Delayed speech and language development, and Subcutaneous nodule

Medium match LIPOID PROTEINOSIS OF URBACH AND WIETHE

Lipoid proteinosis of Urbach and Wiethe is a rare autosomal recessive disorder typified by generalized thickening of skin, mucosae, and certain viscera. Classic features include beaded eyelid papules and laryngeal infiltration leading to hoarseness. The disorder is clinically heterogeneous, with affected individuals displaying differing degrees of skin scarring and infiltration, variable signs of hoarseness and respiratory distress, and in some cases neurologic abnormalities such as temporal lobe epilepsy. Histologically, there is widespread deposition of hyaline (glycoprotein) material and disruption/reduplication of basement membrane (summary by Hamada et al., 2002 and Hamada et al., 2003).

LIPOID PROTEINOSIS OF URBACH AND WIETHE Is also known as lipoid proteinosis, urbach-wiethe disease, hyalinosis cutis et mucosae;hyalinosis cutis et mucosae; urbach-wiethe disease

• Autosomal recessive inheritance
• Intellectual disability
• Seizures
• Pica
• High palate

SOURCES: SCTID MESH GARD DOID OMIM NCIT UMLS ORPHANET MONDO

Medium match ENCEPHALOCRANIOCUTANEOUS LIPOMATOSIS; ECCL

Encephalocraniocutaneous lipomatosis (ECCL) is a neurocutaneous disorder characterized by ocular anomalies, skin lesions, and central nervous system (CNS) anomalies (Moog et al., 2007).The malformations in ECCL are patchy and asymmetric. The most characteristic skin anomaly is nevus psiloliparus, a well-demarcated, alopecic fatty tissue nevus on the scalp, seen in 80% of affected individuals. Other dermatologic features include frontotemporal or zygomatic subcutaneous fatty lipomas, non-scarring alopecia, focal dermal hypoplasia or aplasia of the scalp, periocular skin tags, and pigmentary abnormalities following the lines of Blaschko. Choristomas of the eye (epibulbar dermoids or lipodermoids) are also present in 80% of patients, and can be unilateral or bilateral. Characteristic CNS features in ECCL include intracranial and intraspinal lipomas, seen in 61% of patients, and less often cerebral asymmetry, arachnoid cysts, enlarged ventricles, and leptomeningeal angiomatosis. A predisposition to low-grade gliomas has also been observed. Seizures and intellectual disability are common, but one-third of affected individuals have normal intellect. Skeletal manifestations include bone cysts and jaw tumors, such as odontomas, osteomas, and ossifying fibromas (summary by Bennett et al., 2016).

ENCEPHALOCRANIOCUTANEOUS LIPOMATOSIS; ECCL Is also known as ;haberland syndrome

• Intellectual disability
• Seizures
• Global developmental delay
• Pica
• Failure to thrive

SOURCES: ORPHANET SCTID MESH GARD OMIM UMLS MONDO NCIT

Medium match BANNAYAN-RILEY-RUVALCABA SYNDROME; BRRS

Bannayan-Riley-Ruvalcaba syndrome (BRRS) is a rare congenital disorder characterized by hamartomatous intestinal polyposis, lipomas, macrocephaly and genital lentiginosis.

BANNAYAN-RILEY-RUVALCABA SYNDROME; BRRS Is also known as bannayan-zonana syndrome;bzs, riley-smith syndrome, ruvalcaba-myhre-smith syndrome;rmss, macrocephaly, pseudopapilledema, and multiple hemangiomata, macrocephaly, multiple lipomas, and hemangiomata;brrs; myhre-riley-smith syndrome

• Autosomal dominant inheritance
• Intellectual disability
• Seizures
• Global developmental delay
• Short stature

SOURCES: DOID GARD NCIT MONDO SCTID ORPHANET OMIM ICD10

Low match TUBEROUS SCLEROSIS 2; TSC2

Tuberous sclerosis complex (TSC) is an autosomal dominant multisystem disorder characterized by hamartomas in multiple organ systems, including the brain, skin, heart, kidneys, and lung. These changes can result in epilepsy, learning difficulties, behavioral problems, and renal failure, among other complications (reviews by Crino et al., 2006 and Curatolo et al., 2008).For a general phenotypic description and a discussion of genetic heterogeneity of tuberous sclerosis, see tuberous sclerosis-1 (OMIM ), caused by mutation in the TSC1 gene (OMIM ) on chromosome 9q34.Approximately 10 to 30% of cases of tuberous sclerosis are due to mutations in the TSC1 gene: the frequency of cases due to mutations in the TSC2 gene is consistently higher. TSC2 mutations are associated with more severe disease (Crino et al., 2006) (see GENOTYPE/PHENOTYPE CORRELATIONS section).

• Autosomal dominant inheritance
• Intellectual disability
• Seizures
• Global developmental delay
• Motor delay

SOURCES: NCIT MONDO OMIM GARD UMLS

Low match CATARACTS, GROWTH HORMONE DEFICIENCY, SENSORY NEUROPATHY, SENSORINEURAL HEARING LOSS, AND SKELETAL DYSPLASIA; CAGSSS

CATARACTS, GROWTH HORMONE DEFICIENCY, SENSORY NEUROPATHY, SENSORINEURAL HEARING LOSS, AND SKELETAL DYSPLASIA; CAGSSS Is also known as ;cagsss

• Autosomal recessive inheritance
• Short stature
• Hearing impairment
• Scoliosis
• Nystagmus

SOURCES: OMIM ORPHANET UMLS MONDO

Low match PAGET DISEASE OF BONE 5, JUVENILE-ONSET; PDB5

Paget disease of bone-5 is an autosomal recessive, juvenile-onset form of Paget disease, a disorder of the skeleton resulting from abnormal bone resorption and formation. Clinical manifestations include short stature, progressive long bone deformities, fractures, vertebral collapse, skull enlargement, and hyperostosis with progressive deafness. There is phenotypic variability, with some patients presenting in infancy, while others present later in childhood (summary by Naot et al., 2014).For discussion of genetic heterogeneity of Paget disease of bone, see {167250}.

PAGET DISEASE OF BONE 5, JUVENILE-ONSET; PDB5 Is also known as juvenile paget disease;jpd, hyperostosis corticalis deformans juvenilis, hyperphosphatasia, familial idiopathic, hyperphosphatasemia, chronic congenital idiopathic, osteoectasia, familial;familial osteoectasia; hereditary hyperphosphatasia; hyperostosis corticalis deformans juvenilis; jpg; juvenile paget's disease

• Autosomal recessive inheritance
• Global developmental delay
• Short stature
• Hearing impairment
• Sensorineural hearing impairment

SOURCES: ORPHANET OMIM SCTID NCIT MONDO MESH UMLS GARD

Low match MICROCEPHALY-LYMPHEDEMA-CHORIORETINOPATHY SYNDROME

Microcephaly with or without chorioretinopathy, lymphedema or intellectual disability (MCLID) is a rare autosomal dominant condition characterized by variable expression of microcephaly, ocular disorders including chorioretinopathy, congenital lymphedema of the lower limbs, and mild to moderate intellectual disability.

MICROCEPHALY-LYMPHEDEMA-CHORIORETINOPATHY SYNDROME Is also known as mlcrd

• Intellectual disability
• Seizures
• Global developmental delay
• Microcephaly
• Muscular hypotonia

SOURCES: ORPHANET UMLS

Low match FARBER LIPOGRANULOMATOSIS; FRBRL

Farber lipogranulomatosis is an autosomal recessive lysosomal storage disorder characterized by early-onset subcutaneous nodules, painful and progressively deformed joints, and hoarseness by laryngeal involvement. Based on the age of onset, the severity of symptoms, and the difference in organs affected, 6 clinical subtypes due to deficiency of acid ceramidase have been distinguished. The most severe form is subtype 4, a rare neonatal form of the disease with death occurring before 1 year of age (summary by Alves et al., 2013).

FARBER LIPOGRANULOMATOSIS; FRBRL Is also known as farber disease, ceramidase deficiency, acid ceramidase deficiency, ac deficiency, n-laurylsphingosine deacylase deficiency;acid ceramidase deficiency; farber lipogranulomatosis

• Autosomal recessive inheritance
• Intellectual disability
• Global developmental delay
• Short stature
• Pica

SOURCES: ORPHANET SCTID DOID UMLS MESH GARD MONDO OMIM NCIT

Low match MULTIPLE ENDOCRINE NEOPLASIA, TYPE IIB; MEN2B

Multiple endocrine neoplasia type IIB (MEN2B) is an autosomal dominant hamartoneoplastic syndrome characterized by aggressive medullary thyroid carcinoma (MTC), pheochromocytoma, mucosal neuromas, and thickened corneal nerves. Most affected individuals have characteristic physical features, including full lips, thickened eyelids, high-arched palate, and marfanoid habitus. Other more variable features include skeletal anomalies and gastrointestinal problems (review by Morrison and Nevin, 1996).For a discussion of genetic heterogeneity of multiple endocrine neoplasia (MEN), see MEN1 (OMIM ).

MULTIPLE ENDOCRINE NEOPLASIA, TYPE IIB; MEN2B Is also known as men iib, neuromata, mucosal, with endocrine tumors, wagenmann-froboese syndrome, multiple endocrine neoplasia, type iii, formerly;men3, formerly;men2b; multiple endocrine neoplasia type 3; wagenmann-froboese syndrome

• Autosomal dominant inheritance
• Seizures
• Global developmental delay
• Generalized hypotonia
• Scoliosis

SOURCES: ORPHANET SCTID OMIM UMLS ICD10

Low match BEARE-STEVENSON CUTIS GYRATA SYNDROME; BSTVS

Cutis gyrata-acanthosis nigricans-craniosynostosis syndrome, also known as Beare-Stevenson syndrome (BSS), is a severe form of syndromic craniosynostosis, characterized by a variable degree of craniosynostosis, with cloverleaf skull reported in over 50% of cases, cutis gyrata, corduroy-like linear striations in the skin, acanthosis nigricans, skin tags, and choanal stenosis or atresia). Additional features include facial features similar to Crouzon disease, ear defects (conductive hearing loss, posteriorly angulated ears, stenotic auditory canals, preauricular furrows, and narrow ear canals), hirsutism, a prominent umbilical stump, and genitorurinary anomalies (anteriorly placed anus, hypoplasic labia, hypospadias). BSS is associated with a poor outcome as patients present an elevated risk for sudden death in their first year of life. Significant developmental delay and intellectual disability are observed in most patients who survive infancy.

BEARE-STEVENSON CUTIS GYRATA SYNDROME; BSTVS Is also known as beare-stevenson syndrome, cutis gyrata syndrome of beare and stevenson;beare-stevenson cutis gyrata syndrome

• Autosomal dominant inheritance
• Global developmental delay
• Hypertelorism
• Strabismus
• Ptosis

SOURCES: OMIM ORPHANET NCIT DOID MESH SCTID GARD UMLS MONDO