American Journal of Medical Genetics 27:971-975 (1987)

Letter to the Editor: The Genee-Wiedemann Syndrome, an Acrofacial Dysostosis-Further Observation To the Editor:

In the preceding letter, Meinecke and Wiedemann comment on the paper by Robinow et al [1986], whose observations they interpret as an example of the so-called postaxial acrofacial dysostosis syndrome (POADS), a condition we prefer to call the GenCe-Wiedemann syndrome [see Lewin and Opitz, 19861. We concur with their conclusions and the diagnosis in the patient they report in their letter. Thus, the Genie- Wiedemann syndrome is an autosomal recessive multiple congenital anomalies (MCA) syndrome of acrofacial dysostosis with lower limb involvement and other anomalies that may include supernumerary vertebrae and other vertebral segmentation and rib defects, congenital heart defect (ASD, VSD), extra nipples, single umbilical artery, and absence of a hemidiaphragm. Lower limb abnormalities may be slight, ie, hypoplasia of fifth toes, but may be severe and include total absence of fibulae and polydactyly. Upper limb defects may be as severe as phocomelia with hypoplastic pectoral girdle (scapulae). Presence of mental deficiency in older individuals and slow psychomotor development in infancy and childhood of other cases suggest that the GenCe-Wiedemann syndrome may be a true MCA/MR syndrome.

Recently, G.B.S. studied a young woman at the Mayo Clinic 9 years after her older brother was first seen by the senior author at the University of Wisconsin (1965) with an MCA syndrome that could then not be diagnosed.

The propositus, J.W., was born on June 3, 1965 at 4 1 4 2 weeks of gestation with a birth weight of 3,454 g and length of 49.5 cm. This was the first pregnancy of 21- and 20-year-old parents who were nonconsanguineous. The father had had an older sib who died of spina bifida a few months after birth; otherwise the family history was unremarkable. The pregnancy was unremarkable, fetal movements were vigorous, there was no known prenatal exposure to drugs, trauma, radiation, or toxins, and delivery was spontaneous from a vertex position. The infant was in an incubator 2 days for “pulmonary congestion,” but went home with mother on day 4. A suspicion of Down syndrome was entertained on account of multiple congenital anomalies.

Received for publication January 26, 1987; revision received March 2, 1987

Address reprint requests to Dr. John M. Opitz, Shodair Genetics, Box 5539, Helena, M T 59604.

0 1987 Alan R. Liss, Inc.

972 Opitz and Stickler

Fig. 1. Hands (A and B) of patient 2 at I3%2 years

J.W. was examined at age 12 days when he was 54.6 cm long, had an OFC of almost 37 cm, and an inner epicanthic distance of 2.5 cm. The infant was found to have a striking appearance with brachycephaly, hypoplastic supraorbital ridges, very puffy eyelids, which bulged out beyond the supraorbital ridges, small nose with anteverted nostrils, microgna- thia, hypoplastic external ears which were posteriorly angulated and incompletely differentiated.

In addition, the child had brachycephaly, hypoplastic uvula, short tip of tongue bound down by the frenulum, absence of all fifth digits, simian creases, “trigger” thumbs, and absence of one flexion crease on the index fingers. Back, genitalia, chest, and cardiovascular systems were normal, and the infant had a lusty cry, pink color, good tone, and made a “bright” impression.

Roentgenologically, there was absence of the fifth ray of hands and feet; absence or failure of ossification of the middle phalanges of the second, third, and fourth digits of both feet, and of the distal phalanx of the thumbs. Vertebral column, ribs, pelvis, femora and tibiae, arm and forearm bones were normal; skull films showed micrognathia.

The infant’s chromosomes were studied twice in 1965 and both times were apparently normal.

Letter to the Editor 973

Fig. 2. Feet (A and B) of patient 2 at 13$2 years.

On a reexamination at 3 months, small palpebral fissures with mongoloid slant were recorded with normal growth and psychomotor development, but anteverted nostrils, camptodactyly of second and third fingers, “coccygeal sinus,” and bilateral mid forearm creases “halfway around the dorsal side.”

At that time it was not possible to make the diagnosis of a known entity, and in consultation with members of the University of Wisconsin Department of Medical Genetics, a low empiric recurrence risk was counseled; subsequently the parents had 2 normal boys. A follow-up letter from Dr. Frank A. Walker in Milwaukee (December 1971) stated that the propositus “has grown and been able to keep up with peers and is now doing well in school.” Mother mentioned a “micropenis” and very small testes in comparison to his 2 younger brothers.

On February 20, 1971, the parents had a similarly affected girl (M.W., patient 2) with a “boot-shaped” heart with no murmur, but some peripheral and facial cyanosis. She was admitted to Milwaukee Children’s Hospital for repair of a posterior cleft palate with oligodactyly of hands and feet, marked hypoplasia of radii and ulnae, hypoplastic, low-set ears, and slight webbing of neck. At age 13 years she was evaluated at the Mayo Clinic

974 Opitz and Stickler

Fig. 3. General appearance of patient 2 at 1 3 % ~ years.

Facial appearance of patient 2 at 1 3 % 2 years. Fig. 4.

where it was possible to make the correct diagnosis from a perusal of the Wiedemann Atlas [ 19821. Figure 1 A,B shows her upper limb anomalies.

Her left upper limb was the dominant and less severely affected upper limb. The fifth digit was absent, the rest of the hand was small with limited distal phalanx flexion and absence of flexion creases in all digits, and a reduced first web space. She had had several operations on the right hand and forearm, including releases of interdigital webs, “centralization of ulnarly deviated wrist,” rotation osteotomy of right radius, radial and ulnar osteotomy for bowing, and arthrodesis of right wrist. The right thumb was 1 cm long, the index was the longest finger on her right hand (6.5 cm), and the fourth (most ulnar) finger was 1 cm longer than the third (6 vs 5 cm). The second finger was medially, the fourth laterally rotated.

Figure 2A,B shows her feet. The fifth toes are absent, and on the right the third toe is hypoplastic and dorsally positioned. On the left she had a hallucal distal loop, on the right an open field.

Her height was 157 cm, weight 52 kg, and her blood pressure was normal (Fig. 3 ) . She was healthy, gave an appearance of normal intelligence, was neurologically normal, and was in Tanner stage 3 of pubertal development. She required speech therapy until she was in fourth grade.

Her facial appearance (Fig. 4) was exactly like that of her brother with short upslanting palpebral fissures, relatively flat philtrum, and somewhat short midface.

This case documents further variability in the Gente-Wiedemann syndrome and suggests that mental retardation in this condition may be related to the severity of the cranial neural crest defect (mandibulofacial dysostosis).

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ACKNOWLEDGMENTS

1 am most grateful to LaVelle M. Spano for expert secretarial collaboration, and to the State of Montana for support under HB430.

REFERENCES

Lewin SO, Opitz J M (1986): Fibular a/hypoplasia: Review and documentation of the fibular developmental field. Am J Med Genet Suppl 2:215-238.

Meinecke P, Wiedemann H-R (1987): Letter to the editor: Robin sequence and oligodactyly in mother and son-Probably further example of the postaxial acrofacial dysostosis syndrome. Am J Med Genet 27:953-956.

Robinow M, Johnson GF, Apesos J (1986): Robin sequence and oligodactyly in mother and son. Am J Med Wiedemann H-R, Grosse F-R, Dibbern H (1982): Das characteristische Syndrom-Blickdiagnose van

Syndromen; Ein Atlas fur Klinik und Praxis. Stuttgart: F.K. Schattauer, p 316.

John M. Opitz Gunnar B. Stickler Shodair Children’s Specialty Hospital Helena, Montana The Universities of WushingtonlSeattle

Montana State University, Bozeman (J.M.O.) Department of Pediatrics Mayo Clinic, Rochester Minnesota (G.B.S.)

and Wisconsin/Madison

Edited by James F. Reynolds