Short rib-polydactyly syndrome (SRPS) with anencephaly and other central nervous system anomalies: A new type of SRPS or a more severe expression of a known SRPS entity?

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  • American Journal of Medical Genetics 4R782-787 (1993)

    Short Rib-Polydactyly Syndrome (SRPS) With Anencephaly and Other Central Nervous System Anomalies: A New Q p e of SRPS or a More Severe Expression of a Known SRPS Entity? Maria-Luisa Martinez-Frias, Eva Bermejo, Miguel Urioste, Javier Egues, and Jose A. Lopez Soler ECEMC Coordinating Group: ECEMC and Departamento de Farmacologia (M. -L.M. -F.) and ECEMC and Hospital Universitario San Carlos (M.U.), Facultad de Medicina (E.B.), Universidad Complutense de Madrid; and ECEMC Peripheric Group: Servicio de Pediatria, Hospital Virgen del Camino, Pamplona (J.E.); Servicio de Pediatria, Hospital Rafael Mendez, Lorca, Murcia (J.A.L.S.), Spain

    We describe two patients with short rib-poly- dactyly syndrome (SRPS) from two unrelated Spanish families. These patients present clini- cal and radiological characteristics that over- lap those of the different established types of SRPS. In addition, one patient had anenceph- aly and the other patient had severe brain abnormalities with a family history of an older sister with anencephaly, and a brother diag- nosed with SRPS. This second family is inter- esting in that the two affected brothers pres- ent with different clinical and radiological findings; for example, one had ovoid tibiae and the other did not. This particular family shows that intrafamiliar variation is also ob- served within SRPS.

    It remains unsettled whether these cases might be considered a new type of SRPS or a variant of an established entity or whether the differences between the SRPS represent variability or heterogeneity. Molecular studies may answer this question in the near future. 0 1993 Wiley-Liss, Inc.

    KEY WORDS: short rib-polydactyly syn- drome, Saldino-Noonan, type I SRPS, Majewski, type I1 SRPS, Verma-Naumoff, type I11 SRPS, Beemer- Langer, type IV SRPS.

    Received for publication April 5, 1993; revision received April 20, 1993.

    Address correspondence to Dr. Maria-Luisa Martinez-Frias, ECEMC, Facultad de Medicina, Universidad Complutense, 28040 Madrid, Spain.

    0 1993 Wiley-Liss, Inc.

    INTRODUCTION Brain anomalies in the group of short rib-polydactyly

    syndromes (SRPSs) are virtually restricted to Type I1 SRPS (Majewski) and consist of pachygyria, small vermis, and absence of olfactory bulbs [Majewski et al., 1971; Chen et al., 19801. In 1982, Nivelon-Chevalier et al. considered their patient with cebocephaly as an exam- ple of the Majewski type of SRPS. However, Gorlin et al. [19901 stated: We cannot classify the infant with a Majewski-like syndrome and cebocephaly. In 1991 Yang et al. published a patient with Beemer-Langer or Type IV SRPS with hydrocephaly and possible holoprosenceph- aly. More recently Tsai et al. [19921 published a SRPS child with encephalocele, concluding that the case could be an atypical form of Type I1 SRPS or another variant of Beemer-Langer or Type IV SRPS.

    We report two new SRPS cases with severe brain anom- alies including anencephaly which, as far as we know, has not been described in any type of SRPS. These cases were identified through the Spanish Collaborative Study of Congenital Malformations (ECEMC) [see Martinez- Frias et al., 1991 for ECEMC methodology].

    CLINICAL REPORTS Patient 1 (304-51)

    The propositus, a male, was stillborn at 36 weeks of gestation. The 34-year-old mother and 35-year-old father were not consanguineous, and the family history was unremarkable. The mother (G3P1) had two spontaneous abortions and surgery for an ovarian cyst 4 years before becoming pregnant with the propositus. She was being treated for menstrual irregularities with oral contracep- tives during the periconceptional period, and with pro- gestins from the 2nd to the 4th month of pregnancy. She had taken multivitamin supplements in the 3rd month. There were no other exposures, and the pregnancy was complicated only by polyhydramnios.

    The child weighed 1,580 g (

  • SRPS and CNS Anomalies 783

    TABLE I. Non-Radiologic Diagnostic Criteria for the Four Forms of SRPS and Comparison With Our Cases

    External appearance Cleft upper lip Reaxial polydactyly Postaxial polydactyly Syndactyly Omphalocele/umbilical

    hernia Systemic abnormalities CNS

    Holoprosencephaly Hydrocephaly NTD

    Hypopl. epiglottis Urinary tract anom.

    Renal agenesis Genital abnormalities Other Pol yh ydramnios Oligohydramnios Inheritance Consanguinity and/or

    affected sib Normal karyotype Sex ratio (M:F) Sex

    SRPS I Saldino Noonan

    - - + + -

    - - - -

    + + + + + + +

    AR

    4:9

    SRPS I1 Majewski

    + + + + -

    1 caseb +?d +?f + + + +

    -

    -

    AR + + 1:l

    SRPS I11 Verma

    Naumoff

    Pseudocleft

    + + -

    -

    + + +

    AR

    + 5:3

    SR(P)S IV

    Beemer Langer

    + 1 case'

    + + -

    +?'

    +?f + a, C. e

    - + + +

    -

    - AR? + + 8:5

    Present cases

    Sib of 30(-5) 15(-23) 15(-23)

    + + + + + + + + + + ?

    -

    - - -

    ? ?

    Anencephaly ? ? ? + + -

    -

    ?

    M -

    + + - - - - + ? ?

    sib

    ?

    M -

    a Described by Hennekam [19911.

    'Published by Yang et al. [19911. Reported by Nivelon-Chevalier et al. [19821.

    Rewrted bv Sharma et al. 119921. De'scribed 6y Lin et al. [19911. Tsai et al. [19921.

    ings of edema, anencephaly, bilaterally cleft upper lip, short limbs, pre- and post-axial polydactyly of the hands and feet, syndactyly, and sexual ambiguity.

    Radiological studies (Table 11, Fig. 2) showed very short ribs and long tubular bones, bowed ulnae and hypoplastic radii, inadequately ossified, small vertebral bodies with coronal clefts, and small abnormally con- toured iliac bones with horizontal, trident-shaped ace- tabular margins. There were longitudinal metaphyseal spurs in both femora and humeri. The tibiae were very short, but longer than the fibulae and not ovoid shaped. Corticomedullary differentiation was good.

    Chromosome studies and autopsy were not performed.

    Patient 2 (154-231) The propositus, a stillborn male, was the 4th preg-

    nancy of a 30-year-old mother and a 35-year-old father, both healthy and non-consanguineous. The infant was delivered, in 1985, by cesarean section at 36 weeks of gestation because of severe polyhydramnios and ultra- sonographic and radiologic diagnoses of anomalies. The birth weight was 2,920 g (2540th centile). The mother drank a glass of wine daily; there were no other expo- sures during pregnancy.

    At birth (Table I, Fig. 3a-d) the fetus had deep-set eyes (Fig. 3a), micrognathia, redundant skin on the neck (Fig. 3b), short limbs, pre- and post-axial polydactyly of

    the hands (Fig. 3c), and preaxial polysyndactyly of the feet (Fig. 3d), narrow chest, and hypogenitalism.

    Radiologic studies showed (Table 11, Fig. 4) poor ossi- fication, coronal clefts in some vertebrae, short and hori- zontal ribs, minimal bowing of both femora, ovoid tibiae, abnormal iliac bone contour, and trident-shaped lower margins of the pelvis. There were some longitudinal metaphyseal spurs (Fig. 5a,b). Corticomedullary differ- entiation was good.

    Autopsy confirmed pulmonary hypoplasia, agenesis of the cerebellum, single cerebral ventricle, agenesis of the olfactory bulbs and tracts, agenesis of the corpus callosum, hydrocephaly (Table I), and hypoplasia of the adrenal glands.

    Chromosomal analysis was not performed, and the karyotypes of the parents were normal.

    The first pregnancy of this couple ended in 1977 in a liveborn female who was described as having anen- cephaly, and about whom there is no further informa- tion. The second pregnancy was a male born in 1978 at 39 weeks of gestation, who was reported as having SRPS and dying 30 minutes after birth. Autopsy stated that the baby had (Tables I and 11) flat occiput, cleft lip and palate, low-set ears, postaxial polydactyly of the hands and preaxial polydactyly of the feet, narrow chest, short ribs, and mild shortness of the lower limbs. Radiologic report described short ribs, relatively short tibiae longer

  • 784 Martinez-F'rias et al.

    Fig. 1. Clinical appearance of patient 1. Fig. 2. Radiograph of patient 1.

    than his fibulae and not ovoid in shape (Table 11). The autopsy also documented dehiscent cranial sutures, ab- sence of olfactory tracts, single cerebral ventricle, hy- drocephaly, pulmonary hypoplasia, open ductus a r k - riosus, and undescended testes (Table I). The third baby, born in 1981, was a normal male.

    DISCUSSION Although the clinical and radiological findings of the

    different types of lethal SRPS strongly overlap, most of the authors agree that the Majewski type (type 11) is clearly distinguishable from types I and I11 [Sillence, 1980; Jones, 1989; Gorlin et al., 19901; however, discrim-

    TABLE 11. Radiolopic Diamostic Criteria for the Four Forms of SRPS and ComDarison With Our Cases

    ~~

    Short cranial base Macrocephaly Flat occiput High clavicles Rounded scapulae Vertebral anomalies Pelvic abnormalities

    abnormal contour flat acetabulum trident shaped

    Tibiae longer than fibulae Ovoid tibiae Bowed femora Good corticomedullary differentiation Metaphyseal spurs

    longitudinal

    SRPS I Saldino SRPS I1 Noonan Majewski

    SRPS 111

    Verma Naumoff

    SR(P)S IV

    Beemer Langer

    ? + ? + + + +

    -t

    + +

    Min. -

    Present cases

    Sib of 30(-5) 15(-23) 15(-23)

    ? ? ? ? ?

    ? ? + ? ?

    -

    - n

    + + +

    -

    + + + + + + + + +

    -

    -

  • Fig. 3. Patient 2. a: Clinical appearance; b: lateral view; c: polydactyly of hands; d preaxial polysyn- dactyly of feet.