CLINICAL CASE

1997 : Miscarriage (9 weeks)

1998 :

Fetal hydrops with severe dysmorphism forced termination of pregnancy in 18th week (D&C procedure). Ultrasound showed light hydramnios and intrauterine growth retardation (IUGR) of male fetus (about 15 weeks). At first, abnormalities of some fingers and toes was attributed to amniotic band syndrome but no constriction ring was found. Then skin could become detached because of fetus maceration.

Clinical synopsis :

• Thick placenta with many blood clots
• Umbilical cord too long by 7 cm (no placental pathology was investigated)
• Hydrops & ascites with nuchal translucency thickness
• Microcephaly or rather the weight of brain and the cranium were normal for 14-15 weeks. Extensive autolysis of the brain should be noted.
• Triangular long face : bird-headed appearance
• Receding forehead
• Hypoplastic eyes with hypertelorism and microphthalmia (according to the pathologist)
• Narrow-shaped and downslanting or antimongoloid slant of palpebral fissures (as shown on pictures)
• Microtia with malformed and low-set ears (not rimmed), hypoplasia of lobes
• Protrusion of the nose (very prominent and pointed)
• Important micrognathia and retrognathia
• Short neck with oedema
• Tapering fingers and toes with hypoplastic nails (according to the pathologist)
• Abnormal space between the two big toes and the second toes (as shown on pictures)
• Absence of epiphyseal ossification at the phalanges : clinodactyly, camptodactyly ?
• Legs bone asymmetry : absence or hypoplasia of fibula on the right-hand side
• Micropenis (hypoplastic testes in pelvis were not examined under a microscope) but the "micropenis" may be normal for a fetus whose weight was 67 grammes...
• Pulmonary hypoplasia (may be due to hydrops) but normal lung lobation
• Preductal aortic stenosis without other heart abnormality (according to the pathologist)
• Asplenia but the spleen (same colour as liver) could have been missed on a fetus whose weight was 67 grammes...
• Hypoplasia of adrenal gland
• Hepatomegaly, liver (strongly macerated) symmetric on the halfway line according to the pathologist. But then where was the gall-bladder ?

According to the pathologist, abnormal situs could suggest a right but incomplete isomerism. This kind of heterotaxy (defects of lateralization) is also called Ivemark Syndrome.

Microscopically (despite marked autolysis) :

• Bilateral cytomegaly of adrenal gland
• Placenta : very involutive and fibrous with subtrophoblastic linear calcification
• Nucleomegaly at the myocardium
• Thickening of the endocardium with myocardial fibrosis

1999 :

Termination of pregnancy was performed as well in the case of female fetus at 17 weeks of gestation because of hydrops with intrauterine growth retardation (IUGR about 13 weeks). But the pathologist could not compare this one to the first one because of D&C procedure. The only features are tapering fingers and toes (typical of hydrops), normal umbilical cord (10 cm), aplasia of umbilical artery. However, one ultrasound negative reveals abnormal profile with receding forehead and retrognathia ; which could be the same dysmorphic syndrome as in 1998.

Microscopically :

• Calcified aspect of subtrophoblastic basal membrane
• Many small and fibrous villosities
• In heart, large mass of myocardial fibers ("balloon-shaped" and clear) with nucleomegalies

The question still remains unsolved

A determining cause was not discovered, despite chromosomal tests (normal karyotypes of parents and babies) and viral analyses (toxoplasmosis, rubella, herpes, CMV, parvovirus B19 for IgM, direct Coomb negative).

In both cases, myocardial fibrosis and nucleomegaly could suggest a myocardiopathy : rhabdomyomatosis (rhabdomyoma) or lipidic storage as described in histiocytoid cardiomyopathy (some forms are linked to mitochondrial pathologies).

In case of recurrence, every metabolic disease involving mitochondria or cholesterol (Smith-Lemli-Opitz syndrome) should be ruled out.

IUGR, i.e. microcephalic dwarfism, dysmorphic facies and hypoplasia of the fibula for the first fetus may raise the possibility of Seckel Syndrome. But the X-Ray is not good enough to show hands and feet bones in detail. Consequently, this diagnosis is not reliable.

Although no common aetiology between these pathologies was found in the literature, there may be a vital lead...

Any information or previous experience would be very helpful and more than appreciated.