles. This feature of the toes has not been described in any other condition so far. Hence, the fixed extremely hyperflexed toes seems to be the earliest and easily recognizable 2D feature of this condition of congenital (harlequin) icthyosis..
In conclusion the 3D sonography is the most definitive method of prenatal diagnosis of congenital (harlequin) icthyosis. But there has to be a suggestive 2D feature, which will recommend a 3D examination. As per review of the available literature, the only useful 2D feature of this condition is a flat facial profile, which is difficult to recognize and is picked up only very late in gestation, unless it is suspected because of a previous sibling affected by the same condition The feature of fixed extremely hyperflexed toes, described in this article, is the earliest, definitive and easily detectable 2D feature of congenital icthyosis. This feature is more significant since it can be seen even in pregnancies with negative history.
1. Akiyama M. The pathogenesis of severe congenital ichthyosis of the neonate. J Dermatol Sci 1999; 21:96-104.
2. Bongain A, Benoit B, Ejnes L, Lambert JC and Gillet JY. Harlequin fetus: three-dimensional sonographic findings and new diagnostic approach. Ultrasound Obstet Gynecol 2002; 20:82-85.
3. Meizner I. Prenatal ultrasonic features in a rare case of congenital ichthyosis (harlequin fetus). J Clin Ultrasound 1992; 20:132–134.
4. Watson WJ, Mabee LM Jr. Prenatal diagnosis of severe congenital ichthyosis (harlequin fetus) by ultrasonography. J Ultrasound Med 1995; 14:241–243.
5. Montague E, Fox R, Mann R. Intra-amniotic debris identified at ultrasound scanning: a feature of congenital ichthyosis. Ultrasound Obstet Gynecol 1997; 9:350–351.
6. Nidhi V, Burton R, Smith–Levitin M. Three–dimensional Sonographic Findings in Congenital (Harlequin) Ichthyosis. J Ultrasound Med 22:737– 739, 2003.
7. Benoit B. Three–dimensional ultrasonography of congenital ichthyosis. Ultrasound Obstet Gynecol 1999; 13:380.
8. Plocoste V, Bonneau D, Deshayes M, De Giacomoni P, Kibler MP, Berthier M, Magnin G. Le syndrome du bébé arlequin. J Gynecol Obstet Biol Reprod 1992; 21:247–50.
9. Kouskoukis C, Minas A, Tousimis D. Ichthyosis congenital fetalis. Int J Dermatol 1982; 21:347–8.
10. Roberts LJ. Long term survival of a harlequin fetus. J Am Acad Dermatol 1989; 21:335-9.
11. Prasad RS, Pejaver RK, Hassan A, Al Dusari S, Wooldridge MA. Management and follow up of harlequin siblings. Br J Dermatol 1994; 130:650-3.
12. Lawyor F. Harlequin baby: inheritance and prognosis. Br J Dermatol 1987; 117:528.
13. Bottani A. On the inheritance of harlequin ichthyosis. Prenat Diagn 1994; 14:1099.
14. Williams ML, Elias PM. Genetically transmitted generalised disorders of cornification: the ichthyoses. Dermatol Clin 1987; 5:155-78.
15. Unamuno P, Pierola JM, Fernandez E, Roman C, Velasco JA. Harlequin fetus in four siblings. Br J Dermatol 1987; 116:569-72.
16. Suzumori K, Kanzaki T. Prenatal diagnosis of harlequin ichthyosis by fetal skin biopsy: report of two cases. Prenat Diagn 1991; 11:451-7.
17. Blanchet-Bardon C, Dumez Y, Labbé F, Lutzner MA, Puissant A, Henrion R, Bernheim A. Prenatal diagnosis of herlequin fetus. Lancet 1983; 8316:132.
18. Akiyama M, Suzumori K, Shimizu H. Prenatal diagnosis of harlequin ichthyosis by the examination of keratinized hair canal and amniotic fluid cells at 19 weeks’ estimated pregnancy. Prenat Diagn 1999; 19:167-71.
19. Vohra N, Rochelson B, Smith-Levitin M. Three-dimensional sonographic findings in congenital (harlequin) ichthyosis. J Ultrasound Med. 2003 Jul;22(7):737-9.
20. Berg C, Geipel A, Kohl M, Krokowski M, Baschat AA, Germer U, Gembruch U. Prenatal sonographic features of Harlequin ichthyosis. Arch Gynecol Obstet. 2003 Apr;268(1):48-51. Epub 2002 Jul 06. Review.