Differentials
Turner syndrome
SIGNS / SYMPTOMS
Hypergonadotropic hypogonadism and abnormal karyotype.
INVESTIGATIONS
Karyotype test will identify abnormal chromosomes.
LEOPARD syndrome
Cardio-facio-cutaneous syndrome
SIGNS / SYMPTOMS
Severe cognitive impairment; coarser facial appearance than NS, which increases with age; a high frequency of structural CNS abnormalities (especially hydrocephaly and ventriculomegaly); a higher likelihood of seizures and optic nerve dysplasia than NS; and severe and persistent gastrointestinal dysmotility.[64]
INVESTIGATIONS
Molecular genetic testing will identify mutations in BRAF, MAP2K1, and MAP2K2.
Although KRAS mutations may cause both cardio-facio-cutaneous syndrome and NS, the mutations concerned are different.[64]
Costello syndrome
SIGNS / SYMPTOMS
Moderate cognitive impairment, coarser facial features than NS, chaotic atrial rhythms, deep palmar and plantar creases; development of perinasal, perioral, and perianal warts; and a 10% to 15% predisposition to tumors (e.g., embryonal rhabdomyosarcoma, neuroblastoma, and transitional cell bladder cancer).[65]
INVESTIGATIONS
Molecular genetic testing will identify mutations in HRAS, another gene in the Ras/MAPK pathway.[65]
Neurofibromatosis type 1
SIGNS / SYMPTOMS
Familial cancer syndrome; hallmark features include hyperpigmented skin lesions and benign neurofibromas; learning disabilities are common.[1]
INVESTIGATIONS
Molecular genetic testing will identify mutations in neurofibromin 1 (NF1), another gene in the Ras/MAPK pathway.
Williams syndrome
SIGNS / SYMPTOMS
Supravalvular aortic stenosis; hypercalcemia; characteristic appearance, with periorbital fullness, long philtrum, and full lips; unique cognitive profile and typical "cocktail party" personality.
INVESTIGATIONS
Caused by a deletion of chromosome 7q11.23, which is best identified by a fluorescence in situ hybridization technique.
Aarskog syndrome
SIGNS / SYMPTOMS
Short fingers with hyperextensible joints and excess webbing between the digits; facial appearance with tall, prominent forehead and upturned corners of the mouth; "shawl" scrotum; lack of significant intellectual handicap; X-linked pattern of inheritance.
INVESTIGATIONS
Molecular genetic testing will identify mutations in FGD1 on the X chromosome.
Noonan-like syndrome
SIGNS / SYMPTOMS
Easily pluckable, sparse, thin, slow-growing hair; darkly pigmented skin; increased likelihood of mitral valve dysplasia or septal defects; growth hormone deficiency; and distinctive behavior.
INVESTIGATIONS
A recurrent missense mutation in SHOC2 is found in this cohort with NS-like features. Rarely, a classical Noonan syndrome phenotype is found.
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