Proboscis

A proboscis is a developmental disorder of the nasal placodes, characterised by a blind-ended, tube-like appendage that is commonly located in the midface between or above the eyes. A midline proboscis is always associated with arhinia, hypotelorism/ cyclopia and holoprosencephaly. Extremely rare forms are located next to the vertical midline of the face and are often associated with a normal or hemi nose, eye anomalies and clefts but can be isolated. 

ICD-10: Q30.8, Q30.9.

A midline proboscis is associated with holoprosencephaly which has birth prevalence in the range of 1:10.000.¹ A spectrum of facial anomalies such as proboscis is encountered in 80% of holoprosencephaly cases.² Atypical forms of proboscis located next to the midline are very rare and have an incidence of less than 1:100.000.³ The incidence of these lateral proboscises appears to be higher in males than in females with a 3:1 male/female ratio.4

The developmental precursors of the nose are the neural crest cells, which start to migrate toward the midface at around six weeks’ gestation. The formation of the nose starts with the nasal placodes (oval thickenings), which appear symmetrically on the frontal prominence by the end of six weeks’ gestation. The nasal pits (future nostrils) divide the placodes into medial and lateral nasal prominences. In the vast majority of proboscis cases the two nasal placodes fuse into an elongated tube-like appendage in the midline of the face of the fetus. These midline proboscises are typically associated with holoprosencephaly.  A hypothesis is described by Cohen in which holoprosencephaly with severe facial dysmorphia like proboscis is thought to arise from faulty embryonic interaction between the cephalic tip of the notochordal plate, the neuroectoderm of the brain plate and the oral plate.⁵ Several genetic causes and heterogeneous risk factors like maternal diabetes, alcohol and retinoic acid consumption are known to be linked to holoprosencephaly.¹

In rare cases, one nasal placode develops into a tube-like appendage next to a ‘normal’ semi nose or a super numerous nasal placode develops into a tube-like appendage next to a normal nose. The embryologic mechanism responsible for the development of an atypical proboscis has not been defined.  Imperfect fusion of the nasal and maxillary processes is probably a causal factor. A primary insult in the nasal placode has been suggested as the likely mechanism for development.⁶ Most atypical proboscis cases are spontaneous, although this condition has been described in consanguineous parents, which might suggest an autosomal recessive mode of inheritance.⁴

A proboscis usually has a single blind ending nostril. In most cases of midline proboscises, the olfactory bulb is rudimentary and the lacrimal duct, nasal bone, nasal cavity, vomer, maxillary sinus, cribriform plate, and ethmoid cells are missing. A midline proboscis has rarely been reported in the absence of severe eye anomalies and alobar holoprosencephaly. A midline proboscis may be associated with the very rare congenital anomaly otocephaly.⁸ Depending on its location, the holoprosencephalic midline proboscis has been classified into various types and forms a spectrum of craniofacial changes associated with holoprosencephaly. Three types can be distinguished: 
1. In cyclopia, a single median orbit (with a single or partly divided eye) is associated with arhinia and proboscis formation above the eye. 
2. In ethmocephaly, two separate hypoteloric eyes are associated with arhinia and proboscis formation above or between the eyes.
3. In cebocephaly, a single-nostril proboscis-like nose is present at a normal position, usually with hypotelorism.

In exceptional cases a lateral proboscis develops next to the vertical midline of the face and represents abnormal formation of one side of the nose. The contralateral side of the nose is normal developed. Rarely,, the lateral proboscis is additional to a normally formed nose. Ocular hypertelorism may be present. Exceptionally rarely, a lateral proboscis is present bilaterally.^{9, 10} The lateral proboscis can be found from the upper eyelid down to the alar base but most typically at the inner canthus of the eye. The lateral proboscis may be isolated but eye anomalies or clefts can be present. A classification of lateral proboscis is suggested by Khoo:¹¹
1. Lateral proboscis with normal nose (least common). Synonyms are supernumerary or accessory proboscis. Both nostrils are formed and the proboscis occurs additionally. The accessory proboscis arises from a supernumerary nasal placode.
2. Lateral proboscis with an ipsilateral deformity of the nose 
3. Lateral proboscis with ipsilateral deformity of the nose, eye and/or ocular adnexa (the most common type);
4. Lateral proboscis with ipsilateral deformity of the nose, eye and/or ocular adnexa, plus cleft lip and/or palate.

Occasionally a disruptive proboscis is described occurring from an embryonic hamartoma arising in the primitive prosencephalon.¹²
 

Midline proboscises are always associated with severe holoprosencephaly (alobar holoprosencephaly or rarely severe semilobar holoprosencephaly). The risk of chromosomal anomalies (especially trisomy 13) and syndromes is high.¹
Lateral proboscises may be isolated anomalies, but there is a risk of ocular anomalies or clefts. Cases with an encephalocele have been published.¹³
 

The recurrence risk for a holoprosencephalic proboscis is variable and depends on the presence of an underlying chromosomal anomaly or syndrome. Genetic consultation is recommended.¹

The recurrence risk for a lateral proboscis is very low, but may be higher for consanguine couples.⁴

The midsagittal profile view of the face permits recognition of the midline proboscis and the concomitant arhinia. The axial views permit detection of the proboscis, hypotelorism, cyclopia and arhinia. 3D imaging can be very helpful. The diagnosis of midline proboscis is straightforward in most cases. Severe face and brain anomalies don’t easily escape attention and diagnosis can be made in the first trimester.^{14, 15}

Lateral proboscis is rare but prenatal diagnosis has been described. Axials views, tomographic ultrasound imaging or 3D rendered images are most helpful to identify the characteristic appearance of a proboscis next to a central (hemi)nose.^{16, 17}

The diagnosis of a midline proboscis with holoprosencephaly is usually straightforward.¹

In case of a lateral proboscis, facial tumors like a glioma or an encephalocele should be included in the differential diagnosis.

The diagnosis of proboscis can be made from 10 weeks’ gestation, especially when a targeted vaginal ultrasound examination is performed. Three-dimensional rendered ultrasound may be very helpful in recognising the type of proboscis. When a proboscis is suspected the patient should be send to an expert centre for an advanced ultrasound examination to determine the anomaly and search for associated structural pathology. Invasive diagnostic testing is recommended in addition to  genetic counselling. 

A midline proboscis with alobar holoprosencephaly carries a very bad prognosis. Children with alobar holoprosencephaly rarely survive the immediate postnatal period.¹⁸ The risk of chromosomal anomalies (especially trisomy 13) and syndromes is high.¹

Cases with lateral proboscises generally carry a good prognosis. Intelligence is usual normal. Aesthetic and psychological problems are often a concern. 

If a proboscis is recognised on ultrasound examination an advanced scan should be performed and fetal array is recommended (due to the high association with trisomy 13). Genetic consultation is important with dysmorphology examination and interview of the family to determine risk factors and identify mild manifestation. In countries where termination of pregnancy is possible, this should be discussed with the couple, especially in cases with midline proboscis and holoprosencephaly. In cases with lateral proboscis, the aesthetic and psychological problems need attention and require multidisciplinary (psychologist, social worker, otolaryngologist, ophthalmologist, neurosurgeon, plastic surgeon) management. MRI may help to differentiate a lateral proboscis from an encephalocele.

1. https://www.isuog.org/education/visuog.html. Obstetrics/Brain/ Abnormal CSP/Holoprosencephaly.
2. Solomon BD, Gropman A, Muenke M. Holoprosencephaly Overview. In: GenerReviews. Adam MP, Ardinger HH, Pagon RA, Wallace SE, Bean LJH, Stephens K, Amemiya A, editors. Seattle (WA): University of Washington, Seattle; 1993-2018. 
3. Chauhan DS, Guruprasad Y. Proboscis Lateralis. J Maxillofac Oral Surg 2010;9(2):162-165.
4. Guerrero J, Cogen M, Kelly D, Wiatrak B. Clinicopathologic Reports, case reports, and small case series. Proboscis lateralis. Archives Ophthalmology 2001;119:1071-1080.
5. Cohen MM, Jr., Jirasek JE, Guzman RT, Gorlin RJ, Peterson MQ. Holoprosencephaly and facial dysmorphia: nosology, etiology and pathogenesis. Birth Defects Orig Artic Ser 1971;7(7):125-135.
6. Rontal M, Duritz G. Probocis lateralis: case report and embryologic analysis. Laryngoscope 1977;87(6):996-1006.
7. Wang SJ, Wang YW, Roy FH. Proboscis lateralis, microphthalmos, and cystic degeneration of the optic nerve. Ann Ophthalmol 1983;15(8):756-758.
8. Lin H-H, Liang R-I, Chang F-M, Chang C-H, Yu C-H, Yang H-B. Prenatal diagnosis of otocephaly using two‐dimensional and three‐dimensional ultrasonography. Ultrasound Obstet Gynecol 1998;11:361-363.
9. Harada T, Muraoka M. Proboscis lateralis: a rare bilateral case. Ann Plast Surg 2001;47(3):350-351. 
10. Rosen Z, Gitlin G. Bilateral nasal proboscis. Arch Otol 1959;70:545-550.
11. Khoo BC. The proboscis lateralis—a 14-year follow-up. Plast Reconstr Surg1985;75(4):569-577.
12. Mladina R, Manojlović S, Markov-Glavas D, Subarić M. An unusual case of heminasal aplasia: proboscis lateralis or cystic teratoma? J Craniofac Surg 2003;14(1):41-45.
13. Boahene DKO, Bartley GB, Clay RP, Thompson DM. Heminasal proboscis with associated microphthalmos and encephalocele. Otolaryngology 2005;16(2):300-306.
14. Wong HS, Lam YH, Tang MHY, Cheung LWK, Ng LKL, Yan KW. First‐trimester ultrasound diagnosis of holoprosencephaly: three case reports. Ultrasound Obstet Gynecol 1999;13(5):356-359.
15. Blaas H-GK, Eik‐Nes SH, Vainio T,  Vogt Isaksen C. Alobar holoprosencephaly at 9 weeks gestational age visualized by two‐ and three‐dimensional ultrasound. Ultrasound Obstet Gynecol 2000;15:62–65. 
16. Mehta L, Petrikovsky B, Tydings L, Lundberg J. Lateral nasal proboscis: antenatal diagnosis and counseling. Obstet Gynecol 1999;94:815-817.
17. Makogon AV, Morozova LS, Karpov MA, Andryushina IV. Proboscis lateralis. www.TheFetus.net; 2011-01-31.
18. Cohen MM, Jr. Holoprosencephaly: clinical, anatomic, and molecular dimensions. Birth Defects Res A Clin Mol Teratol 2006;76(9):658-673.

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