Cri du chat syndrome and Williams syndrome | USMLE step 1| Lecture 17

5p deletion syndrome (cri-du-chat syndrome) — Cri-du-chat (cat cry) is a deletion syndrome, with an incidence of approximately 1 in 45,000 liveborn infants. Approximately 85 percent of cases result from a de novo partial deletion of the short arm of chromosome 5 (the deleted chromosome is of paternal origin in 80 percent). The remaining cases derive from a parental translocation involving 5p. The critical region for the high-pitched, cat-like crying is 5p15.3, while the remaining clinical features of this syndrome are mapped to a smaller region within 5p15.2.

Patients with cri-du-chat or cat cry syndrome have a mew-like cry early on in life that quickly resolves (apparently related to vocal cord abnormalities) and low birth weight, failure to thrive, hypotonia, psychomotor delay, intellectual disability, microcephaly, hypertelorism, round face, downslanting palpebral fissures, broad nasal bridge, and low-set and/or malformed ears. Genotype-phenotype correlation in one series of 62 patients with terminal deletions showed progressive severity of clinical features (eg, degree of microcephaly) and psychomotor retardation according to the size of the deletion. With advancing age, the clinical manifestations become less striking, making diagnosis more difficult. Most children, but not all, have low weight for age and, to a lesser extent, shortened height for age.

Williams syndrome also known as Williams-Beuren syndrome, is a multisystem, contiguous gene deletion syndrome caused by hemizygous deletion of 1.5 to 1.8 Mb on chromosome 7q11.23.
EPIDEMIOLOGY: First described clinically in 1961, the use of genetic testing to confirm the diagnosis has demonstrated that WS is one of the more common genetic disorders with an estimated incidence of 1:7500 live births.
GENETICS: WS is caused by a 1.5 to 1.8 Mb recurrent microdeletion of 7q11.23. While the disease is transmitted in an autosomal dominant fashion, almost all cases are the result of de novo mutations. The deletion encompasses approximately 28 genes, including the elastin gene, ELN. Although ELN and other genes of interest are located in the area of the mutation, no single gene has been identified that results in the full WS phenotype. Hemizygosity for ELN is responsible for the vascular and cardiac valvar abnormalities and some of the facial features of WS as elastin fibers are a key component of the extracellular matrix and confer elasticity to tissues and organs. Haploinsufficiency of adjacent genes, such as LIMK1, probably accounts for the other manifestations of this disorder, including the impaired visuospatial constructive cognition and developmental delay.
Facial dysmorphic features — Young individuals with WS have distinctive "elfin" facies. Facial features include:

●Broad forehead

●Bitemporal narrowness

●Medial eyebrow flare

●Strabismus

●Flat nasal bridge

●Malar flattening

●Shortnose with a long philtrum, full lips, and a wide mouth

CVS: supraclavicular aortic stenosis, renal artery stenosis.
Other: Hypercalcemia, well developed verbal skills, extreme friendliness with strangers