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Intellectual developmental disorder with speech delay and axonal peripheral neuropathy(IDDSAPN)

MedGen UID:
1754849
Concept ID:
C5436813
Disease or Syndrome
Synonyms: IDDSAPN; INTELLECTUAL DEVELOPMENTAL DISORDER WITH SPEECH DELAY AND AXONAL PERIPHERAL NEUROPATHY
 
Gene (location): NEMF (14q21.3)
 
Monarch Initiative: MONDO:0030849
OMIM®: 619099

Definition

Intellectual developmental disorder with speech delay and axonal peripheral neuropathy (IDDSAPN) is an autosomal recessive neurologic disorder characterized by mild global developmental delay with motor impairment and severe speech delay apparent in the first years of life. Affected individuals begin to walk independently between 3 and 4 years of age, but often have an unsteady or ataxic gait. Most patients have progressive distal muscle weakness and atrophy of the lower limbs, foot or hand deformities, and dysarthria, consistent with a peripheral neuropathy. There is mildly impaired intellectual development. Some patients may have behavioral anomalies, such as autistic features or attention deficit-hyperactivity disorder (ADHD), and some can attend special schools. The overall clinical features indicate involvement of both the central and peripheral nervous systems (summary by Martin et al., 2020 and Ahmed et al., 2021) [from OMIM]

Clinical features

From HPO
Cerebellar ataxia
MedGen UID:
849
Concept ID:
C0007758
Disease or Syndrome
Cerebellar ataxia refers to ataxia due to dysfunction of the cerebellum. This causes a variety of elementary neurological deficits including asynergy (lack of coordination between muscles, limbs and joints), dysmetria (lack of ability to judge distances that can lead to under- or overshoot in grasping movements), and dysdiadochokinesia (inability to perform rapid movements requiring antagonizing muscle groups to be switched on and off repeatedly).
Tremor
MedGen UID:
21635
Concept ID:
C0040822
Sign or Symptom
An unintentional, oscillating to-and-fro muscle movement about a joint axis.
Delayed speech and language development
MedGen UID:
105318
Concept ID:
C0454644
Finding
A degree of language development that is significantly below the norm for a child of a specified age.
Global developmental delay
MedGen UID:
107838
Concept ID:
C0557874
Finding
A delay in the achievement of motor or mental milestones in the domains of development of a child, including motor skills, speech and language, cognitive skills, and social and emotional skills. This term should only be used to describe children younger than five years of age.
Peripheral axonal neuropathy
MedGen UID:
266071
Concept ID:
C1263857
Disease or Syndrome
An abnormality characterized by disruption of the normal functioning of peripheral axons.
Intellectual disability
MedGen UID:
811461
Concept ID:
C3714756
Mental or Behavioral Dysfunction
Intellectual disability, previously referred to as mental retardation, is characterized by subnormal intellectual functioning that occurs during the developmental period. It is defined by an IQ score below 70.
Kyphoscoliosis
MedGen UID:
154361
Concept ID:
C0575158
Anatomical Abnormality
An abnormal curvature of the spine in both a coronal (lateral) and sagittal (back-to-front) plane.
Distal amyotrophy
MedGen UID:
338530
Concept ID:
C1848736
Disease or Syndrome
Muscular atrophy affecting muscles in the distal portions of the extremities.
Generalized hypotonia
MedGen UID:
346841
Concept ID:
C1858120
Finding
Generalized muscular hypotonia (abnormally low muscle tone).
Respiratory distress
MedGen UID:
96907
Concept ID:
C0476273
Sign or Symptom
Respiratory distress is objectively observable as the physical or emotional consequences from the experience of dyspnea. The physical presentation of respiratory distress is generally referred to as labored breathing, while the sensation of respiratory distress is called shortness of breath or dyspnea.

Recent clinical studies

Etiology

Efthymiou S, Salpietro V, Malintan N, Poncelet M, Kriouile Y, Fortuna S, De Zorzi R, Payne K, Henderson LB, Cortese A, Maddirevula S, Alhashmi N, Wiethoff S, Ryten M, Botia JA, Provitera V, Schuelke M, Vandrovcova J; SYNAPS Study Group, Walsh L, Torti E, Iodice V, Najafi M, Karimiani EG, Maroofian R, Siquier-Pernet K, Boddaert N, De Lonlay P, Cantagrel V, Aguennouz M, El Khorassani M, Schmidts M, Alkuraya FS, Edvardson S, Nolano M, Devaux J, Houlden H
Brain 2019 Oct 1;142(10):2948-2964. doi: 10.1093/brain/awz248. PMID: 31501903Free PMC Article

Diagnosis

Madrid R, Guariglia SR, Haworth A, Korosh W, Gavin M, Lyon GJ
Cold Spring Harb Mol Case Stud 2020 Jun;6(3) Epub 2020 Jun 12 doi: 10.1101/mcs.a005108. PMID: 32532879Free PMC Article

Clinical prediction guides

Efthymiou S, Salpietro V, Malintan N, Poncelet M, Kriouile Y, Fortuna S, De Zorzi R, Payne K, Henderson LB, Cortese A, Maddirevula S, Alhashmi N, Wiethoff S, Ryten M, Botia JA, Provitera V, Schuelke M, Vandrovcova J; SYNAPS Study Group, Walsh L, Torti E, Iodice V, Najafi M, Karimiani EG, Maroofian R, Siquier-Pernet K, Boddaert N, De Lonlay P, Cantagrel V, Aguennouz M, El Khorassani M, Schmidts M, Alkuraya FS, Edvardson S, Nolano M, Devaux J, Houlden H
Brain 2019 Oct 1;142(10):2948-2964. doi: 10.1093/brain/awz248. PMID: 31501903Free PMC Article

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