2010-06-23-11 Microcephalic osteodysplastic primordial dwarfism, type II © Julien www.TheFetus.net
Microcephalic osteodysplastic primordial dwarfism, type II
Emmanuel Julien, MD*, Eva Leinart MD, PhD**
* Centre hospitalier Le Mans, France.
** Inner Vision Women's Ultrasound, Nashville, Tennessee, USA;
Synonym: MOPD2; Majewski type
Incidence: very rare; 59 cases described (until 2009)
Findings
- Severe intrauterine growth retardation; birth weight less than 1500 grams
- Microcephaly, progressive (proportionate at birth)
- Short stature; shortening of distal and middle segments of the extremities
- Metaphyseal changes
- Epiphyseal delay
- Distinctive facial features: prominent nose; eyes; dysplastic ears, missing lobule
-
Joint dislocations
Prenatal complications
Pregnancies with affected fetuses are often accompanied by severe nausea or vomiting, pre-eclampsia, bleeding, premature delivery (mean delivery age 35 weeks). The placenta is small (ranging from half or quarter of normal placental size). Severe intrauterine growth retardation and fetal decelerations are often reason for an induction of early delivery.
Severe intrauterine growth restriction was present in all reported cases of microcephalic osteodysplastic primordial dwarfism type 2. The growth restriction usually starts around 12 weeks of gestation and progresses over the rest of the pregnancy. The birth weight ranges between 1100 - 1300 grams which corresponds with the weight appropriate for 28 weeks of gestation. Birth length at the time of delivery is between 30 - 40 centimeters.
Clinical findings
Head size is always small for age but it is proportionate to the rest of the body at the time of delivery. Microcephaly becomes apparent within the first year of life when the head growth is more decreased than the growth of the rest of the body. There maybe other anomalies present as well such as: ventriculomegaly, abnormal myelinization, abnormal gyry patterns, cyst or hypoplasia of the corpus callosum, craniosynostosis. Some affected individuals may have overgrown CNS vessels causing possible rupture and sudden death. Most of the individuals have some level of the developmental delay (IQ 50-90) but they have an excellent social skills and perform well in society.
Infants suffer from severe postnatal growth retardation. The maximum height in the adulthood is usually 100 cm with little or no response to growth hormone therapy. Most of the infants have feeding problems, nasogastric tube is often required. Individuals between age 3 - 5 often develop truncal obesity.
Many neonates have severe respiratory problems but grow out of them. This may include tracheal stenosis, laryngomalacia, decreased lung capacity.
Bones are thin with progressive widening of metaphysis of long bones. Fusion of epiphyses may appear as well. No obvious changes are usually seen on the postnatal X-ray images.
Inheritance
Autosomal recessive pattern. The responsible gene has not been identified yet. In 25 described cases of microcephalic osteodysplastic primordial dwarfism type 2, different mutations in PCNT2 gene (pericentrin-2 gene) were described. It seems that despite variants in clinical findings, condition is caused by loss of function of pericentrin-2.
Differential diagnosis
Differential diagnosis includes various syndromes with severe intrauterine growth restriction. These syndromes have usually higher birth weight, normal size head disproportionate to the abdomen circumference or microcephaly and mental retardation without skeletal dysplasia.
Antley-Bixler, Cornelia de Lange and Dubowitz syndrome have IUGR, microcephaly and characteristic facies but neonates are larger than the ones with microcephalic osteodysplastic primordial dwarfism type 2.
Seckel syndrome, MOPD 1, MOPD 3 have moderate IUGR and specific features which allows us to distinquish from microcephalic osteodysplastic primordial dwarfism type 2. Seckel syndrome has severe developmental delay with mental retardation and microcephaly but no skeletal dysplasia. microcephalic osteodysplastic primordial dwarfism type 1 has usually severe CNS malformations, wide proximal femur. microcephalic osteodysplastic primordial dwarfism type 3 has severe developmental delay and mental retardation with severe microcephaly, enlarged sella, hypoplastic pelvis and narrow face.
Case report
This a case of a 28-years-old G3 P2 patient. Her previous pregnancies were uncomplicated and she has 2 healthy children. Patient and her partner came from Africa, there was no evidence of consanguinity. Family and personal history were non-contributive.
First ultrasound scan showed increased nuchal translucency, NT = 7 mm, shortening of the spine and pronounced lumbo-sacral angle. We performed an amniocentesis and the karyotype of the fetus was normal 46 XX.
Second ultrasound scan was performed at 23 weeks of gestation. The abdominal circumference was in the 5th percentile, there was a very small chest and micromelic shortening of all the long bones, less then 5th percentile.
The profile of the fetus showed retrognathia. There was persisting thickening of the nuchal fold - 9 mm, hypertelorism with exophtalmia. Both ears were very small. The insertion of both AV valves was linear. Both feet were short. There was a camptodactyly of one hand. All extremities showed decreased mobility with right arm in a flexed position. The amount of the amniotic fluid was increased. Kidney and bladder were of normal appearance. There were no apparent cerebral anomalies. The clitoris was protruding. Parents wished to continue in their pregnancy.
The third ultrasound scan was performed at 30 weeks of gestation showed a severe intrauterine growth restriction and confirmed previous findings.
The patient delivered at 35 weeks of gestation, the neonate weighted 1030 grams and measured 31 cm. Baby died after delivery due to a severe pulmonary hypoplasia.
The autopsy report described the following findings:
- Severe intrauterine growth restriction
- "Frog-like" flexion of extremities
- Micro, retrognathia, absence of the posterior palate, small, low set ears with hypoplastic lobule, hypertelorism, low palpebral features
- Very short ribs
- Shortening of all long bones - corresponding with 29 weeks of gestation, right radius and humerus were joined together (synostosis)
- Scaphocephalic skull
- Camptodactyly of the 3rd finger, syndactyly of three toes
- Heart was normal
- Severe pulmonary hypoplasia, the lung size corresponded with 14 weeks of gestation
- Regression of both internal and external genitalia (rudimentary ovaries)
The final diagnosis according to the pathologist was Microcephalic osteodysplastic primordial dwarfism, type II (MOPD 2).
Images 1,2,3: 23 weeks, axial and sagittal view of the brain, note microcephaly and thickened nuchal fold, 9 mm.
Images 4,5: Image 4 shows exophtalmus. Image 5 shows hypertelorism.
Images 6,7: Transverse view of the thorax, note small thoracic circumference comparing normal sized heart to thorax.
Images 8,9: Image 8 shows a femur bone, it is thin, measuring less than 5th percentile. Image 9 shows a arthrogryphosis of the knee.
Images 10,11: Camptodactly of the 3rd finger.
Images 12,13: 33 weeks, Image 12 shows flexed fingers. Image 13 shows hypertelorism and exophtalmia.
Images 14,15: Image 14 shows hypertelorism. Image 15 shows retrognathia.
Images 16,17: Image 16 shows a deffect of the palate demonstrated by Doppler imaging while swallowing. Image 17 shows a pericallosal artery.
Images 18,19: Image 18 shows dolichocephaly. Image 19 shows linear insertion of both AV valves.
Images 20,21: 33 weeks, image 20 shows femur measuring less than 5th percentile, 5 weeks lagging. Image 21 shows feet which are markedly shortened.
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Images 22,23: Sagittal view of the spine, note shortened spine and angulation between lumbar and sacral spine.
Images 24,25: Image 24 shows a small chest and protuberant abdomen. Image 25 shows increased amount of the amniotic fluid which is echogenic.
Image 26: Neonate after delivery, note facial features, low set small ears, retrognathia. Small chest, flexion of all extremities, camptodactyly of the middle finger.
References:
1. Hall JG, Flora C, Scott CI, Pauli RM, Tanaka KI. Majewski Osteodysplastic Primordial Dwarfism Type II (MOPD II): Natural History and Clinical Findings. Am J Med Genet. 2004;130A:55-72.
2. OMIM; MIM #210720, MICROCEPHALIC OSTEODYSPLASTIC PRIMORDIAL DWARFISM, TYPE II.