Post axial acrofacial dysostosis

Philippe Jeanty, MD, PhD

Nashville, TN

Synonyms:  Miller syndrome or Genee-Wiedemann syndrome.

Definition:¬† ‚ÄúAcrofacial dysostoses‚ÄĚ are disorders involving craniofacial defects and limb anomalies. The most common form is preaxial and it is called Nager acrofacial dysostosis. The postaxial form of acrofacial dysostosis (POADS = postaxial acrofacial dysostosis syndrome) is the Genee-Wiedemann or Miller syndrome.


Pre- and postaxial refer to the axis of the embryo limb. Thus, preaxial would be the side of the thumb and big toe.

Preaxial acrofacial dysostoses occur about twice as commonly as postaxial.

The former appears to be about twice as common as the latter with well-documented autosomal dominant and recessive occurrences in both conditions.

History:  First reported by Genée[i] and Wiedeman[ii] and then by Miller in 1979[iii] in 3 patients.

Case report:

By Rama Murthy, MD, Bangalore, India

A 21-year-old second gravida presents for a growth assessment scan at 32 weeks. Her anomaly scan done at 20 weeks was said to be normal. Several anomalies were recognized during the scan. On describing these anomalies, the patient concedes that her three-year-old son has similar findings.

The umbilical cord contains 2 vessels


The toes of the left foot demonstrate absence of one toe (most likely the 5th toe)


The mouth presents a bilateral cleft lip, micrognathia and the 3D of the ear, a misshapen ear:




The newborn:



An older sibling has a repaired cleft lip, cryptorchidism, deformed ears, and four toes (absent 5th toe) in both feet.



Prevalence: Very rare

Etiology:  5 sets of sibs are suggestive of autosomal recessive inheritance,[v] and only 1 occurrence of autosomal dominant postaxial acrofacial dysostosis syndrome is known.

Pathogenesis:   Polytopic field defects arising during blastogenesis1

Sonographic findings: The association of a cleft-lip/palate with micrognathia and distal limb anomalies could

Differential diagnosis: Mandibulofacial dysostosis, Treacher-Collins syndrome. Nager syndrome can be differentiated from Miller syndrome since it is pre and not post axial.

Associated anomalies:  [vi],[vii],[viii],[ix],[x]



·             Postaxial limb deficiency with absence of the fifth metacarpal or digit

·             Absent 3rd , 4th and 5th toes

·             Hypoplastic fifth digit

·             Short forearms (Ulnar hypoplasia)


·             Cleft lip/palate

·             Cup-shaped ears

·             Lower lid ectropion

·             Malar hypoplasia

·             Micrognathia


·             Midgut malrotation

·             Gastric volvulus


·             Renal anomalies

Prognosis:   Normal intelligence. Possible hearing defects.

Recurrence risk:  Mendelian


[i] Genee, E. Une forme extensive de dysostose mandibulo-faciale. J. Genet. Hum. 17: 45-52, 1969

[ii] Wiedemann, H.R: Missbildungs-Retardierungs-Syndrom mit Fehlen des 5: Strahls an Haenden and Fuessen, Gaumenspalte, dysplastischen Ohren und Augenlidern und radioulnarer Synostose. Klin. Paediat. 185: 181-186, 1973

[iii] Miller M, Fineman R, Smith, DW :  Postaxial acrofacial dysostosis syndrome. J. Pediat. 95: 970-975, 1979.

[iv] Opitz JM, Mollica F, Sorge G, Milana G, Cimino G, Caltabiano M Acrofacial dysostoses: review and report of a previously undescribed condition: the autosomal or X-linked dominant Catania form of acrofacial dysostosis. Am J Med Genet 1993 Oct 1;47(5):660-78

[v] Cacchione O, Guadagni A, Persichetti B, Logoluso G, Barbuti D. The familial Miller syndrome. Radiol Med (Torino) 1992 Nov;84(5):650-2

[vi] Ogilvy-Stuart AL, Parsons AC.Miller syndrome (postaxial acrofacial dysostosis): further evidence for autosomal recessive inheritance and expansion of the phenotype. J Med Genet 1991 Oct;28(10):695-700

[vii] Vigneron J, Stricker M, Vert P, Rousselot JM, Levy M.Postaxial acrofacial dysostosis (Miller) syndrome: a new case. J Med Genet 1991 Sep;28(9):636-8

[viii] Barbuti D, Orazi C, Reale A, Paradisi C.Postaxial acrofacial dysostosis or Miller syndrome. A case report. Eur J Pediatr 1989 Feb;148(5):445-6

[ix] Chrzanowska KH, Fryns JP, Krajewska-Walasek M, Wisniewski L, Van den Berghe H. Phenotype variability in the Miller acrofacial dysostosis syndrome. Report of two further patients. Clin Genet 1989 Feb;35(2):157-60

[x] Donnai D, Hughes HE, Winter RM. Postaxial acrofacial dysostosis (Miller) syndrome. J Med Genet 1987 Jul;24(7):422-5

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