Postaxial acrofacial dysostosis: Report on two patients

American Journal of Medical Genetics 44:274-279 (1992)

Brief Clinical Report

Postaxial Acrofacial Dysostosis: Report on Two Patients

Sonia C.S. Pereira, Christiane M.G. Rocha, M.L. Guion-Almeida, and A. Richieri-Costa Servico de Gendtica Clinica, Hospital de Pesquisa e Reabilitqcio de LesBes Labw-Palatais, Universidade de Scio Paulo, Bauru, SP, Brazil

We report on 2 patients with the postaxial acrofacial dysostosis (AFD) syndrome. One patient was an isolated case; the other had an equally affected brother previously de- scribed [Richieri-Costa and Guion-Almeida, 19891. Recurrence in sibs suggests autosomal recessive inheritance. o 1992 WiIey-Liss, Inc.

KEY WORDS: postaxial acrofacial dysostosis, Genee-Wiedemann syndrome, Miller syndrome, autosomal recessive inheritance

INTRODUCTION Most reported cases of AFD syndrome have been spo-

radic [Birch-Jensen, 1949; GenBe, 1969; Wiedemann, 1973; Brunoni et al., 1987; Meinecke and Wiedemann, 1987; Vigneron et al., 19911, but autosomal recessive [Fineman, 1981, Opitz and Stickler, 1987; Ogilvy- Stuart and Parsons, 19911 and autosomal dominant inheritance [Robinow et al., 19861 have been reported. Here we report on an isolated case and on a recurrence in a sister of a patient previously reported by Richieri- Costa and Guion-Almeida [19891.

CLINICAL REPORTS Patient 1

SCPA (Fig. 1A-C) was born in 1989. She is the first child of a 19-year-old normal mother and her nonconsanguineous 27-year-old normal husband. Pregnancy was normal with absence of exposure to toxins, infections, traumatic incidents, or radiation. Delivery was through cesarean section at term. BW was 3,500g (50th centile), TBL and OFC were not recorded. Limb anoma-

Received for publication April 8, 1991; revision received Febru- ary 27, 1992.

Address reprint requests to A. Richieri-Costa, Servico de Genet- ica Clfnica, HPRLLP-USP, P.O. Box 620,17043 Bauru, SP, Brazil.

0 1992 Wiley-Liss, Inc.

lies were soon noted at birth. Neuropsychological development was normal.

Clinical examination at age 22 months showed height of 72 cm (< 3rd centile), weight of 7,050 g (< 3rd centile), and OFC of 45 cm (50th centile) (both corrected for height). She presented short stature, round face, deep- set eyes, mild hypoplasia of the malar bones, puffy cheeks, limited movement of the temporo-mandibular joint, micrognathia, submucous cleft palate, cleft uvula, short and webbed neck, pectus escavatum, hypoplastic forearms, limited movement of the left elbow, ulnar deviation of the hands and wrists (Fig. lA), absence of the 5th rays, polysyndactyly of the 2nd finger and campto- dactyly of the fingers 2-4, at left (Fig. 2), tibia1 deviation of toes 4, shortness of the 5th toes, toraco-lumbar scoliosis.

Roentgenograms showed: hypoplastic spinous proc- ess of the first cervical and fusion of the spinous proc- ess of the 2nd and 3rd cervical vertebrae, humero- radial synostosis, bowed and short radius, hypoplastic ulna, hypoplastic metacarpals, duplication of the mid- dle and distal phalanges of finger 2, at left, mild hypoplasia of the right radius, absence of the 5th ray bilaterally (Figs. 3, 41, thoraco-lumbar scoliosis.

Patient 2 JS (Fig. 51, a girl, was born in 1989 to a G6P4A2 26-

year-old mother and her nonconsanguineous 29-year- old husband. The outcomes of previous pregnancies re- sulted in 2 first trimester abortions, 2 normal girls, and an equally affected boy, age 8 years. Pregnancy was normal with absence of exposure to toxins, infections, traumatic incidents, or radiation. Delivery was through cesarean section at term. BW 3,800. TBL and OFC were not recorded. Cleft palate and limb anomalies were noted at birth. Neuropsychological development was normal.

Clinical examination at age 18 months showed length: 77 cm (< 25th centile), weight: 8.2 kg (< 3rd centile), OFC 44.5 cm (< 25th centile), inner canthal distance 2.6 cm (50th-75th centile), outer canthal distance 6.7 cm (25th centile), palpebral fissures 1.7 cm (< 3rd centile), prominent supraorbital ridges, deeply set eyes, upward

Postaxial Acrofacial Dysostosis 275

Fig. 1. A-C. General, frontal, and lateral views of the patient 1.

Fig. 2. A-B. Clinical aspects of the hands of the patient 1

slant of the palpebral fissures, small and S-shape palpebral fissures, scarce eyelashes in the lower lids, me- dian cleft of the soft palate, micrognathia, mild malar hypoplasia, hypoplastic forearms (markedly at left), ulnar deviation of the hands and wrists, absence of the 5th rays, hypoplasia of the 1st and 2nd fingers at left with proximal cutaneous syndactyly, hypoplastic thumb at left (Fig. 61, absence of the 5th rays, syndactyly between toes 1-2, and hypoplastic toe 3 at left (Fig. 7). Der- matoglyphics are shown in Table I.

Roentgenograms showed bilaterally hypoplastic, bowed and abnormally modeled radii and ulnae, absence of the 5th ray, hypoplastic rays 1-2, markedly at left (Fig. 81, and hypoplastic metatarsal 3-4 at left, hypoplastic phalanges, absence of the 5th rays (Fig. 9).

DISCUSSION During the last 20 years, the 20 reports (including the

present one) on Genbe-Wiedemann syndrome brought

Fig. 3. A-B. Radiological aspects of the left upper limb of the patient 1.

the overall number of affected patients to 27 (Tables 11, 111).

Most cases have been sporadic [Genke, 1969; Wied- emann, 1973; Pashayan and Feingold, 1975; Smith and Jones, 1975; Wildervanck, 1975; Miller et al., 1979; Poi- ssonnier et al., 1983; Donnai et al., 1987; Meinecke and Wiedemann, 1987; F’ryns and Van den Berghe, 1988; Hauss-Albert and Passarge, 1988; Barbuti et al., 1989; Chrzanowska et al., 1989; Richieri and Guion-Almeida,

276 Pereira et al.

Fig. 4. patient 1.

A-B. Radiological aspects of the right upper limb of

Fig. 6. Patient 2: (A), right arm (B) left arm, (C) hands.

Fig. 5. A,B. Face of patient 2.

1989; Vigneron et al., 19911. Recurrence in sibs (ob- served in 4 instances) [Fineman, 1981; Opitz and Stick- ler, 1987; Ogilvy-Stuart; Parsons, 1991; and patient 2 of the present report] and vertical transmission (in one instance, mother and son) [Robinow et al., 19861 suggests genetic heterogeneity, and the report of patients with severe postaxial limb involvement related with the Genee-Wiedemann syndrome, could suggest clinical heterogeneity [Rodriguez et al., 19901, in spite of the broad spectrum of the postaxial AFD syndrome [Opitz and Stickler, 1987; Ogilvy-Stuart and Parsons, 19911.

In the present report the occurrence of an affected girl (patient 2) with an equally affected brother, previously reported by Richieri-Costa and Guion-Almeida [19891,

Fig. 7. Clinical aspects of the feet of the patient.


Fig. 8. Radiological aspects of the upper limbs of the patient.

Fig. 9. Radiological aspects of the lower limbs of the patient.

TABLE I. Dermatoglyphic Patterns of Patient 2 and Her Affected Brother*

I I1 111 IV V count count count count a-b ridge b-c ridge c-d ridge A'-d ridge Digits

Patient 2 ? ? L' L' Left

Right L" A L" L" Affected brother Left A L" A W Right A L' W W *Patient 2 (the proposita) had hypoplastic creases. Her brother presented as additional findings: triradii t distally placed, acessory triradii c, vestigial (V) pattern in the thenar region, hypothenar pattern (L"), verticalization of the line T toward the 2nd interdigital area.

- - - - - - - - - -

- 43 32 d absent d absent - 45 c absent d absent d absent

TABLE 11. Main Clinical Data Present in Patients With the GenBe-Wiedemann Syndrome: Isolated Cases' References 1 2 3 4 5 6 7 8 8 8 9 10 11 12 12 13 Present Report

C1 C1 C1 C1 C1 C1 C1 C1 C2 C3 C1 C1 C1 C1 C2 C1 Patient 1 Sex M M M M M M M F M F M M M F M M F Malar hypoplasia + - + + + + + + + + + + + + + + + Micrognathia + - + + + + + + + + + - + + + + + Antimongoloid slant + + + + + - Lower lid ectropion + + + + + + + + + + - + + + + + Cleft palate Cleft lip Ear anomalies + + + + + + + + - + - - + + + + Deafness - + - + - CHD Extra nipples - + + + + - - + + NHypoplasia first ray - - + - + + + - - - + - + + + + NHypoplasia fifth ray + + + + + + + + + + + + + + + + + Radial anomalies - + + + - + + + + + + - + + - - + Ulnar anomalies + + + + - + + + + + + - + + - - + Radio-ulnar synostosis + - - - + + - - + NHypoplasiafirst ray - - - - - - - - - - - - NHypoplasia fifth ray + + + + + + - + + + + + + + + + Tibia1 anomalies - - + - - - + - - - - - + - - Fibular anomalies - - + - - - + - - - - - + - -

+ - - - - - + - + + -

+ + + + + - - + + + + + + - + + + - - - + + - - - - - - - - - - -

-

- -

- - - - - + + + + -

Upper limbs

Lower limbs + - - -

-

- -

*Legend C = Case; + = present; - = absent; F = female; M = male; CHD = congenital heart disease; 1 = GenBe, 1969; 2 = Wiedemann, 1973; 3 = Pashayan and Feingold, 1975; 4 = Wildervanck; 5 = Smith and Jones, 1975; 6 = Miller et al., 1979; 7 = Poissonnier et al., 1983; 8 = Donnai et al., 1987; 9 = Mainecker and Wiedemann, 1987; 10 = Fryns and Van den Berghe, 1988; 11 = Hauss-Albert and Passarge, 1988; 12 = Chrzanowska et al., 1989; 13 = Vigneron et al., 1991.

TAB

LE 1

11.

Mai

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ata

Pres

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the

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Inh

erita

nce

Aut

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al

Dom

inan

t R

ichi

eri-

Cos

ta

Mill

er

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l.,

1979

c

2

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on-

Fine

man

, O

pitz

and

Stic

kler

, A

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da,

1981

19

87

1989

c1

c1

c2

c1

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gilv

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uart

and

Pa

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s, 1

991

c1

C2

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M

alar

hyp

opla

sia

Mic

rogn

athi

a A

ntim

ongo

loid

sla

nt

Low

er li

d ec

tropi

on

Cle

ft p

alat

e C

left

lip

Ear

ano

mal

ies

Dea

fnes

s C

HD

E

xtra

nip

ples

U

pper

lim

bs

AlH

ypop

lasi

a fi

rst r

ay

AlH

ypop

lasi

a fi

fth

ray

Rad

ial a

nom

alie

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lnar

ano

mal

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Rad

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syn

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sis

Low

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A

/Hyp

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firs

t ra

y A

lHyp

opla

sia

fift

h ra

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bia1

anom

alie

s

F + + + + + + + + + + + + -

-

-

- + -

+ + + + + -

M + + + + + + + + - + + + + + + + -

Inhe

rita

nce

Pres

ent

Rep

ort

Rob

inow

et a

l.,

Pati

ent

1986

2

c1

c2

-

-

-

Fibu

lar

anom

alie

s -

-

-


in mother and son. Probably a further example of the postaxial acrofacial dysostosis syndrome. Am J Med Genet 27:953-956.

Miller M, Fineman R, Smith DW (1979): Postaxial acrofacial dysostosis syndrome. J Pediatr 95970-975.

Ogilvy-Stuart AL, Parsons AC (1991): Miller syndrome (postaxial acrofacial dysostosis): Further evidence for autosomal recessive inheritance and expansion of the phenotype. J Med Genet 28695-700.

Opitz JM, Stickler GM (1987): The GenBe-Wiedemann syndrome, an acrofacial dysostosis: Further observation. Am J Med Genet

Pashayan H, Feingold M (1975): Case report 28, patient 2. Synd Ident

Poissonnier M, Neuville V, Petit Ph, Busuttil R (1983): Dysostose mandibubfaciale et ulno-fibulaire lethale. Ann Pediatr

Richieri-Costa A, Guion-Almeida ML (1989): Postaxial acrofacial dysostosis: Report of a Brazilian patient. Am J Med Genet 33:447-449.

Robinow M, Johnson GF, Apesos J (1986): Robin sequence and oligodactyly in mother and son. Am J Med Genet. 25:293-297.

Rodriguez JI, Palacios J, Urioste M (1990): New acrofacial dysostosis syndrome in 3 sibs. Am J Med Genet 35484-489.

Smith DW, Jones KL (1975): Case report 28, patient 1. Synd Ident

Vigneron J , Stricker M, Vert P, Rousselot JM, Levy N (1991): Postaxial acrofacial dysostosis (Miller) syndrome: A new case. J Med Genet 28:636-638.

Wiedemann HR (1973): Missbildungs-Retardierungs-Syndrom mit Fehlen des 5 Strahls an Handen and Fussen. GaumensDake, dvspla-

2T971-975.

3:9-10.

30~713-717.

3:7-8.

documents the autosomal recessive pattern of inheritance of this syndrome.

REFERENCES Barbuti D, Orazi C, Reale A, Paradisi C (1989): Postaxial acrofacial

dysostosis or Miller syndrome. Eur J Pediatr 148:445-446. BirchJensen A (1949): Congenital deformities of the upper extremi-

ties. Domus Biologiae Humanae, Universitatis Hafniensis. An- delsbogirykkeriet i Odense and Det danske Forlag, 285 pp.

Brunoni B, Guidugli-Net0 J , Chedick ES, Borovic CL (1987): Acrofacial dysostosis: A new type? Rev Bras Genet 10353-360.

Chrzanowska KH, Fryns JP, Krajewska-Walasek M, Wisniewski L, Van den Berghe H (1989): Phenotype variability in the Miller acrofacial dysostosis syndrome. Report of two further patients. Clin Genet 35157-160.

Donnai D, Hughes HE, Winter RM (1987): Postaxial acrofacial dysostosis (Miller) syndrome. J Med Genet 24:422-425.

Fineman RM (1981): Recurrence of the postaxial acrofacial dysostosis syndrome in a sibship: Implications for genetic counselling. J Pedi- atr 98:87-88.

Fryns JP, Van den Berghe H (1988): Acrofacial dysostosis with postaxial limb deficiency. Am J Med Genet 29205-208.

Genee E (1969): Une forme extensive de dysostose mandibulo-faciale. J a n & Hum 17:45-52.

Hauss-Albert H, Passarge E (1988): Postaxial acrofacial dysostosis syndrome with microcephaly, seizures and profound mental retar- dation. Am J Med Genet 31:701-703.

Meinecke P, Wiedemann HR (1987): Robin sequence and oligodactyly

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Postaxial acrofacial dysostosis: Report on two patients