Ventricular septal defect, and Pheochromocytoma

Medium match RUBINSTEIN-TAYBI SYNDROME 1; RSTS1

Rubinstein-Taybi syndrome is a multiple congenital anomaly syndrome characterized by mental retardation, postnatal growth deficiency, microcephaly, broad thumbs and halluces, and dysmorphic facial features. The facial appearance is striking, with highly arched eyebrows, long eyelashes, downslanting palpebral fissures, broad nasal bridge, beaked nose with the nasal septum, highly arched palate, mild micrognathia, and characteristic grimacing or abnormal smile. Affected individuals also have an increased risk of tumor formation (Rubinstein and Taybi, 1963; review by Hennekam, 2006).Floating-Harbor syndrome (OMIM ), which shows phenotypic overlap with Rubinstein-Taybi syndrome, is caused by mutation in the SRCAP gene (OMIM ), a coactivator for CREBBP. Genetic Heterogeneity of Rubinstein-Taybi SyndromeRubinstein-Taybi syndrome-1 (RSTS1) constitutes about 50 to 70% of patients with the disorder. Rubinstein-Taybi syndrome-2 (RSTS2 ) comprises about 3% of patients and is primarily due to de novo heterozygous mutation in the EP300 gene (OMIM ) on chromosome 22q13 (Bartsch et al., 2010).See also chromosome 16p13.3 deletion syndrome (OMIM ), a severe form of Rubinstein-Taybi syndrome resulting from a contiguous gene deletion involving the CREBBP gene as well as other neighboring genes.

RUBINSTEIN-TAYBI SYNDROME 1; RSTS1 Is also known as broad thumbs and great toes, characteristic facies, and mental retardation|rubinstein syndrome|rsts|broad thumb-hallux syndrome

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

SOURCES: OMIM MENDELIAN

Low match NEUROFIBROMATOSIS TYPE 1 DUE TO NF1 MUTATION OR INTRAGENIC DELETION

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

Low match COMBINED OXIDATIVE PHOSPHORYLATION DEFECT TYPE 15

Combined oxidative phosphorylation defect type 15 is a rare mitochondrial disease due to a defect in mitochondrial protein synthesis characterized by onset in infancy or early childhood of muscular hypotonia, gait ataxia, mild bilateral pyramidal tract signs, developmental delay (affecting mostly speech and coordination) and subsequent intellectual disability. Short stature, obesity, microcephaly, strabismus, nystagmus, reduced visual acuity, lactic acidosis, and a brain neuropathology consistent with Leigh syndrome are also reported.

COMBINED OXIDATIVE PHOSPHORYLATION DEFECT TYPE 15 Is also known as coxpd15

• Seizures
• Global developmental delay
• Short stature
• Generalized hypotonia
• Microcephaly

SOURCES: ORPHANET OMIM MENDELIAN

Low match LATERAL MENINGOCELE SYNDROME

Lateral meningocele syndrome is a rare disorder characterized by distinctive facial features, hyperextensibility, hypotonia, and characteristic lateral meningoceles, which can result in neurologic complications such as bladder dysfunction and neuropathy. Dysmorphic features include dolichocephaly, hypertelorism, ptosis, microretrognathia, high-arched palate, long, flat philtrum, and low-set ears. Multiple additional variable features may also be observed, including cryptorchidism, vertebral anomalies, and connective tissue abnormalities. Early motor development is delayed, but cognition is usually normal (summary by Gripp et al., 2015).

LATERAL MENINGOCELE SYNDROME Is also known as lehman syndrome|lms

• Global developmental delay
• Short stature
• Generalized hypotonia
• Hearing impairment
• Scoliosis

SOURCES: ORPHANET OMIM MENDELIAN

Low match PARAGANGLIOMAS 5; PGL5

• Neoplasm
• Hypertension
• Hyperhidrosis
• Vertigo
• Tachycardia

SOURCES: OMIM MENDELIAN

Low match PARAGANGLIOMAS 1; PGL1

Paragangliomas, also referred to as 'glomus body tumors,' are tumors derived from paraganglia located throughout the body. Nonchromaffin types primarily serve as chemoreceptors (hence, the tumor name 'chemodectomas') and are located in the head and neck region (i.e., carotid body, jugular, vagal, and tympanic regions), whereas chromaffin types have endocrine activity, conventionally referred to as 'pheochromocytomas,' and are usually located below the head and neck (i.e., adrenal medulla and pre- and paravertebral thoracoabdominal regions). PGL can manifest as nonchromaffin head and neck tumors only, adrenal and/or extraadrenal pheochromocytomas only, or a combination of the 2 types of tumors (Baysal, 2002; Neumann et al., 2004).The triad of gastric leiomyosarcoma, pulmonary chondroma, and extraadrenal paraganglioma constitutes a syndrome that occurs mainly in young women and is known as the Carney triad (OMIM ). This triad is not to be confused with the other Carney syndrome of myxoma, spotty pigmentation, and endocrinopathy (OMIM ).Baysal (2008) provided a review of the molecular pathogenesis of hereditary paraganglioma. Genetic Heterogeneity of ParagangliomasSee also PGL4 (OMIM ), caused by mutation in the SDHB gene (OMIM ) on chromosome 1p36; PGL3 (OMIM ), caused by mutation in the SDHC gene (OMIM ) on chromosome 1q21; PGL2 (OMIM ), caused by mutation in the SDHAF2 gene (OMIM ) on chromosome 11q13; and PGL5 (OMIM ), caused by mutation in the SDHA gene (OMIM ) on chromosome 5p15.

PARAGANGLIOMAS 1; PGL1 Is also known as paraganglioma, carotid body|glomus tumors, familial, 1|cbt1|glomus jugulare tumors|paragangliomas, familial, 1|chemodectomas|paragangliomas, familial nonchromaffin, 1|carotid body tumors|pgl|paragangliomata

• Neoplasm
• Pain
• Hypertension
• Hyperhidrosis
• Dyspnea

SOURCES: OMIM MENDELIAN

Low match FANCONI ANEMIA, COMPLEMENTATION GROUP N; FANCN

Fanconi anemia (FA) is a clinically and genetically heterogeneous disorder that causes genomic instability. Characteristic clinical features include developmental abnormalities in major organ systems, early-onset bone marrow failure, and a high predisposition to cancer. The cellular hallmark of FA is hypersensitivity to DNA crosslinking agents and high frequency of chromosomal aberrations pointing to a defect in DNA repair (summary by Deakyne and Mazin, 2011).For additional general information and a discussion of genetic heterogeneity of Fanconi anemia, see {227650}.

• Microcephaly
• Growth delay
• Hypertelorism
• Neoplasm
• Failure to thrive

SOURCES: MESH OMIM MENDELIAN

Low match ISOLATED HEMIHYPERPLASIA

Isolated hemihyperplasia is a rare overgrowth syndrome characterized by an asymmetric regional body overgrowth, involving at least one limb, and associated with an increased risk of developing embryonal tumors, principally nephroblastoma (see this term) and hepoblastoma.

ISOLATED HEMIHYPERPLASIA Is also known as hemicorporal hypertrophy|hemi 3 syndrome|hemihypertrophy, isolated|hemihyperplasia|isolated hemihypertrophy|hhp

• Seizures
• Scoliosis
• Neoplasm
• Cryptorchidism
• Hydrocephalus

SOURCES: OMIM ORPHANET MESH MENDELIAN

Low match OSTEOPOROSIS-PSEUDOGLIOMA SYNDROME

Osteoporosis pseudoglioma syndrome is a very rare autosomal recessive disorder characterized by congenital or infancy-onset blindness and severe juvenile-onset osteoporosis and spontaneous fractures.

OSTEOPOROSIS-PSEUDOGLIOMA SYNDROME Is also known as oppg|osteogenesis imperfecta, ocular form|ocular form of osteogenesis imperfecta|ops

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

SOURCES: OMIM MESH ORPHANET MENDELIAN

Low match CARNEY COMPLEX

Carney complex (CNC) is characterized by spotty skin pigmentation, endocrine overactivity and myxomas.

CARNEY COMPLEX Is also known as myxoma-spotty pigmentation-endocrine overactivity syndrome|carney syndrome|carney myxoma-endocrine complex, type 2

• Neoplasm
• Congestive heart failure
• Stroke
• Hirsutism
• Sudden cardiac death

SOURCES: ORPHANET OMIM MENDELIAN