Delayed speech and language development, and Hepatic fibrosis

Medium match NEUROLOGIC, ENDOCRINE, AND PANCREATIC DISEASE, MULTISYSTEM, INFANTILE-ONSET; IMNEPD

NEUROLOGIC, ENDOCRINE, AND PANCREATIC DISEASE, MULTISYSTEM, INFANTILE-ONSET; IMNEPD Is also known as ;imnepd

• Autosomal recessive inheritance
• Intellectual disability
• Global developmental delay
• Short stature
• Generalized hypotonia

SOURCES: OMIM UMLS ORPHANET MONDO

Medium match CONGENITAL DISORDER OF GLYCOSYLATION, TYPE Im; CDG1M

gene led to a 96 to 98% reduction in DK activity.

CONGENITAL DISORDER OF GLYCOSYLATION, TYPE Im; CDG1M Is also known as cdg im;cdgim, dolichol kinase deficiency, dk1 deficiency;cdg syndrome type im; cdg-im; cdg1m; carbohydrate deficient glycoprotein syndrome type im; congenital disorder of glycosylation type 1m; congenital disorder of glycosylation type im; dolichol kinase deficiency; hypotonia and ichthyosis due to dolichol phosphate deficiency

• Autosomal recessive inheritance
• Seizures
• Global developmental delay
• Short stature
• Generalized hypotonia

SOURCES: ORPHANET UMLS MESH OMIM MONDO SCTID GARD

Medium match PEROXISOME BIOGENESIS DISORDER 1B; PBD1B

Peroxisome biogenesis disorder-1B (PBD1B) is characterized by the overlapping phenotypes of neonatal adrenoleukodystrophy (NALD) and infantile Refsum disease (IRD), which represent the milder manifestations of the Zellweger syndrome spectrum (ZSS) of peroxisome biogenesis disorders (PBDs). Initial presentation and natural history varies, with many children presenting as newborns, whereas others do not come to attention until later. Most affected children have hypotonia, but unlike Zellweger syndrome (see PBD1A, {214100}) there is a degree of psychomotor development, and some patients achieve head control, sit unsupported, and may even walk independently. Many can communicate, and although language is rare, there have been children who have near normal language for age. Craniofacial anomalies are similar to but less pronounced than in Zellweger syndrome. In some individuals a leukodystrophy develops, with degeneration of myelin, loss of previously acquired skills, and development of spasticity; this may stabilize, or progress and be fatal. In PBD1B, the most common manifestations that are less apparent in ZS are sensorineural hearing loss and retinitis pigmentosa (summary by Steinberg et al., 2006). While Zellweger syndrome usually results in death in the first year of life, children with the NALD presentation may reach their teens, and those with the IRD presentation may reach adulthood (summary by Waterham and Ebberink, 2012).Individuals with mutations in the PEX1 gene have cells of complementation group 1 (CG1, equivalent to CGE). For information on the history of PBD complementation groups, see {214100}. Genetic Heterogeneity of Peroxisome Biogenesis Disorder NALD/IRDThe phenotypic spectrum of NALD/IRD peroxisome biogenesis disorders can be caused by mutation in members of the peroxin (PEX) gene family. The PEX genes encode proteins essential for the assembly of functional peroxisomes (summary by Distel et al., 1996). PBD1B is caused by mutation in the PEX1 gene on chromosome 7q21; PBD2B (OMIM ) is caused by mutation in the PEX5 gene (OMIM ) on chromosome 12p13.3; PBD3B (OMIM ) is caused by mutation in the PEX12 gene (OMIM ) on chromosome 17; PBD4B (OMIM ) is caused by mutation in the PEX6 gene (OMIM ) on chromosome 6p21.1; PBD5B (OMIM ) is caused by mutation in the PEX2 gene (OMIM ) on chromosome 8q21.1; PBD6B (OMIM ) is caused by mutation in the PEX10 gene (OMIM ) on chromosome 1p36.32; PBD7B (OMIM )is caused by mutation in the PEX26 gene (OMIM ) on chromosome 22q11.21; PBD8B (OMIM ) is caused by mutation in the PEX16 gene (OMIM ) on chromosome 11p11; PDB10B (OMIM ) is caused by mutation in the PEX3 gene (OMIM ) on chromosome 6q24; and PBD11B (OMIM ) is caused by mutation in the PEX13 gene (OMIM ) on chromosome 2p15.See PBD1A (OMIM ) for a phenotypic description and a discussion of genetic heterogeneity of Zellweger syndrome, which is also caused by mutation in peroxin genes. The rhizomelic chondrodysplasia subtype of PBD (RCDP1, PBD9; {215100}), and a mild PBD without rhizomelia (PBD9B ), are caused by mutation in the PEX7 gene (OMIM ) on chromosome 6q23.

PEROXISOME BIOGENESIS DISORDER 1B; PBD1B Is also known as peroxisome biogenesis disorder (neonatal adrenoleukodystrophy/infantile refsum disease), peroxisome biogenesis disorder (nald/ird), adrenoleukodystrophy, autosomal neonatal, refsum disease, infantile, infantile phytanic acid storage disease;ird

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

SOURCES: ORPHANET OMIM

Medium match BARDET-BIEDL SYNDROME 1; BBS1

Bardet-Biedl syndrome is an autosomal recessive and genetically heterogeneous ciliopathy characterized by retinitis pigmentosa, obesity, kidney dysfunction, polydactyly, behavioral dysfunction, and hypogonadism (summary by Beales et al., 1999). Eight proteins implicated in the disorder assemble to form the BBSome, a stable complex involved in signaling receptor trafficking to and from cilia (summary by Scheidecker et al., 2014). Genetic Heterogeneity of Bardet-Biedl SyndromeBBS1 is caused by mutation in a gene on chromosome 11q13 (OMIM ); BBS2 (OMIM ), by mutation in a gene on 16q13 (OMIM ); BBS3 (OMIM ), by mutation in the ARL6 gene on 3q11 (OMIM ); BBS4 (OMIM ), by mutation in a gene on 15q22 (OMIM ); BBS5 (OMIM ), by mutation in a gene on 2q31 (OMIM ); BBS6 (OMIM ), by the MKKS gene on 20p12 (OMIM ), mutations in which also cause McKusick-Kaufman syndrome (OMIM ); BBS7 (OMIM ), by mutation in a gene on 4q27 (OMIM ); BBS8 (OMIM ), by mutation in the TTC8 gene on 14q32 (OMIM ); BBS9 (OMIM ), by mutation in a gene on 7p14 (OMIM ); BBS10 (OMIM ), by mutation in a gene on 12q (OMIM ); BBS11 (OMIM ), by mutation in the TRIM32 gene on 9q33 (OMIM ); BBS12 (OMIM ), by mutation in a gene on 4q27 (OMIM ); BBS13 (OMIM ), by mutation in the MKS1 gene (OMIM ) on 17q23, mutations in which also cause Meckel syndrome-1 (OMIM ); BBS14 (OMIM ), by mutation in the CEP290 gene (OMIM ) on 12q21, mutations in which also cause Meckel syndrome-4 (OMIM ) and several other disorders; BBS15 (OMIM ), by mutation in the C2ORF86 gene (OMIM ), which encodes a homolog of the Drosophila planar cell polarity gene 'fritz,' on 2p15; BBS16 (OMIM ), by mutation in the SDCCAG8 gene (OMIM ) on 1q43, mutations in which also cause Senior-Loken syndrome-7 (OMIM ); BBS17 (OMIM ), by mutation in the LZTFL1 gene (OMIM ) on 3p21; BBS18 (OMIM ), by mutation in the BBIP1 gene (OMIM ) on 10q25; BBS19 (OMIM ), by mutation in the IFT27 gene (OMIM ) on 22q12; BBS20 (OMIM ), by mutation in the IFT74 gene (OMIM ) on 9p21; and BBS21 (OMIM ), by mutation in the C8ORF37 gene (OMIM ).The CCDC28B gene (OMIM ) modifies the expression of BBS phenotypes in patients who have mutations in other genes. Mutations in MKS1, MKS3 (TMEM67 ), and C2ORF86 also modify the expression of BBS phenotypes in patients who have mutations in other genes.Although BBS had originally been thought to be a recessive disorder, Katsanis et al. (2001) demonstrated that clinical manifestation of some forms of Bardet-Biedl syndrome requires recessive mutations in 1 of the 6 loci plus an additional mutation in a second locus. While Katsanis et al. (2001) called this 'triallelic inheritance,' Burghes et al. (2001) suggested the term 'recessive inheritance with a modifier of penetrance.' Mykytyn et al. (2002) found no evidence of involvement of the common BBS1 mutation in triallelic inheritance. However, Fan et al. (2004) found heterozygosity in a mutation of the BBS3 gene ({608845.0002}) as an apparent modifier of the expression of homozygosity of the met390-to-arg mutation in the BBS1 gene ({209901.0001}).Allelic disorders include nonsyndromic forms of retinitis pigmentosa: RP51 (OMIM ), caused by TTC8 mutation, and RP55 (OMIM ), caused by ARL6 mutation.

• Autosomal recessive inheritance
• Intellectual disability
• Global developmental delay
• Pica
• Hearing impairment

SOURCES: OMIM UMLS DOID MESH MONDO GARD EFO

Medium match JOUBERT SYNDROME 1; JBTS1

Joubert syndrome is a clinically and genetically heterogeneous group of disorders characterized by hypoplasia of the cerebellar vermis with the characteristic neuroradiologic 'molar tooth sign,' and accompanying neurologic symptoms, including dysregulation of breathing pattern and developmental delay. Other variable features include retinal dystrophy and renal anomalies (Saraiva and Baraitser, 1992; Valente et al., 2005). Genetic Heterogeneity of Joubert SyndromeSee also JBTS2 (OMIM ), caused by mutation in the TMEM216 gene (OMIM ) on chromosome 11q13; JBTS3 (OMIM ), caused by mutation in the AHI1 gene (OMIM ) on chromosome 6q23; JBTS4 (OMIM ), caused by mutation in the NPHP1 gene (OMIM ) on chromosome 2q13; JBTS5 (OMIM ), caused by mutation in the CEP290 gene, also called NPHP6 (OMIM ), on chromosome 12q21.32; JBTS6 (OMIM ), caused by mutation in the TMEM67 gene (OMIM ) on chromosome 8q21; JBTS7 (OMIM ), caused by mutation in the RPGRIP1L gene (OMIM ) on chromosome 16q12.2; JBTS8 (OMIM ), caused by mutation in the ARL13B (OMIM ) on chromosome 3q11.2; JBTS9 (OMIM ), caused by mutation in the CC2D2A gene (OMIM ) on chromosome 4p15.3; JBTS10 (OMIM ), caused by mutation in the CXORF5 gene (OMIM ) on chromosome Xp22.3; JBTS11 (see {613820}), caused by mutation in the TTC21B gene (OMIM ) on chromosome 2q24; JBTS12 (see {200990}), caused by mutation in the KIF7 gene (OMIM ) on chromosome 15q26; JBTS13 (OMIM ), caused by mutation in the TCTN1 gene (OMIM ) on chromosome 12q24; JBTS14 (OMIM ), caused by mutation in the TMEM237 gene (OMIM ) on chromosome 2q33; JBTS15 (OMIM ), caused by mutation in the CEP41 gene (OMIM ) on chromosome 7q32; JBTS16 (OMIM ), caused by mutation in the TMEM138 gene (OMIM ) on chromosome 11q; JBTS17 (OMIM ), caused by mutation in the C5ORF42 gene (OMIM ) on chromosome 5p13; JBTS18 (OMIM ), caused by mutation in the TCTN3 gene (OMIM ) on chromosome 10q24; JBTS19 (see {614844}), caused by mutation in the ZNF423 gene (OMIM ) on chromosome 16q12; JBTS20 (OMIM ), caused by mutation in the TMEM231 gene (OMIM ) on chromosome 16q23; JBTS21 (OMIM ), caused by mutation in the CSPP1 gene (OMIM ) on chromosome 8q13; JBTS22 (OMIM ), caused by mutation in the PDE6D gene (OMIM ) on chromosome 2q37; JBTS23 (OMIM ), caused by mutation in the KIAA0586 gene (OMIM ) on chromosome 14q23; JBTS24 (OMIM ), caused by mutation in the TCTN2 gene (OMIM ) on chromosome 12q24; JBTS25 (OMIM ), caused by mutation in the CEP104 gene (OMIM ) on chromosome 1p36; JBTS26 (OMIM ), caused by mutation in the KIAA0556 gene (OMIM ) on chromosome 16p12; JBTS27 (OMIM ), caused by mutation in the B9D1 gene (OMIM ) on chromosome 17p11; JBTS28 (OMIM ), caused by mutation in the MKS1 gene (OMIM ) on chromosome 17q23; JBTS29 (see {617562}), caused by mutation in the TMEM107 gene (OMIM ) on chromosome 17p13; JBTS30 (OMIM ), caused by mutation in the ARMC9 gene (OMIM ) on chromosome 2q37; JBTS31 (OMIM ), caused by mutation in the CEP120 gene (OMIM ) on chromosome 5q23; JBTS32 (OMIM ), caused by mutation in the SUFU gene (OMIM ) on chromosome 10q24; and JBTS33 (OMIM ), caused by mutation in the PIBF1 gene (OMIM ) on chromosome 13q21.

JOUBERT SYNDROME 1; JBTS1 Is also known as joubert syndrome;jbts, joubert-boltshauser syndrome, cerebelloparenchymal disorder iv;cpd4, cerebellooculorenal syndrome 1;cors1;cpd iv; cerebelloparenchymal disorder iv; classic joubert syndrome; joubert syndrome type a; joubert-boltshauser syndrome; pure joubert syndrome

• Autosomal recessive inheritance
• Intellectual disability
• Seizures
• Global developmental delay
• Generalized hypotonia

SOURCES: OMIM SCTID MONDO ORPHANET DOID

Low match NEPHRONOPHTHISIS 11; NPHP11

• Autosomal recessive inheritance
• Global developmental delay
• Growth delay
• Nystagmus
• Strabismus

SOURCES: OMIM MONDO UMLS DOID

Low match SPINOCEREBELLAR ATAXIA, AUTOSOMAL RECESSIVE 21; SCAR21

Autosomal recessive spinocerebellar ataxia-21 is a neurologic disorder characterized by onset of cerebellar ataxia associated with cerebellar atrophy in early childhood. Affected individuals also have recurrent episodes of liver failure in the first decade, resulting in chronic liver fibrosis, as well as later onset of a peripheral neuropathy. Mild learning disabilities may also occur (summary by Schmidt et al., 2015).

SPINOCEREBELLAR ATAXIA, AUTOSOMAL RECESSIVE 21; SCAR21 Is also known as spinocerebellar ataxia, autosomal recessive 21, with hepatopathy;autosomal recessive spinocerebellar ataxia type 21; scar21

• Autosomal recessive inheritance
• Intellectual disability
• Global developmental delay
• Ataxia
• Motor delay

SOURCES: ORPHANET UMLS DOID MONDO OMIM

Low match JOUBERT SYNDROME 6; JBTS6

Joubert syndrome is an autosomal recessive disorder presenting with psychomotor delay, hypotonia, ataxia, oculomotor apraxia, and neonatal breathing abnormalities. Neuroradiologically, Joubert syndrome is characterized by peculiar malformation of the midbrain-hindbrain junction known as the 'molar tooth sign' (MTS) consisting of cerebellar vermis hypoplasia or aplasia, thick and maloriented superior cerebellar peduncles, and abnormally deep interpeduncular fossa (Romano et al., 2006).For a phenotypic description and a discussion of genetic heterogeneity of Joubert syndrome, see {213300}.

• Autosomal recessive inheritance
• Intellectual disability
• Global developmental delay
• Generalized hypotonia
• Ataxia

SOURCES: MESH DOID OMIM UMLS MONDO

Low match SENIOR-LOKEN SYNDROME 9; SLSN9

Senior-Loken syndrome-9 is an autosomal recessive disorder characterized by early-onset nephronophthisis and pigmentary retinopathy. Additional more variable features can include liver defects, skeletal anomalies, and obesity (summary by Bizet et al., 2015).For a phenotypic description and a discussion of genetic heterogeneity of Senior-Loken syndrome, see {266900}.

• Autosomal recessive inheritance
• Global developmental delay
• Nystagmus
• Strabismus
• Abnormality of the skeletal system

SOURCES: OMIM MONDO UMLS

Low match MENTAL RETARDATION, ENTEROPATHY, DEAFNESS, PERIPHERAL NEUROPATHY, ICHTHYOSIS, AND KERATODERMA; MEDNIK

MEDNIK syndrome, previously known as Erythrokeratodermia Variabilis type 3 (EKV3), is characterized by intellectual deficit, enteropathy, sensorineural hearing loss, peripheral neuropathy, lamellar and erythrodermic ichthyosis, and keratodermia (MEDNIK stands for Mental retardation, Enteropathy, Deafness, peripheral Neuropathy, Ichtyosis, Keratodermia).

MENTAL RETARDATION, ENTEROPATHY, DEAFNESS, PERIPHERAL NEUROPATHY, ICHTHYOSIS, AND KERATODERMA; MEDNIK Is also known as erythrokeratodermia variabilis 3;ekv3, erythrokeratodermia variabilis, kamouraska type;intellectual disability-enteropathy-deafness-peripheral neuropathy-ichthyosis-keratodermia syndrome

• Autosomal recessive inheritance
• Intellectual disability
• Global developmental delay
• Generalized hypotonia
• Pica

SOURCES: MESH DOID MONDO ORPHANET OMIM SCTID UMLS