American Journal of Medical Genetics 47:707-709 (1993)

Autosomal Recessive Short Stature, Robin Sequence, Cleft Mandible, Pre/Postaxial Hand Anomalies, and Clubfeet in Male Patients A. Richieri-Costa and Sonia Cristina Silveira Pereira Serv+o de GenCtica Clinica, Hospital de Pesquisa e Reabiliwcio de Les6es Ubw-Palatuis, Universidade a!e Scio Paulo, Bauru, SP, Brazil

We report on 2 unrelated Brazilian boys with the syndrome of autosomal recessive short stature, Robin sequence, cleft mandible, pre/ postaxial hand anomalies, and clubfeet. This is the first report of male patients. 0 1993 Wiley-Lisa, Inc.

KEY WORDS: acrofacial dysostosis, Robin sequence, limb anomalies, consanguinity, autosomal re- cessive inheritance

INTRODUCTION The condition reported here was described recently in

Brazilian patients [Richieri-Costa and Pereira, 19921. Consanguineous parents, recurrence in sibs, and high rate of male death suggested a sublethal autosomal re- cessive condition. This is the first report on affected male patients.

CLINICAL REPORTS Patient 1

ROS (Figs. 1A-B), male, born in 1992, was the 1st child of an 18-year-old G1 white woman and her 21-year- old nonconsanguineous husband. Pregnancy was nor- mal; no toxic, infectious, or traumatic incidents, or X-ray exposure were reported. Delivery was normal and at term. Birth weight (BW) was 3,100 g (25th centile); birth length (TBL) and OFC were not recorded. Micro- gnathia and clubfeet were noted at birth. Respiratory distress and feeding problems were noted neonatally. He has remained under medical care in our nursery since the age of 6 months with severe malnutrition. On clini- cal examination at age 8 months, weight was 4,370 g (<3rd centile), height 53 cm (3rd centile), and OFC 42.0 cm (97th centile corrected for height). He had short stature, prominent ears, retromicrognathia, micro-

Received for publication May 12,1993; revision received June 9, 1993.

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

0 1993 Wiley-Liss, Inc.

Fig, (A, B) Clinical aspects of the face of patient 1.

stomia, cleft lower alveolar ridge (Fig. 21, mildly hypo- plastic and proximally placed thumbs, mildly hypoplas- tic finger 5, radial deviation of both hands (Fig. 3A-B), and bilateral clubfeet (Fig. 4).

Roentgenograms showed midline cleft of the mandi- ble, micrognathia, hypoplastic first and fifth rays of hands (Fig. 5), and bilateral clubfeet (Fig. 6). Sono-

Fig. 2. Clinical aspects of the mouth of patient 1.

708 Richieri-Costa and Pereira

Fig. 3. (A, B) Clinical aspects of the hands of patient 1.

Fig. 5. Roentgenological aspects of the handa of patient 1. graphic examination of the kidneys and IVP were nor- mal.

Patient 2 JMMC (Figs. 7A-B), male, born in 1979, was the 8th

child of a 34-year-old G9,PS white woman and her 40- year-old consanguineous (first cousin) husband. Preg- nancy was normal; no toxic, infectious, or traumatic incidents or X-ray exposure were reported. Delivery was at term, through cesarean section. BW, TBL and OFC were not recorded. Micrognathia and clubfeet were noted at birth. Outcomes of previous pregnancies were (1) 2 normal girls and 4 normal boys, and (2) 2 female infants, dead at age 8 days and 3 months, respectively, who purportedly had the same anomalies. On clinical examination at age 13 years, height was 145 cm (<loth centile), OFC 53.5 cm (50th centile), and neuropsycho- logical development was normal. Other manifestations were short stature, apparently low-set and mildly ante- verted ears, retromicrognathia, microstomia, cleft lower alveolar ridge (Fig. 8), mildly hypoplastic 5th fingers, bilateral clubfeet, hypoplastic and proximally placed toes 1 and 5 (Fig. 91, pectus excavatum, and lumbar lordosis.

Roentgenograms showed midline cleft of the mandible with absence of the upper lateral incisors and lower incisors and canines (Fig. lo), mild hypoplasia of the 5th

Fig. 6. Roentgenological aspects of the feet of patient 1.

Fig. 7. (A, B) Clinical aspects of the face of patient 2.

Fig. 4. Clinical aspects of the feet of patient 1.

Fig. 8. Clinical aspects of the mouth of patient 2.

Fig. 9. Clinical aspects of the feet of patient 2.

Fig. 10. Orthopantomography of patient 2.

Autosomal Recessive Short Staturebbin Sequence 709

Fig. 11. Roentgenological aspects of the hands of patient 2.

Fig. 12. Roentgenological aspects of the feet of patient 2.

ray of the hands (Fig. 111, shortness of toe 1 and abnor- mally modeled metatarsals 1-5 (Fig. 12).

DISCUSSION Up to now we have studied 7 families (4 consan-

guineous/3 nonconsanguineous) with this autosomal re- cessive condition, with 15 affected patients (7 malel8 female). Eight patients are alive 6 female/2 male) and 7 are dead (5 malel2 female). Six of the 7 families live in the same area in the South of the State of SBo Paulo, and most likely they have a common ancestor. In the patients previously reported all affected males were dead, sug- gesting a sublethal recessive condition; however, the clinical signs of the patients reported here showed no evidence that male patients are more affected than females, and the initially observed deficiency of males could be from bias due to the small sample of previously reported patients.

REFERENCE Richieri-Costa A, Pereira SCS (1992): Short stature, Robin sequence,

cleft mandible, pre/postaxial hand anomalies, and clubfoot: A new autosomal recessive syndrome. Am J Med Genet 42:681-687.