Patricia C. Freeman, RDMS, RT*, Philippe Jeanty, MD, PhD

Synonyms: None.

Prevalence: 0.1-10:10,000⁴, M1:F9¹⁶.

Definition: Neural tube defect involving the occiput and inion combined with rachischisis of the cervical and thoracic spine with retroflexion of the head.

Etymology: inion (Gr. inion back of the head), encephalos (Gr. enkefalos brain).

Etiology: Unknown, but seasonal and yearly variations exist. Other factors include low parity and low socioeconomic status²².

Pathogenesis: Unknown.

Associated anomalies: Anencephaly, cephalocele, holoprosencephaly, agnathia-microstomia-synotia, palatal anteversion, spina bifida, omphalocele, gastroschisis, diaphragmatic hernia or agenesis, pulmonary hypoplasia or hyperplasia, cardiac malformations, renal anomalies, overgrowth of the arms compared to the legs, genu recurvatum, arthrogryposis, club-foot, gastrointestinal atresia^{1,5,7-15, 23-32}.

Differential diagnosis: Klippel-Feil, anencephaly with spinal retro­flexion.

Prognosis: Fatal.

Recurrence risk: As for other neural tube defects: 1-4%.

Management: As for disease with fatal outcome.

MESH Monsters-diagnosis; Brain-abnormalities; Head-abnormalities; Neck-abnormalities Neural-Tube-Defects; Skull-abnormalities; Occipital-Bone-abnormalities; Foramen-Magnum-abnormalities; Spina-Bifida-diagnosis; Spine -abnormalities; Cervical-Vertebrae-abnormalities; Thoracic-Vertebrae-abnormalities ICD9 740.2 CDC 740.210

* Address correspondence to Patricia C. Freeman, RDMS, RT Department of Radiology and Radiological Sciences, Vanderbilt University Medical Center, 21^st and Garland Ave, Nashville, TN 37232-2675. Ph 615-322-0999 Fax 615-322-3764

Introduction

Iniencephaly is an uncommon and fatal neural tube defect involving the occiput and inion combined with rachischisis of the cervical and thoracic spine with retroflexion of the head¹. The entity was first described by Saint-Hilaire². Two main groups were classified by Lewis: iniencephaly apertus which has an encephalocele and iniencephaly clausus which has a spinal defect but no cephalocele¹. There is much discrepancy in the incidence of iniencephaly. Reports vary from 0.1-10:10,000⁴. The incidence is probably much higher than previously reported, which is due to the failure to recognize the entity. Seasonal and yearly variations exist. Other risk factors include low parity and low socioeconomic status²². Girls are involved 90% of the time. The differential diagnosis includes Klippel-Feil syndrome and anencephaly with retroflexion of the head.

Case reports

Case 1

A 22-year-old primigravida was referred for a routine ultrasound examination due to an elevated alpha-fetoprotein. The ultrasound revealed multiple anomalies including acrania, a short distorted spine, omphalocele, clubfeet and club hands. It was felt that these defects represented the iniencephaly sequence. Due to the extremely poor prognosis, termination was offered to the parents. Prostin termination resulted in a spontaneous vaginal delivery of a 164g fetus. The autopsy confirmed acrania with a cervical and thoracic myelomeningocele. The rachischisis extended from the cervical through lumbar spine. The base of the skull was also malformed. Also present was a 2.0 x 2.0 x 1.5 cm omphalocele containing herniated small bowel. Trisomy 18 was suspected, although despite repeated attempts at tissue culture with a variety of culture media, no cell growth was observed.

Fig. 1: Case 1. Top: A very short spine with severe disorganization of the cervical vertebrae is associated with acrania. Right: Radiographs and photographs of the fetus. Note the retroflexion, the absence of neck and the acrania (the brain has been separated during manipulations of the fetus).

Case 2

A 20-year-old primigravida was transported to our medical center from out of state in pre-term labor at 32 weeks gestation. An ultrasound earlier in her pregnancy at an outside hospital revealed multiple anomalies. Our examination demonstrated multiple fetal anomalies consistent with iniencephaly, microcephaly, holoprosencephaly, rachischisis, severe hypotelorism, midline cleft lip, bilateral club feet, and a probable proboscis. Spontaneous vaginal delivery resulted in a 1559g non-viable female fetus with Apgars of 1 and 0. Multiple defects were present: rachischisis, club and rocker bottom feet, and microcephaly with low set ears. The karyotype revealed 46XX. 

Fig. 2: Case 2. Far left: Cervical meningomyelocele. Left: Soft-tissue view that demonstrates the left cheek, eye and ear. Notice the retroflexion of the head and the absence of neck.

Case 3

A 27 year-old primigravida was referred from out of state at 23 weeks gestation. A sonogram obtained at a private physician"s office demonstrated a large skull and spine abnormality. An alpha-fetoprotein had not been obtained. An amniocentesis for chromosome analysis and ultrasound were performed at the time of admission. The ultrasound revealed a large occipital cephalocele arising from the left part of the lambdoidal suture. This was felt to represent an encephalomeningocystocele. The cervical and high thoracic spine were markedly abnormal with fusion and absent vertebrae in the high thoracic and cervical region with the ribs originating in abnormal positions. The rib cage and chest were deformed due to the abnormal ribs.

Fig. 3: Case 3.: Disorganization of a shortened spine with (left) a large encephalocystomeningocele.

The autopsy findings included a large closed meningoencephalomyelocele and secondary deformities of the head, face, and shoulder girdle. The defect extended from the occipital region of the cranium to approximately the 8^th thoracic vertebral level. The head was grossly malformed and no discrete neck was apparent. The ears were somewhat lowset and posteriorly rotated. The external genitalia were that of a male infant and the testes were identified in the inguinal canals. The posterior facets of the cervical and upper thoracic vertebrae were absent. No caudal neural tube defect was identified.

Discussion

Diagnostic criteria

The diagnostic criteria for iniencephaly are^9,10:

·        A variable deficit of the occipital bones resulting in an enlarged foramen magnum

·        Partial or total absence of cervical and thoracic vertebrae with an irregular fusion of those present, accompanied by incomplete closure of the vertebral arches and/or bodies

·        Significant shortening of the spinal column due to marked lordosis and hyperextension of the malformed cervical-thoracic spine

·        Upward turned face and mandibular skin directly continuous with that of the chest due to the lack of neck.

Most cases diagnosed prenatally have presented with high alpha-fetoprotein and/or polyhydramnios. The diagnosis is made on the extreme dorsal flexion of the head, the abnormally short and deformed cervical and thoracic spine and the overall shortening of the fetus^23-32. In all three of our cases, a section could demonstrate the entire spine in a single view and it was shorter than a normal limb. The retroflexion of the head and the spinal disorganization is visible on medial-sagittal scans of the spinal column¹⁶.

Embryology

Iniencephaly is a neural tube defect. The time of onset is probably only a few days later than anencephaly.

Pathogenesis

This defect is different from anencephaly in that the anterior neuropore has closed in iniencephaly. The cervical vertebrae are also normal in anencephaly, while they are very abnormal in iniencephaly. On microscopic examination of the brain, several anomalies have been detected "including microencephaly, polymicrogyria, heterotopic glial tissue in the leptomeninges, atresia of the ventricular system, marked disorganization of the brain stem, vermian agenesis, large cerebellar cyst, and disorganization of the spinal cord tissue"³².

Associated anomalies

Several other anomalies have been associated with iniencephaly. These include anencephaly, cephalocele, holoprosencephaly, agnathia-microstomia-synmelia, spina bifida, omphalocele, gastroschisis, diaphragmatic hernia or agenesis, pulmonary hypoplasia or hyperplasia, cardiac malformations, renal anomalies, overgrowth of the arms compared to the legs, genu recurvatum, arthrogryposis, club-foot and gastrointestinal atresia^1,5,7-15.

Differential diagnosis

The differential diagnosis includes Klippel-Feil syndrome (shortness of the neck associated with fusion of cervical vertebrae), anencephaly, and a cervical myelomeningocele⁴. The differentiation between iniencephaly clausus and Klippel-Feil syndrome is difficult and controversial. Some authors feel that Klippel-Feil syndrome may be the mildest form of iniencephaly¹⁷. The distinction between iniencephaly apertus and anencephaly with spinal retroflexion relates to the time of onset⁵. Anencephaly arises prior to the closure of the cephalic neural folds at 24 days gestation¹⁸. Iniencephaly, on the other hand, arises after the cephalic neural tube has closed⁵.

Prognosis

Iniencephaly apertus is always fatal in the neonatal period¹⁴. Four cases of long-term survival of very mild iniencephalus clausus have been reported^19,20, although in these cases, the deformity was minimal and they should probably have been classified as Klippel-Feil syndrome.

Summary

Iniencephaly has previously been regarded as a rare neural tube defect. With a better understanding of the ultrasound criteria for the iniencephaly sequence, more cases will be diagnosed with sonography.

References

1. Lewis HL: Iniencephalus. Am J Obstet 35;11-53, 1897.

2. Saint-Hilaire IG: Iniencephalus. In Histoire des Anomalies de l"Organisation. Paris J.B. Bailliere. (ed). Vol.2, Paris, 1836 pp 308-310.

3. Bowden RA, Stephens TD, Lemire RJ: The association of spinal retroflexion with limb anomalies. Teratology 21; 53-59, 1980.

4. Romero R, Pilu G, Jeanty P et al: Prenatal diagnosis of congenital anomalies. Norwalk, CT: Appleton and Lange, 1988 pp. 64-67.

5. Lemire, RJ, Beckwith, B, Shepard TH: Iniencephaly and anencephaly with spinal retroflexion, a comparative study of eight human specimens. Teratology 6:27-36, 1972.

6. Gunderson CH, Greenspan RH, Glaser G, et al: The Klippel-Feil syndrome: genetic and clinical reevaluation of cervical fusion. Medicine 46: 491-512, 1967.

7. Osborne DF: Iniencephalus. Can Med Assoc J 59:474-475, 1948.

8. Stark AM: A report of two cases of iniencephalus. Br J Obstet Gynaecol 58:462-464, 1951.

9. Cimmino CV, Painter JW: Iniencephaly. Radiology 79:942-944, 1962.

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18. Streeter GL: Developmental horizons in human embryos. Age groups XI to XXIII. Embryology reprint Vol. II, Carnegie Inst. Wash., Washington DC 1951.

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25. Guilleux MH, Serville F, Gaillac D, et al: Diagnostic echographique antenatal de l"iniencephalie. A propos d"un cas. J Gynecol Obstet Biol Reprod (Paris) 16:85-9, 1987.

26. Foderaro AE, Abu-Yousef MM, Benda JA, et al.: Antenatal ultrasound diagnosis of iniencephaly. JCU 15:550-4, 1987.

27. Meizner I, Bar-Ziv J: Prenatal ultrasonic diagnosis of a rare case of iniencephaly apertus. JCU 15:200-3, 1987.

28. Kapoor R, Saha MM: Prenatal diagnosis of iniencephaly—(report of 2 cases). Australas Radiol 31:400-3, 1987.

29. Khristov A, Ivanov L, Stoianov M: Echographic diagnosis of iniencephaly. Akush Ginekol Sofiia 25:84-6, 1986.

30. Morocz I, Szeifert GT, Molnar P, et al: Prenatal diagnosis and pathoanatomy of iniencephaly. Clin Genet 30:81-6, 1986.

31. Wilson WG, Randall ME, Babler WJ: Palatal anteversion as part of the iniencephaly malformation sequence. J Craniofac Genet Dev Biol 5:5-10, 1985.

32. Morocz I, Molnar P, Toth Z, et al: Diagnostic criteria of iniencephaly based on the authors" own cases and the review of the literature. Morphol Igazsagugyi Orv Sz 25:58-65, 1985.

33. Aleksic S, Budzilovich G, Greco MA, et al: Iniencephaly: a neuropathologic study. Clin Neuropathol 2:55-61, 1983.