1991-02-15-13 Dyssegmental dysplasia of the Silverman-Handmaker type © Joffe www.thefetus.net/
Dyssegmental dysplasia of the Silverman-Handmaker type
Gary M. Joffe, MD*, Luis A. Izquierdo, MD, Gerardo O. Del Valle, MD, George Gilson, MD, James Smith, MD, Molly S. Chatterjee, MD, and Luis B. Curet, MD
Synonyms: Anisospondilic camptomicromelic dwarfism.
Prevalence: 20 cases since 1969.
Definition: Lethal form of micromelic dwarfism characterized by disorganization of the vertebral bodies, camptomelia and micromelia.
Etiology: Probably autosomal recessive. Patients of Hispanic origin are well represented in the Silverman-Handmaker variety.
Pathogenesis: Disorganization of growth plate, large calcospherites, and haphazard arrangement of collagen fibers on scanning electron microscopy of bone.
Associated anomalies: Cephalocele, mid-facial defects, small orbits, cleft palate, short neck, elongated scapulae, abnormal size, shape and ossification of the acromion, coracoid process, and body of the scapulae, cardiac defects, and hydronephrosis.
Differential diagnosis: Fibrochondrogenesis, chondrodysplasia punctata and Weissenbacher- Zweymuller syndrome.
Recurrence risk: Mendelian inheritance.
Management: As for diseases with fatal outcome.
MESH Bone-Diseases,-Developmental-diagnosis; Dwarfism-genetics; -diagnosis BDE 2935 MIM 26250 POS 3207 ICD9 756.9-259.4 CDC 756.930
* Address correspondence to: Gary M. Joffe, MD, University of New Mexico, School of Medicine, Dept. of Ob-Gyn. 2211 Lomas Blvd., NE, Albuquerque, NM 87131-5286 Ph: 505-277-8381 (voice), 277-7621 (fax)
The antenatal diagnosis of lethal, short-limbed dyssegmental dysplasia of the Silverman-Handmaker type has recently been reported by our institution.1 Dyssegmental dysplasia is characterized by marked disorganization of the vertebral bodies, bowing of the long bones (camptomelia) and micromelia. Other findings may include cephalocele, mid-facial defects, cleft palate, cardiac defects, and hydronephrosis. Inheritance is probably autosomal recessive. Patients of Hispanic origin seem to be heavily represented in the Silverman-Handmaker variety of the disease.1
At our institution we have recently diagnosed and delivered another patient with the Silverman- Handmaker type of dyssegmental dysplasia.
The patient is an 18 year old unmarried female of Hispanic/German origin. She presented to the antenatal testing unit at our institution at seventeen weeks estimated gestational age. She was a referral from her primary care physician for evaluation of “intrauterine growth retardation.”
Ultrasonographic findings at this time included marked disorganization of the vertebral bodies, a shortened femur demonstrating camptomelia, and a posterior cephalocele (fig. 1-2).
Fig. 1: Ultrasound of the femur demonstrating marked bowing of the diaphysis (camptomelia). Right: Ultrasonographic demonstration of disorganization of the spinal column. Note the haphazard arrangement of the vertebral bodies in the lumbar region.
Fig. 2: Ultrasound of the calvarium demonstrating prominent posterior cephalocele.
The diagnosis of dyssegmental dysplasia was made, and the patient was offered genetic counseling. She was counseled that this disease is always lethal and was offered pregnancy termination. She declined and opted to continue the pregnancy.
Further history revealed no substance abuse, exposure to toxins, or family history of consanguinity. Serial ultrasounds were performed throughout the gestation and revealed hydronephrosis in addition to the previously mentioned findings. Two days subsequent to the last ultrasound at 36 weeks of gestational age, the patient reported no fetal movement. An intrauterine fetal demise was confirmed. The patient was induced and delivered a stillborn female infant weighing 1720g.
Autopsy findings confirmed micromelic dwarfism with a flattened mid-facies and a posterior cephalocele (fig. 3).
Fig. 3: Micromelic female infant after delivery (left and middle). Note the flattened mid-facies and equinovarus deformity. Posterior view demonstrating posterior cephalocele, moderate hirsuitism, and equinovarous deformity.
Fig. 4: Radiograph at autopsy demonstrating marked disorganization of the vertebral bodies. See text for further description of bony deformities.
Radiographic findings at autopsy demonstrated marked vertebral disorganization, short humeri, and femurs with splayed metaphyses. Also noted was abnormal angulation of the bones of the distal extremities (fig. 3 right).
The antenatal diagnosis of short-limbed dwarfism is usually made in one of two clinical situations: the patient is referred for ultrasound secondary to a family history of dwarfism, or routine exam reveals a femur measuring less than the 5th percentile for gestational age. Rhizomelic dwarfism is characterized by shortening of proximal long bones; micromelic dwarfism, exemplified by dyssegmental dysplasia, reveals abnormalities in all bony structures.
Izquierdo1, Aleck2, and others have described the typical findings of dyssegmental dysplasia which include micromelic dwarfism, disorganization of vertebral bodies, cephalocele, small orbits, mid-facial flattening, cleft palate, short neck, elongated clavicles, and alterations in the size, shape and ossification of the acromion, coracoid process, and body of the scapulae. Usually present is the finding of hydroureter.
Aleck2 and others have described the less severe, although ultimately fatal form of dyssegmental dysplasia known as the Rolland-Desbuquois variety. Most affected infants survive the neonatal period, but succumb by the age of three years. This variety of the disease has not yet been described in the Hispanic population.
The differential diagnosis includes fibrochondrogenesis, chondrodysplasia punctata and Weissenbacher-Zweymuller syndrome.
Fibrochondrogenesis is characterized by limb and vertebral deformities including shortened dumbbell-shaped metaphyses and pear-shaped vertebral bodies3. The short limbs noted in fibrochondrogenesis are in a proximal or rhizomelic pattern. This is in contrast to dyssegmental dysplasia which is characterized by micromelia or disproportionate shortening of the entire extremity.
Chondrodysplasia punctata is typified by vertebral bodies with coronal clefts, metaphyseal splaying and stippled epiphyses. The ultrasound diagnosis is reported elsewhere in this issue3, and the rhizomelic, potentially lethal variety has been diagnosed using radiography4.
The final diagnosis of short-limb dwarfism often requires analysis of the pathologic specimen. For example, scanning electron microscopy has been used to demonstrate that growth plate morphology, cartilage calcification, bone morphology and collagen within resting cartilage are all more extensively abnormal in the Silverman-Handmaker form of the disease than in the Rolland-Desbuquois variety2.
1.Izquierdo LA, Kushnir O, et al. Antenatal ultrasonic diagnosis of dyssegmental dysplasia: a case report. Prenatal Diagnosis (in press)
2.Aleck KA, Grix A, et al. Dyssegmental dysplasias: clinical, radiographic, and morphologic evidence of heterogeneity. Am J Med Genetics 27:295-312, 1987
3. Furness ME, Haan EA, Hopkins PB et al: Chondrodysplasia punctata, mild symmetric type with echogenic coccyx in a 15 week fetus. The Fetus 1:1 7565-1, 1991
4. Romero R, Pilu G, Jeanty P, et al: Prenatal diagnosis of congenital anomalies. Norwalk, Connecticut: Appleton & Lange, 1988, pp 339-340; 349-351