Chromosomal disorders are diseases associated with abnormal karyotyping. Karyotyping should be performed with chromosomes in metaphase in order to detect subtle abnormalities. Hypotonia occurs with a significant number of chromosomal abnormalities. Down syndrome is the most common chromosomal abnormality associated with hypotonia during the neonatal period.

Down Syndrome
The diagnosis of Down syndrome is usually obvious. Neonates with Down syndrome have brachycephaly, flat occiput, upward-slanting palpebral fissures, epicanthal folds, Brushfield spots, fissures on the tongue, low-set ears with prominent antihelix, angular overlapping helix, brachydactyly, clinodactyly, simian creases, small middle phalanx of the second and fifth fingers, and a wide space between the first and second toes (Figure 111.1). Neonates with Down syndrome have hypotonia with decreased dynamic tone. Lax ligaments contribute to hypotonia. Seizures occur in less than 10% of patients with Down syndrome. Endocardial cushion defects may be present. Duodenal atresia, anal atresia, and megacolon are less frequent. Upper cervical vertebral abnormality may lead to atlantoaxial dislocation. Atlantoaxial dislocation may produce apnea and quadriparesis. Down syndrome is due to trisomy of all, or a large part, of chromosome 21. Trisomy 21 has a recurrence of 1%. D/G and G/G translocations are rare but they should be considered because they have significant genetic implications. Parents of infants with a translocation may be carriers of a balance translocation, therefore, they are more likely to have other children with Down syndrome than parents who are not carriers of a balance translocation. The diagnosis is established by karyotyping. More about... 275

A	B	C

Figure 111.1.— Characteristic findings in neonates with Down syndrome. [A] Upward-slanting palpebral features, [B] simian crease, [C] wide space between the first and second toes.

Genetic disorders are a group of syndromes with normal karyotype but with abnormal genes detected using DNA testing or a family history that suggests a genetic origin. Prader-Willi and Lowe syndromes are frequent causes of neonatal hypotonia. They course with hypotonia and decreased dynamic tone.

Prader-Willi Syndrome
Neonates with Prader-Willi syndrome usually have bitemporal narrowing, prominent forehead, almond-shaped eyes, strabismus, dysmorphic ears with narrow external canal, triangular mouth, poor sucking and swallowing reflexes at birth, small hands and feet, small penis, and cryptorchidism. Most patients have a paternally transmitted deletion of chromosome 15 (15q11-12). Prader-Willi syndrome should be suspected in all neonates with central hypotonia. The diagnosis is established by DNA testing. Fluorescent in situ hybridization for Prader-Willi syndrome is negative in about one-third of neonates with Prader-Willi syndrome.

A	B	C

Figure 111.2— Prader-Willi syndrome. [A] Bitemporal narrowing, prominent forehead, almond-shaped eyes, triangular mouth, and poor sucking and swallowing reflexes at birth; [B] small penis; and [C] cryptorchidism.

Lowe Syndrome
Lowe syndrome or oculocerebrorenal syndrome is characterized by cataracts, megalocornea, buphthalmos, glaucoma, prominent forehead, protruding tongue, thin sparse hair, proteinuria, metabolic acidosis, amino aciduria, and defective acidification of urine. Cryptorchidism is common. Lowe syndrome is transmitted by X-linked, recessive inheritance. Mothers of infants with Lowe syndrome may have minor lenticular opacities. Diagnosis is established by the presence of hypotonia, ocular abnormality, and laboratory evidence of renal involvement.