LETHAL MULTIPLE PTERYGIUM SYNDROME (LMPS)

Lethal multiple pterygium syndrome and its variants are a heterogeneous group of disorders affecting lymphatics and muscle development (1). The Pathophysiology has not yet been established, but one theory postulates that the manifestations are due to a genetically determined insult that causes both a fetal akinesia sequence and jugular lymphatic obstruction sequence. The fetal akinesia hypothesis suggests that early embryonic immobility is the critical factor in the pathogenesis of the pterygia. Fetal skin appears to grow passively in response to movement of underlying structures. The lack of fetal movement in akinesia results in webs across large joints. The earlier and more severe the limitation of movement, the larger the web (1).

This classical syndrome consists of congenital contractures, pterygia (skin webs across joints). Other associated features include ocular hypertelorism, nuchal edema or cystic neck masses, loose skin, decreased muscle mass and hypoplastic lungs.

• Three variants are described (2):
• Bartsocas-Papas syndrome (lethal popliteal syndrome).
  Without bony fusions but limbs are tightly flexed.
• Lethal multiple pterygium syndrome with fusion of vertebral bodies.
• Lethal multiple pterygium syndrome with congenital bony fusions.

Thus classification has been challenged because occasionally different subtypes are found in the same families (1).

• Inheritance
• Usually autosomal recessive.
• An X-linked recessive inheritance has been described (3).
• Karyotype is normal but essential to perform as the presence of cystic hygromas have a high association with chromosomal aneuploidy.

ULTRASOUND

Antenatal diagnosis without a history of a prior affected sibling is rare (4,5). Antenatal detection of the pterygia has been described, but visualization of the webs is unusual (4).

• Limbs.
• Contractures and flexion deformities across joints.
• Formation of pterygia (chin to sternum,cervical, axillary, antecubital, crural, popliteal). Pterygia represent webbing of the skin across a joint is an essential feature of this syndrome. The pterygia are thick and extensive and produce the severe flexion contractures of multiple joints resulting in akinesia and preclude fetal movement.

• Long bones are undermodelled with normal length except for ulnar overgrowth.

• Cystic hygromata and fetal hydrops are almost always present (8).
• Facial anomalies (hypertelorism, flattened nose, micrognathia, low set ears and epicanthic folds).
• Head (brachycephaly with soft bones).
• Spine (scoliosis may occur).
• Pelvis (hypoplasia of iliac, ischial and pubic bones).
• Polyhydramnios.
• Hydrops fetalis.
• Hypoplasia of heart, lungs, gastrointestinal and genitourinary systems.
• Cardiac defects, diaphragmatic hernia, omphalocele.
• Eye malformations (congenital cataracts and corneal ulceration).
• Postural and limb deformities are present in the variant forms.
• Intrauterine growth restriction (IUGR).
• Short umbilical cord.

Lethal Multiple Pterygium Syndrome Persistent flexure contraction at the knee. Scoliosis of spine. Large nuchal cystic hygroma.

DIFFERENTIAL DIAGNOSIS

• Pena Shokeir phenotype.
• Arthrogryposis multiplex congenital.
• Congenital myotonic dystrophy.
• Non-lethal pterygium syndrome (joint contractures are confined to the knees).
• Fowler syndrome.

Contractures in combination with cystic hygroma usually distinguish LMPS from the above conditions. Pterygia have been described rarely in Pena-Shokeir syndrome type I and non-lethal pterygium syndrome. The pterygia are however usually smaller and less extensive.

PROGNOSIS

The majority of fetuses with this disorder die in the second trimester. The few that do survive pregnancy die in the early neonatal period from pulmonary hypoplasia.

REFERENCES

1. Moerman P, Fryns JP, Cornelis A et.al. Pathogenesis of lethal multiple pterygium syndrome. Am J Med Genet 1990;35:415-421.
2. Hall JG. Editorial comment: the lethal multiple pterygium syndromes. Am J Med Genet 1984;17:803-807.
3. Lockwood C, Irons M, Troiani J et.al. The prenatal sonographic diagnosis of lethal multiple pterygium syndrome: A heritable cause of recurrent abortion. Am J Obstet Gynecol 1988;159:474.
4. Entezami R, Runkel S, Kunze J et.al. Prenatal diagnosis of lethal multiple pterygium syndrome type II. Fetal Diagn Ther 1998;13:35.
5. Sciarrone A, Verdiaglione P, Botta G et.al. Prenatal diagnosis of lethal multiple pterygium syndrome in mid pregnancy. Ultrasound Obstet Gynecol 1998;12:218.
6. Zeitune M, Fejgin MD, Abramowicz J et.al. Prenatal diagnosis of the pterygium syndrome. Prenat Diagn 1988;8:145-149.
7. Die-Smulders CEM, Vonsee HJ, Zandvoort JA et.al. The lethal multiple pterygium syndrome: prenatal ultrasonographic and post mortem findings; a case report. Eur J Obstet Gynecol Reprod Biol 1990;35:283-289.
8. Anthony J, Mascarenhas L, O'Brien J et.al. Lethal multiple pterygium syndrome. The importance of fetal posture in mid-trimester diagnosis by ultrasound: discussion and case report. Ultrasound Obstet Gynecol 1993;3:212-216.
9. Meizner I, Hershkovitz R, Carmi R et.al. Prenatal ultrasound diagnosis of a rare occurrence of lethal multiple pterygium syndrome in two siblings. Ultrasound Obstet Gynecol 1993;3:432-436.
10. Hertzberg BS, Kliewer MA, Paulyson-Nunez K. Lethal multiple pterygium syndrome: Antenatal ultrasonographic diagnosis. J Ultrasound Med 2000;657:657-660.