21 Chromosome 4p– Syndrome
del(4p) syndrome, Wolf-Hirschhorn syndrome
Growth and mental retardation, microcephaly, Greek helmet facies, visceral malformations
Frequency: 1 in 50,000 newborns; 2:1 female pre- dilection
Genetics
Partial deletion of the short arm of chromosome 4;
critical band 4p16.3 (OMIM 194190); a number of patients have subchromosomal deletion; fluores- cence in situ hybridization (FISH) analysis is indicat- ed; contiguous genes are involved; 80% of deletions are paternal in origin; 10% of cases are due to parental translocation.
Clinical Features
• General growth retardation
• Mental retardation
• Microcephaly, scalp defects, high forehead
• Greek helmet facies, prominent glabella, beaked nose
• Downward slanting palpebral fissures, hypertelo- rism, iris coloboma, divergent strabismus
• Carp-shaped mouth, short philtrum, cleft lip/palate
• Micrognathia
• Low-set, simple ears
• Hypospadias, cryptorchidism
• Dimpling over shoulders, elbows, knees, and sacrum
• Congenital heart defects
• Pulmonary isomerism
• Common mesentery
• Renal hypoplasia Differential Diagnosis
• Pitt-Rogers-Danks syndrome (microdeletion 4p16.3)
Radiographic Features Skull
• Microcephaly, scaphocephaly
• Craniofacial asymmetry
• Hypertelorism
• Micrognathia
Chromosome 4p– Syndrome 630
Fig. 21.1. Patient 1, 3 months. Microcephaly, prominent glabel- la, hypertelorism, downward slanted palpebral fissures, stra- bismus, short philtrum, and low-set, simple ears
Fig. 21.2. Patient 2, 3 years. Microcephaly, prominent glabella, synophrys, large nasal bridge, upward slanted palpebral fis- sures, divergent strabismus, bilateral cleft lips, and asymmetri- cal, prominent, simple ears
Generalized Skeletal Abnormalities
• Delayed bone age Spine
• Kyphoscoliosis
• Fused vertebrae
• Bifid vertebrae Pelvis
• Small pelvis with underdeveloped pubic rami
• Separation of pubic bones
• Increased iliac angles
• Dislocated hips Extremities
• Flexion deformity of the fingers
• Clinodactyly
• Malformed halluces
• Proximal radioulnar synostosis
• Thin fibulas
• Poorly ossified middle and distal fingers and toes phalanges
• Thin diaphysis of long bones
• Talipes equinovarus Chest
• 13 pairs of ribs
• Rib anomalies
• Anomalous sternal ossification
Bibliography
Battaglia A, Carey JC, Cederholm P, Viskochil DH, Brothman AR, Galasso C. Natural history of Wolf-Hirschhorn syn- drome: experience with 15 cases. Pediatrics 1999; 103:
830–6
Johnson VP, Mulder RD, Hosen R. The Wolf-Hirschhorn (4p-) syndrome. Clin Genet 1976; 10: 104–12
Lazjuk GI, Lurie IW, Ostrowskaja TI, Kirillova IA, Nedzved MK, Cherstovoy ED, Silyaeva NF. The Wolf-Hirschhorn syn- drome II. Pathologic anatomy. Clin Genet 1980; 18: 6–12 Lurie IW, Lazjuk GI, Ussova YI, Presman EB, Gurevich DB. The
Wolf-Hischhorn syndrome. Clin Genet 1980; 17: 375–84 Wright TJ, Clemens M, Quarrell O, Altherr MR. Wolf-Hirsch-
horn and Pitt-Rogers-Danks syndromes caused by overlap- ping 4p deletions. Am J Med Genet 1998; 75: 345–50
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