Breast carcinoma, and Genu valgum

Neurofibromatosis type I is an autosomal dominant disorder characterized by cafe-au-lait spots, Lisch nodules in the eye, and fibromatous tumors of the skin. Individuals with the disorder have increased susceptibility to the development of benign and malignant tumors. NF1 is sometimes referred to as 'peripheral neurofibromatosis.' The worldwide incidence of NF1 is 1 in 2,500 to 1 in 3,000 individuals (reviews by Shen et al., 1996 and Williams et al., 2009).Type II neurofibromatosis (NF2 ) is a genetically distinct disorder caused by mutation in the gene encoding merlin (NF2 ) on chromosome 22q12. NF2, sometimes known as 'central neurofibromatosis,' is characterized by bilateral acoustic neuroma and meningioma, but few skin lesions or neurofibromas (Rouleau et al., 1993).Some patients with homozygous or compound heterozygous mutations in mismatch repair genes (see, e.g., MLH1; {120436} and MSH2; {609309}) have a phenotype characterized by early onset malignancies and mild features of NF1, especially cafe-au-lait spots; this is known as the mismatch repair cancer syndrome (OMIM ), sometimes referred to as brain tumor-polyposis syndrome-1 or Turcot syndrome. These patients typically do not have germline mutations in the NF1 gene, although a study by Wang et al. (2003) suggested that biallelic mutations in mismatch repair genes may cause somatic mutations in the NF1 gene, perhaps resulting in isolated features resembling NF1.See also Legius syndrome (OMIM ), a genetically distinct disorder with a similar phenotype to NF1.

NEUROFIBROMATOSIS TYPE 1 DUE TO NF1 MUTATION OR INTRAGENIC DELETION Is also known as von recklinghausen disease due to nf1 mutation or intragenic deletion|neurofibromatosis, peripheral type|von recklinghausen disease

• Intellectual disability
• Seizures
• Short stature
• Scoliosis
• Hypertelorism

SOURCES: ORPHANET OMIM MENDELIAN

Carpenter syndrome is a subtype of a family of genetic disorders known as acrocephalopolysyndactyly (ACPS) disorders.

CARPENTER SYNDROME Is also known as acrocephalopolysyndactyly type 2|acps2

• Intellectual disability
• Global developmental delay
• Hypertelorism
• Sensorineural hearing impairment
• Abnormal facial shape

SOURCES: ORPHANET OMIM MENDELIAN

CHST3-related skeletal dysplasia is a very rare bone disorder characterized clinically by short stature of prenatal onset; dislocation of the knees, hips or elbows; club feet; limitation of range of motion of large joints; progressive kyphosis; and occasional scoliosis. In a few patients, minor heart valve dysplasia has also been described. Intellect, vision and hearing are normal.

CHST3-RELATED SKELETAL DYSPLASIA Is also known as chondrodysplasia with multiple dislocations|cdmd|humerospinal dysostosis|spondyloepiphyseal dysplasia with congenital joint dyslocations, chst3 type|sdcd, chst3 type|hsd|spondyloepiphyseal dysplasia, omani type|chondrodysplasia with congenital joint dislo

• Short stature
• Hearing impairment
• Scoliosis
• Hypertelorism
• Abnormal facial shape

SOURCES: OMIM ORPHANET MENDELIAN

Ear-patella-short stature syndrome is an association of malformations including bilateral microtia (severe hypoplasia of ear pinnae), absent patellae, short stature, poor weight gain, and characteristic facial features such as high forehead, micrognathism with full lips and small mouth, and accentuated nasolabial folds (smile wrinkles linking the nostrils to the labial commissure).

EAR-PATELLA-SHORT STATURE SYNDROME Is also known as microtia, absent patellae, micrognathia syndrome|meier-gorlin syndrome|eps|ear, patella, short stature syndrome

• Intellectual disability
• Global developmental delay
• Short stature
• Hearing impairment
• Microcephaly

SOURCES: OMIM ORPHANET MENDELIAN

Frank-ter Haar syndrome (formerly considered as an autosomal recessive form of Melnick-Needles syndrome; see this term) is defined by megalocornea, multiple skeletal anomalies, characteristic facial dysmorphism (wide fontanels, prominent forehead, hypertelorism, prominent eyes, full cheeks and micrognathia) and developmental delay.

FRANK-TER HAAR SYNDROME Is also known as ter haar syndrome|borrone dermatocardioskeletal syndrome|melnick-needles syndrome, autosomal recessive, formerly

• Intellectual disability
• Global developmental delay
• Short stature
• Scoliosis
• Growth delay

SOURCES: OMIM ORPHANET MESH MENDELIAN

Langer-Giedon syndrome, also known as trichorhinophalangeal syndrome type 2, is a very rare, genetic, multiple congenital anomaly disorder characterized by bone abnormalities, distinctive facial features, multiple exostoses, and intellectual disability.

TRICHORHINOPHALANGEAL SYNDROME TYPE 2 Is also known as langer-giedion syndrome|deletion 8q24.1|chromosome 8q24.1 deletion syndrome|lgs|monosomy 8q24.1

• Intellectual disability
• Seizures
• Short stature
• Generalized hypotonia
• Hearing impairment

SOURCES: ORPHANET OMIM MESH MENDELIAN

Intellectual disability-cataracts-calcified pinnae-myopathy syndrome is a rare, genetic intellectual disability syndrome characterized by macrocephaly, hypotonia, dysmorphic facial features (wide forehead, ptosis, downslanting palpebral fissures, enlarged and calcified external ears, large jaw), sparse body hair, tall stature, and intellectual disability. Hearing loss, insulin-resistant diabetes, and progressive distal muscle wasting (leading to joint contractures) have also been reported in adulthood. Rare manifestations include behavioral abnormalities (aggression and restlessness), hypothyroidism, cerebral calcification, ataxia, and peripheral neuropathy.

INTELLECTUAL DISABILITY-CATARACTS-CALCIFIED PINNAE-MYOPATHY SYNDROME Is also known as primrose syndrome|ossified ear cartilages with mental deficiency, muscle wasting, and bony changes

• Intellectual disability
• Seizures
• Global developmental delay
• Short stature
• Generalized hypotonia

SOURCES: ORPHANET OMIM MESH MENDELIAN

Hurler-Scheie syndrome is the intermediate form of mucopolysaccharidosis type 1 (MPS1; see this term) between the two extremes Hurler syndrome and Scheie syndrome (see these terms); it is a rare lysosomal storage disease, characterized by skeletal deformities and a delay in motor development.

HURLER-SCHEIE SYNDROME Is also known as mucopolysaccharidosis type 1h/s|mucopolysaccharidosis type ih/s|mpsih/s|mps1-hs|mps1h/s

• Intellectual disability
• Global developmental delay
• Short stature
• Hearing impairment
• Scoliosis

SOURCES: ORPHANET MENDELIAN

Fanconi anemia complementation group S is an autosomal recessive disorder characterized by developmental delay apparent from infancy, short stature, microcephaly, and coarse dysmorphic features. Laboratory studies show defective DNA repair and increased chromosomal breakage during stress. Some patients may have radial ray anomalies, anemia, and increased risk of cancer; patients often have a family history of cancer in family members who have heterozygous mutations (summary by Freire et al., 2018).For additional general information and a discussion of genetic heterogeneity of Fanconi anemia, see {227650}.

• Intellectual disability
• Global developmental delay
• Short stature
• Hearing impairment
• Microcephaly

SOURCES: OMIM MENDELIAN

Pachydermoperiostosis (PDP) is a form of primary hypertrophic osteoarthropathy (see this term), a rare hereditary disorder, and is characterized by digital clubbing, pachydermia and subperiosteal new bone formation associated with pain, polyarthritis, cutis verticis gyrata, seborrhea and hyperhidrosis. Three forms have been described: a complete form with pachydermia and periostitis, an incomplete form with evidence of bone abnormalities but lacking pachydermia, and a forme frusta with prominent pachydermia and minimal-to-absent skeletal changes.

PACHYDERMOPERIOSTOSIS Is also known as touraine-solente-gole syndrome|pdp

• Scoliosis
• Ptosis
• Anemia
• Hepatomegaly
• Edema

SOURCES: ORPHANET MENDELIAN