Micrognathia, and Hepatosplenomegaly

Macrocephaly-developmental delay syndrome is a rare, intellectual disability syndrome characterized by macrocephaly, mild dysmorphic features (frontal bossing, long face, hooded eye lids with small, downslanting palpebral fissures, broad nasal bridge, and prominent chin), global neurodevelopmental delay, behavioral abnormalities (e.g. anxiety, stereotyped movements) and absence or generalized tonic-clonic seizures. Additional features reported in some patients include craniosynostosis, fifth finger clinodactyly, recurrent pneumonia, and hepatosplenomegaly.

• Intellectual disability
• Seizures
• Global developmental delay
• Generalized hypotonia
• High palate

SOURCES: ORPHANET OMIM MENDELIAN

Autosomal recessive polycystic kidney disease (ARPKD) is an inherited disorder characterised by the development of cysts affecting the collecting ducts. It is frequently associated with hepatic involvement.

AUTOSOMAL RECESSIVE POLYCYSTIC KIDNEY DISEASE Is also known as polycystic kidney and hepatic disease 1|polycystic kidney disease, infantile, type i|pkhd1|arpkd|ar-pkd|polycystic kidney disease, autosomal recessive|polycystic kidney disease 4 with or without hepatic disease|pkd3, formerly

• Micrognathia
• Hypertension
• Hepatomegaly
• Ventricular septal defect
• Respiratory insufficiency

SOURCES: OMIM ORPHANET MENDELIAN

FGFR2-related bent bone dysplasia is a rare, genetic, lethal, primary bone dysplasia characterized by dysmorphic craniofacial features (low-set, posteriorly rotated ears, hypertelorism, megalophtalmos, flattened and hypoplastic midface, micrognathia), hypomineralization of the calvarium, craniosynostosis, hypoplastic clavicles and pubis, and bent long bones (particularly involving the femora), caused by germline mutations in the FGFR2 gene. Prematurely erupted fetal teeth, osteopenia, hirsutism, clitoromegaly, gingival hyperplasia, and hepatosplenomegaly with extramedullary hematopoesis may also be associated.

FGFR2-RELATED BENT BONE DYSPLASIA Is also known as perinatal lethal bent bone dysplasia

• Hypertelorism
• Micrognathia
• Abnormal facial shape
• Low-set ears
• Brachydactyly

SOURCES: ORPHANET OMIM MENDELIAN

ALG1-CDG is a severe form of congenital disorders of N-linked glycosylation characterized by severe developmental and psychomotor delay, muscular hypotonia, intractable early-onset seizures, and microcephaly. Additional features include altered blood coagulation with a high probability of hemorrhages or thromboses, nephrotic syndrome, ascites, hepatomegaly, cardiomyopathy, ocular manifestations (strabismus, nystagmus), and immunodeficiency. The disease is caused by loss-of-function mutations in the gene ALG1 (16p13.3).

ALG1-CDG Is also known as cdg1k|cdgik|cdg syndrome type ik|congenital disorder of glycosylation type 1k|cdg-ik|mannosyltransferase 1 deficiency|cdg ik|congenital disorder of glycosylation type ik|carbohydrate deficient glycoprotein syndrome type ik

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

SOURCES: MESH ORPHANET OMIM MENDELIAN

Pycnodysostosis is a genetic lysosomal disease characterized by osteosclerosis of the skeleton, short stature and brittle bones.

PYCNODYSOSTOSIS Is also known as pyknodysostosis|pycd|pknd

• Short stature
• Scoliosis
• Micrognathia
• Pain
• Cognitive impairment

SOURCES: OMIM ORPHANET MESH MENDELIAN

COG7-CDG is a congenital disorder of glycosylation characterised by dysmorphism, skeletal dysplasia, hypotonia, hepatosplenomegaly, jaundice, cardiac insufficiency, recurrent infections and epilepsy. To date, it has been described in two infants, both of whom died within the first three months of life. The syndrome is caused by a mutation in the gene encoding COG-7 (chromosome 16), a subunit of the oligomeric Golgi complex.

COG7-CDG Is also known as carbohydrate deficient glycoprotein syndrome type iie|congenital disorder of glycosylation type 2e|cdg iie|cdg syndrome type iie|cdg2e|congenital disorder of glycosylation type iie|cdg-iie|cdgiie

• Seizures
• Global developmental delay
• Generalized hypotonia
• Microcephaly
• Growth delay

SOURCES: OMIM ORPHANET MESH MENDELIAN

The peroxisomal biogenesis disorder (PBD) Zellweger syndrome (ZS) is an autosomal recessive multiple congenital anomaly syndrome. Affected children present in the newborn period with profound hypotonia, seizures, and inability to feed. Characteristic craniofacial anomalies, eye abnormalities, neuronal migration defects, hepatomegaly, and chondrodysplasia punctata are present. Children with this condition do not show any significant development and usually die in the first year of life (summary by Steinberg et al., 2006).For a complete phenotypic description and a discussion of genetic heterogeneity of Zellweger syndrome, see {214100}.Individuals with PBDs of complementation group 5 (CG5, equivalent to CG10 and CGF) have mutations in the PEX2 gene. For information on the history of PBD complementation groups, see {214100}.

• Intellectual disability
• Seizures
• Global developmental delay
• Generalized hypotonia
• Hypertelorism

SOURCES: OMIM MENDELIAN

Congenital intrauterine infection-like syndrome is characterised by the presence of microcephaly and intracranial calcifications at birth accompanied by neurological delay, seizures and a clinical course similar to that seen in patients after intrauterine infection with Toxoplasma gondii, Rubella, Cytomegalovirus, Herpes simplex (so-called TORCH syndrome), or other agents, despite repeated tests revealing the absence of any known infectious agent.

CONGENITAL INTRAUTERINE INFECTION-LIKE SYNDROME Is also known as baraitser-reardon syndrome|bilateral band-like calcification with polymicrogyria|blc-pmg|blcpmg|band-like calcification with simplified gyration and polymicrogyria|microcephaly-intracranial calcification-intellectual disability syndrome|pseudo-torch syndr

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

SOURCES: ORPHANET OMIM MENDELIAN

Prolidase deficiency is an inherited disorder of peptide metabolism characterized by severe skin lesions, recurrent infections (involving mainly the skin and respiratory system), dysmorphic facial features, variable cognitive impairment, and splenomegaly.

PROLIDASE DEFICIENCY Is also known as hyperimidodipeptiduria

• Intellectual disability
• Global developmental delay
• Hearing impairment
• Hypertelorism
• Micrognathia

SOURCES: ORPHANET MESH OMIM MENDELIAN

Greenberg dysplasia is a very rare lethal skeletal dysplasia characterized by fetal hydrops, short limbs and abnormal chondro-osseous calcification. The disease is characterized by early in utero lethality and affected fetuses are considered as nonviable.

GREENBERG DYSPLASIA Is also known as skeletal dysplasia, greenberg type|hem dysplasia|moth-eaten skeletal dysplasia|hem skeletal dysplasia|hydrops-ectopic calcification-motheaten syndrome|hydrops-ectopic calcification-moth-eaten skeletal dysplasia|chondrodystrophy, hydropic and prenatally le

• Hypertelorism
• Micrognathia
• Low-set ears
• Depressed nasal bridge
• Hepatomegaly

SOURCES: ORPHANET OMIM MESH MENDELIAN