92 Seckel Syndrome

92 Seckel Syndrome

Seckel Syndrome 863

Bird-headed dwarfism

Dwarfism, small head, large eyes, beaked nose, mental retardation

Frequency: Rare. Overdiagnosed.

Genetics

Autosomal recessive (OMIM 210600). One form of Seckel syndrome can be caused by mutation in the gene encoding ataxia-telangiectasia and RAD3-relat- ed protein, which maps to chromosome 3q22.1-q24.

Other loci for Seckel syndrome have been mapped to chromosomes 18p11-q11 and 14q.

Clinical Features

• Low birth weight-type dwarfism (approximately 1540 g at term)

• Marked postnatal growth retardation (on average, 7 SD below the mean)

• Severe microcephaly, receding forehead

• Narrow face, with relatively large eyes, a promi- nent beaklike nose, and micrognathia

• Other craniofacial features may include: facial asymmetry, down-slanting palpebral fissures, and highly arched or cleft palate

• Dental anomalies (enamel hypoplasia, crowded teeth, malocclusion)

• Dysplastic, low-set ears

• Joint dislocations

• Moderate to severe mental retardation (IQ below 50 in half of the patients)

• Cryptorchidism, clitoromegaly, hypospadias

• CNS anomalies (callosal agenesis, cerebellar hypo- plasia, pachygyria, enlarged basal ganglia, arach- noid cysts)

Differential Diagnosis

• Osteodysplastic primordial dwarfism,types I and II

• Other syndromes with growth deficiency and mi- crocephaly (Dubowitz syndrome, fetal alcohol syndrome, trisomy 18 syndrome, de Lange syn- drome, Bloom syndrome, Fanconi syndrome)

Radiographic Features Skull

• Microcrania, flattened frontal bones, prominent occiput

• Synostosis of cranial sutures (50%)

• Hypertelorism

• Hypoplasia of maxilla and mandible Generalized Bone Defects

• Delay in skeletal maturation Hands and Feet

• Short digits

• Clinodactyly of 5th fingers

• Ivory epiphyses, cone-shaped epiphyses of proxi- mal phalanges

Spine

• Kyphoscoliosis

• Platyspondyly Pelvis

• Narrow ilia, shallow acetabula, coxa valga Joints

• Multiple dislocations (hip, knee, elbow)

Fig. 92.1. Patient 1, age 1 month. Severe microcephaly, large S

eyes, receding forehead with prominent metopic suture, nar- row face, beak-like protrusion of nose, and micrognathia

Bibliography

Harper RG, Orti E, Baker RK. Bird-headed dwarfs (Seckel’s syndrome): a familial pattern of developmental, dental, skeletal, genital and central nervous system anomalies.

J Pediatr 1967; 70: 799–804

Majewski F, Goecke T. Studies of microcephalic primordial dwarfism I: approach to a delineation of the Seckel syn- drome. Am J Med Genet 1982; 12: 7–21

McKusick VA, Mahloudji M, Abbott MH, Linbenberg R, Kepas D. Seckel’s bird-headed dwarfism. N Engl J Med 1967; 277:

279–86

Seckel HPG. Bird-headed dwarfs: studies in developmental anthropology including human proportions. Charles C.

Thomas, Springfield, Ill., 1960

Thompson E, Pembrey M. Seckel syndrome: an overdiagnosed syndrome. J Med Genet 1985; 22: 192–201

Seckel Syndrome 864

Fig. 92.2 a, b. Patient 2, age 4 days. Scaphocephaly with flat, receding frontal bones; prominent occiput; wide open metopic suture; hypertelorism; and hypoplastic maxilla and mandible

a b

Seckel Syndrome 865

S

Fig. 92.3. a, b Patient 2, age 4 days. Moderate platyspondyly with increased intervertebral disc spaces, underossified pelvic bones and proximal femurs. c Patient 3, age 19 years. Note

kyphoscoliosis, thin ribs, abnormal pelvis with narrow ilia, shallow acetabula, thin ischia and pubic rami, and coxa valga

a b c

Fig. 92.4 a, b. Patient 2, age 4 days. Hypoplasia of the meta- carpals (a) and metatarsals (b), most pronounced in the thumbs and great toes; hypoplasia of middle phalanges of fin-

gers, especially fingers 2 and 5, with clinodactyly; aplasia of middle phalanges of toes; and unossified tarsal bones

a b